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Sample records for immunodeficiency virus dna

  1. Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine

    SciTech Connect

    Sparger, Ellen E. Dubie, Robert A.; Shacklett, Barbara L.; Cole, Kelly S.; Chang, W.L.; Luciw, Paul A.

    2008-05-10

    Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-{gamma} enzyme-linked immunospot responses of low magnitude were observed after immunization with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by twenty weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus.

  2. Human Immunodeficiency Virus Integration Protein Expressed in Escherichia Coli Possesses Selective DNA Cleaving Activity

    NASA Astrophysics Data System (ADS)

    Sherman, Paula A.; Fyfe, James A.

    1990-07-01

    The human immunodeficiency virus (HIV) integration protein, a potential target for selective antiviral therapy, was expressed in Escherichia coli. The purified protein, free of detectable contaminating endonucleases, selectively cleaved double-stranded DNA oligonucleotides that mimic the U3 and the U5 termini of linear HIV DNA. Two nucleotides were removed from the 3' ends of both the U5 plus strand and the U3 minus strand; in both cases, cleavage was adjacent to a conserved CA dinucleotide. The reaction was metal-ion dependent, with a preference for Mn2+ over Mg2+. Reaction selectivity was further demonstrated by the lack of cleavage of an HIV U5 substrate on the complementary (minus) strand, an analogous substrate that mimics the U3 terminus of an avian retrovirus, and an HIV U5 substrate in which the conserved CA dinucleotide was replaced with a TA dinucleotide. Such an integration protein-mediated cleavage reaction is expected to occur as part of the integration event in the retroviral life cycle, in which a double-stranded DNA copy of the viral RNA genome is inserted into the host cell DNA.

  3. Detection of human immunodeficiency virus DNA and RNA in semen by the polymerase chain reaction.

    PubMed

    Mermin, J H; Holodniy, M; Katzenstein, D A; Merigan, T C

    1991-10-01

    Peripheral blood mononuclear cells (PBMC) and semen of 23 men infected with human immunodeficiency virus (HIV) were examined for the presence of HIV DNA and RNA using the polymerase chain reaction (PCR) and a nonisotopic detection assay. None of the men was receiving antiretroviral therapy at the time of collection. Semen samples were separated into cell-free seminal fluid, nonspermatozoal mononuclear cells (NSMC), and spermatozoa. All of the PBMC samples, 17 (74%) of 23 NSMC samples, and none of the spermatozoal samples were positive for HIV gag gene DNA. Of 23 cell-free seminal fluid samples, 15 (65%) were positive for HIV gag gene RNA by PCR. Cell-free HIV RNA was more likely to be present in the semen of men with less than 400 than in those with greater than or equal to 400 cells/mm3 (P less than .04) and was present in all patient with p24 antigen in serum. The presence of HIV DNA in NSMC samples was not related to CD4 cell count, disease status, or the presence of p24 antigen in the serum. This study shows that HIV nucleic acid can be detected by PCR in either the cell-free seminal fluid or NSMC of 87% of semen samples but not in the DNA of spermatozoa from HIV-infected men.

  4. Chemokine Adjuvanted Electroporated-DNA Vaccine Induces Substantial Protection from Simian Immunodeficiency Virus Vaginal Challenge

    PubMed Central

    Hutnick, N A; Moldoveanu, Z; Hunter, M; Reuter, M; Yuan, S; Yan, J; Ginsberg, A; Sylvester, A; Pahar, B; Carnathan, D; Kathuria, N; Khan, A S; Montefiori, D; Sardesai, N Y; Betts, M R; Mestecky, J; Marx, P; Weiner, D B

    2015-01-01

    There have been encouraging results for the development of an effective HIV vaccine. However, many questions remain regarding the quality of immune responses and the role of mucosal antibodies. We addressed some of these issues by using a simian immunodeficiency virus (SIV) DNA vaccine adjuvanted with plasmid-expressed mucosal chemokines combined with an intravaginal SIV challenge in rhesus macaque (RhM) model. We previously reported on the ability of CCR9 and CCR10 ligand (L) adjuvants to enhance mucosal and systemic IgA and IgG in small animals. In this study, RhMs were intramuscularly immunized five times with either DNA or DNA plus chemokine adjuvant delivered by electroporation followed by challenge with SIVsmE660. Sixty-eight percent of all vaccinated animals (P=0.0016) remained either uninfected or had aborted infection compared to only 14% in the vaccine naïve group. The highest protection was observed in the CCR10L chemokines group, where 6 of 9 animals had aborted infection and two remained uninfected, leading to 89% protection (P=0.0003). The induction of mucosal SIV-specific antibodies and neutralization titers correlated with trends in protection. These results indicate the need to further investigate the contribution of chemokine adjuvants to modulate immune responses and the role of mucosal antibodies in SIV/HIV protection. PMID:25943275

  5. Testing for Human Immunodeficiency Virus

    MedlinePlus

    ... incisions made in the mother’s abdomen and uterus. Human Immunodeficiency Virus (HIV): A virus that attacks certain cells of the body’s immune system and causes acquired immunodeficiency syndrome (AIDS). Immune System: ...

  6. Human Immunodeficiency Virus Type 1 Vpr Induces DNA Replication Stress In Vitro and In Vivo▿

    PubMed Central

    Zimmerman, Erik S.; Sherman, Michael P.; Blackett, Jana L.; Neidleman, Jason A.; Kreis, Christophe; Mundt, Pamela; Williams, Samuel A.; Warmerdam, Maria; Kahn, James; Hecht, Frederick M.; Grant, Robert M.; de Noronha, Carlos M. C.; Weyrich, Andrew S.; Greene, Warner C.; Planelles, Vicente

    2006-01-01

    The human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) causes cell cycle arrest in G2. Vpr-expressing cells display the hallmarks of certain forms of DNA damage, specifically activation of the ataxia telangiectasia mutated and Rad3-related kinase, ATR. However, evidence that Vpr function is relevant in vivo or in the context of viral infection is still lacking. In the present study, we demonstrate that HIV-1 infection of primary, human CD4+ lymphocytes causes G2 arrest in a Vpr-dependent manner and that this response requires ATR, as shown by RNA interference. The event leading to ATR activation in CD4+ lymphocytes is the accumulation of replication protein A in nuclear foci, an indication that Vpr likely induces stalling of replication forks. Primary macrophages are refractory to ATR activation by Vpr, a finding that is consistent with the lack of detectable ATR, Rad17, and Chk1 protein expression in these nondividing cells. These observations begin to explain the remarkable resilience of macrophages to HIV-1-induced cytopathicity. To study the in vivo consequences of Vpr function, we isolated CD4+ lymphocytes from HIV-1-infected individuals and interrogated the cell cycle status of anti-p24Gag-immunoreactive cells. We report that infected cells in vivo display an aberrant cell cycle profile whereby a majority of cells have a 4N DNA content, consistent with the onset of G2 arrest. PMID:16956949

  7. Epstein-Barr virus DNA loads in adult human immunodeficiency virus type 1-infected patients receiving highly active antiretroviral therapy

    NASA Technical Reports Server (NTRS)

    Ling, Paul D.; Vilchez, Regis A.; Keitel, Wendy A.; Poston, David G.; Peng, Rong Sheng; White, Zoe S.; Visnegarwala, Fehmida; Lewis, Dorothy E.; Butel, Janet S.

    2003-01-01

    Patients with human immunodeficiency virus type 1 (HIV-1) infection are at high risk of developing Epstein-Barr virus (EBV)-associated lymphoma. However, little is known of the EBV DNA loads in patients receiving highly active antiretroviral therapy (HAART). Using a real-time quantitative polymerase chain reaction assay, we demonstrated that significantly more HIV-1-infected patients receiving HAART than HIV-1-uninfected volunteers had detectable EBV DNA in blood (57 [81%] of 70 vs. 11 [16%] of 68 patients; P=.001) and saliva (55 [79%] of 68 vs. 37 [54%] of 68 patients; P=.002). The mean EBV loads in blood and saliva samples were also higher in HIV-1-infected patients than in HIV-1-uninfected volunteers (P=.001). The frequency of EBV detection in blood was associated with lower CD4+ cell counts (P=.03) among HIV-1-infected individuals, although no differences were observed in the EBV DNA loads in blood or saliva samples in the HIV-1-infected group. Additional studies are needed to determine whether EBV-specific CD4+ and CD8+ cells play a role in the pathogenesis of EBV in HIV-1-infected patients receiving HAART.

  8. Human Immunodeficiency Virus Prevention.

    PubMed

    Davis, Teaniese Latham; DiClemente, Ralph

    2016-04-01

    Human immunodeficiency virus (HIV) is the virus that causes AIDS. Surveillance data from 2012 indicate an estimated 1.2 million people aged 13 years and older were living with HIV infection in the United States, and 12.8% do not know their status. There are approximately 50,000 new HIV infections annually. With no available cure for HIV, primary prevention to reduce incident cases of HIV is essential. Strategies to prevent HIV transmission include reducing sexual risk behavior and needle sharing. The Centers for Disease Control and Prevention has multiple resources available for primary and secondary prevention to reduce disease transmission and severity. PMID:26980130

  9. Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: Evidence for differential gene expression

    SciTech Connect

    Kim, Sunyoung; Baltimore, D. Massachusetts Institute of Technology, Cambridge ); Byrn, R.; Groopman, J. )

    1989-09-01

    The kinetics of retroviral DNA and RNA synthesis are parameters vital to understanding viral growth, especially for human immunodeficiency virus (HIV), which encodes several of its own regulatory genes. The authors have established a single-cycle growth condition for HIV in H9 cells, a human CD4{sup +} lymphocyte line. The full-length viral linear DNA is first detectable by 4 h postinfection. During a one-step growth of HIV, amounts of viral DNA gradually increase until 8 to 12 h postinfection and then decrease. The copy number of unintegrated viral DNA is not extraordinarily high even at its peak. Most strikingly, there is a temporal program of RNA accumulation: the earliest RNA is greatly enriched in the 2-kilobase subgenomic mRNA species, while the level of 9.2-kilobase RNA which is both genomic RNA and mRNA remains low until after 24 h of infection. Virus production begins at about 24 h postinfection. Thus, viral DNA synthesis is as rapid as for other retroviruses, but viral RNA synthesis involves temporal alteration in the species that accumulate, presumably as a consequence of viral regulatory genes.

  10. Activities of Human Immunodeficiency Virus (HIV) Integration Protein In vitro: Specific Cleavage and Integration of HIV DNA

    NASA Astrophysics Data System (ADS)

    Bushman, Frederic D.; Craigie, Robert

    1991-02-01

    Growth of human immunodeficiency virus (HIV) after infection requires the integration of a DNA copy of the viral RNA genome into a chromosome of the host. Here we present a simple in vitro system that carries out the integration reaction and the use of this system to probe the mechanism of integration. The only HIV protein necessary is the integration (IN) protein, which has been overexpressed in insect cells and then partially purified. DNA substrates are supplied as oligonucleotides that match the termini of the linear DNA product of reverse transcription. In the presence of HIV IN protein, oligonucleotide substrates are cleaved to generate the recessed 3' ends that are the precursor for integration, and the cleaved molecules are efficiently inserted into a DNA target. Analysis of reaction products reveals that HIV IN protein joins 3' ends of the viral DNA to 5' ends of cuts made by IN protein in the DNA target. We have also used this assay to characterize the sequences at the ends of the viral DNA involved in integration. The assay provides a simple screen for testing candidate inhibitors of HIV IN protein; some such inhibitors might have useful antiviral activity.

  11. Ultrastructural characteristics and DNA immunocytochemistry in human immunodeficiency virus and zidovudine-associated myopathies.

    PubMed

    Pezeshkpour, G; Illa, I; Dalakas, M C

    1991-12-01

    Electron microscopic features of muscle biopsies from 13 human immunodeficiency (HIV)-positive patients who had myopathy while receiving zidovudine (AZT) were compared with biopsies from five patients with HIV-induced myopathy who were not treated with AZT. All specimens showed disorganization of the myofibrillar structures, along with a varying degree of nemaline (rod) bodies, vacuolization, inflammation, and endothelial tubuloreticular profiles. One untreated and all AZT-treated patients had cytoplasmic bodies, which in the latter were abundant, large, and irregular. Two untreated patients had a peculiar osmiophilic destruction of the muscle fibers, with numerous tubuloreticular profiles in the endothelial cells and brisk inflammation that included lymphoplasmatoid cells. The AZT-treated group had ubiquitous abnormal mitochondria that complemented the presence of ragged red fibers seen by light microscopy. There was subsarcolemmal proliferation of mitochondria, with marked variation in size and shape and proliferation or disorganization of their cristae. Paracrystalline inclusions were seen in one patient. Blind re-examination of the electron micrographs showed abnormal mitochondria that readily distinguished patients with AZT-associated myopathy from those with untreated HIV-induced myopathy. Immunocytochemistry using antibodies to single- and double-stranded DNA revealed severe reduction of mitochondrial DNA compared with the normal nuclear DNA. Although the myopathies associated with HIV and AZT share common myopathologic features, the mitochondrial abnormalities are unique to the AZT-treated patients. Since mitochondrial DNA is specifically reduced, the structural changes noted on electron microscopy are probably associated with mitochondrial dysfunction. Zidovudine, a DNA chain terminator that inhibits the mitochondrial gamma-DNA polymerase, is toxic to muscle mitochondria.

  12. Detection of DNA of Lymphotropic Herpesviruses in Plasma of Human Immunodeficiency Virus-Infected Patients: Frequency and Clinical Significance

    PubMed Central

    Broccolo, Francesco; Bossolasco, Simona; Careddu, Anna M.; Tambussi, Giuseppe; Lazzarin, Adriano; Cinque, Paola

    2002-01-01

    The frequency and clinical significance of detection of DNA of cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), HHV-7, and HHV-8 in plasma were investigated by PCR. The plasma was obtained from 120 selected human immunodeficiency virus (HIV)-infected patients, of whom 75 had AIDS-related manifestations, 32 had primary HIV infection (PHI), and 13 had asymptomatic infections. Nested PCR analysis revealed that none of the lymphotropic herpesviruses tested were found in patients with PHI, in asymptomatic HIV-positive individuals, or in HIV-negative controls. By contrast, DNA of one or more of the viruses was found in 42 (56%) of 75 patients with AIDS-related manifestations, including CMV disease (CMV-D) or AIDS-related tumors. The presence of CMV DNA in plasma was significantly associated with CMV-D (P < 0.001). By contrast, EBV detection was not significantly associated with AIDS-related lymphomas (P = 0.31). Interestingly, the presence of HHV-8 DNA in plasma was significantly associated with Kaposi's sarcoma (KS) disease (P < 0.001) and with the clinical status of KS patients (P < 0.001). CMV (primarily), EBV, and HHV-8 were the viruses most commonly reactivated in the context of severe immunosuppression (P < 0.05). In contrast, HHV-6 and HHV-7 infections were infrequent at any stage of disease. In conclusion, plasma PCR was confirmed to be useful in the diagnosis of CMV-D but not in that of tumors or other conditions possibly associated with EBV, HHV-6, and HHV-7. Our findings support the hypothesis of a direct involvement of HHV-8 replication in KS pathogenesis, thus emphasizing the usefulness of sensitive and specific diagnostic tests to monitor HHV-8 infection. PMID:12414753

  13. Human Immunodeficiency Virus (HIV) Primary Infection

    MedlinePlus

    ... rashes clinical tools newsletter | contact Share | Human Immunodeficiency Virus (HIV) Primary Infection Information for adults A A ... weeks following exposure to HIV (the human immunodeficiency virus). Chronic infection with this virus can cause AIDS ( ...

  14. Incomplete removal of the RNA primer for minus-strand DNA synthesis by human immunodeficiency virus type 1 reverse transcriptase.

    PubMed Central

    Pullen, K A; Ishimoto, L K; Champoux, J J

    1992-01-01

    A synthetic RNA oligonucleotide (15-mer) corresponding to the 3' end of the lysine tRNA primer was hybridized to single-stranded DNA containing the human immunodeficiency virus type 1 (HIV-1) primer-binding site and extended with a DNA polymerase. The resulting structures were used to study primer removal by the RNase H activity of HIV-1 reverse transcriptase. The initial cleavage event removes the RNA primer as a 14-mer and leaves a single ribonucleotide A residue bound to the 5' end of the DNA strand. This result explains the observation by several groups that HIV-1 circle junctions contain 4 bp that are not present in the integrated provirus instead of the predicted 3 bp. Subsequent cleavage events occur at other sites internal to the RNA molecule, and the ribonucleotide A residue on the end of the DNA strand is ultimately removed. Therefore, the biologically relevant cleavage that produces the 14-mer reflects the kinetics of the reaction as well as a specificity for nucleic acid sequence. When the RNA oligonucleotide alone was hybridized to the primer-binding site and tested as a substrate for HIV-1 RNase H, the cleavage pattern near the 3' end of the RNA was altered. Images PMID:1370087

  15. Efficient Gap Repair Catalyzed In Vitro by an Intrinsic DNA Polymerase Activity of Human Immunodeficiency Virus Type 1 Integrase

    PubMed Central

    Acel, Andrea; Udashkin, Brian E.; Wainberg, Mark A.; Faust, Emmanuel A.

    1998-01-01

    Cleavage and DNA joining reactions, carried out by human immunodeficiency virus type 1 (HIV-1) integrase, are necessary to effect the covalent insertion of HIV-1 DNA into the host genome. For the integration of HIV-1 DNA into the cellular genome to be completed, short gaps flanking the integrated proviral DNA must be repaired. It has been widely assumed that host cell DNA repair enzymes are involved. Here we report that HIV-1 integrase multimers possess an intrinsic DNA-dependent DNA polymerase activity. The activity was characterized by its dependence on Mg2+, resistance to N-ethylmaleimide, and inhibition by 3′-azido-2′,3′-dideoxythymidine-5′-triphosphate, coumermycin A1, and pyridoxal 5′-phosphate. The enzyme efficiently utilized poly(dA)-oligo(dT) or self-annealing oligonucleotides as a template primer but displayed relatively low activity with gapped calf thymus DNA and no activity with poly(dA) or poly(rA)-oligo(dT). A monoclonal antibody binding specifically to an epitope comprised of amino acids 264 to 273 near the C terminus of HIV-1 integrase severely inhibited the DNA polymerase activity. A deletion of 50 amino acids at the C terminus of integrase drastically altered the gel filtration properties of the DNA polymerase, although the level of activity was unaffected by this mutation. The DNA polymerase efficiently extended a hairpin DNA primer up to 19 nucleotides on a T20 DNA template, although addition of the last nucleotide occurred infrequently or not at all. The ability of integrase to repair gaps in DNA was also investigated. We designed a series of gapped molecules containing a single-stranded region flanked by a duplex U5 viral arm on one side and by a duplex nonviral arm on the other side. Molecules varied structurally depending on the size of the gap (one, two, five, or seven nucleotides), their content of T’s or C’s in the single-stranded region, whether the CA dinucleotide in the viral arm had been replaced with a nonviral

  16. The trans-inhibitory Rep78 protein of adeno-associated virus binds to TAR region DNA of the human immunodeficiency virus type 1 long terminal repeat.

    PubMed

    Batchu, R B; Hermonat, P L

    1995-07-01

    The large rep gene products, Rep78 and Rep68, of adeno-associated virus (AAV) are pleiotropic effector proteins which are required for AAV DNA replication and the trans-regulation of AAV gene expression. Apart from these essential functions prerequisite for the life cycle of AAV, these rep products are able to inhibit the replication and gene expression of human immunodeficiency virus type 1 (HIV-1) and a number of DNA viruses. Here, it is demonstrated that Rep78, as a chimeric with the maltose binding protein, directly binds the full-length HIV-1 long terminal repeat (LTR), and to a subset of these sequences containing the trans-activation response (TAR) sequence as DNA. These interactions, an effector protein physically binding a target promoter, suggest a direct mechanism of action for Rep78 inhibition. Furthermore, competitive binding studies between the TAR region and the full-length HIV-LTR, strongly suggested that another site(s) within the LTR was also bound by Rep78. Finally, as Rep78 binding is also believed to be affected by secondary structure within the DNA, it was found that Rep78 preferentially binds with HIV-LTR sequences with promoted secondary structure generated by heat denaturation and rapid cooling.

  17. Quantitative analysis of RNA cleavage during RNA-directed DNA synthesis by human immunodeficiency and avian myeloblastosis virus reverse transcriptases.

    PubMed Central

    DeStefano, J J; Mallaber, L M; Fay, P J; Bambara, R A

    1994-01-01

    We have determined the extent of RNA cleavage carried out during DNA synthesis by either human immunodeficiency virus (HIV) or avian myeloblastosis virus (AMV) reverse transcriptases (RTs). Conditions were chosen that allowed the analysis of the cleavage and synthesis performed by the RT during one binding event on a given template-primer. The maximum quantity of ribonuclease H (RNase H) sensitive template RNA left after synthesis by the RTs was determined by treatment with Escherichia coli RNase H. RNA cleavage products that were expected to be too short to remain hybridized, less than 13 nucleotides in length, were quantitated. Results showed that HIV- and AMV-RT degraded about 80% and less than 20%, respectively, of the potentially degradable RNA to these short products. Survival of longer, hybridized RNA was not a result of synthesis by a population of RTs that had selectively lost RNase H activity. Using an assay that evaluated the proportion of primers extended versus RNA templates cleaved during primer-extension by the RTs, we determined that essentially each molecule of HIV- and AMV-RT with polymerase also has RNase H activity. The results indicate that although both HIV- and AMV-RTs cleave the RNA template during synthesis, the number of cleavages per nucleotide addition with HIV-RT is much greater. They also suggest that some hybridized RNA segments remain right after the passage of the RT making the first DNA strand. In vivo, these segments would have to be cleaved or displaced in later reactions before second strand DNA synthesis could be completed. Images PMID:7524028

  18. Rapid Method for Screening Dried Blood Samples on Filter Paper for Human Immunodeficiency Virus Type 1 DNA

    PubMed Central

    Panteleeff, Dana DeVange; John, Grace; Nduati, Ruth; Mbori-Ngacha, Dorothy; Richardson, Barbra; Kreiss, Joan; Overbaugh, Julie

    1999-01-01

    PCR is a highly sensitive method for the detection of human immunodeficiency virus type 1 (HIV-1) nucleic acids in blood mononuclear cells and plasma. However, blood separation techniques require extensive laboratory support systems and are difficult when a limited volume of blood is available, which is often the case for infants. The use of blood samples stored on filter paper has many advantages for the detection of perinatal HIV-1 infection, but current methods require extraction and purification of target DNA prior to PCR amplification. We report a highly sensitive and rapid method for the extraction and detection of HIV-1 DNA in infant blood samples stored on filter papers. Because this rapid protocol does not involve steps for the removal of potential inhibitors of the PCR, the highest sensitivity is achieved by testing the filter paper lysate in quadruplicate. Assays for HIV-1 DNA were done by using nested PCR techniques that amplify HIV-1 gag DNA from blood spot samples on filter paper and from corresponding viably frozen mononuclear cells separated from venous blood samples obtained from 111 infants born to HIV-1-seropositive mothers. PCR results with blood from filter papers showed 100% specificity (95% confidence internal [CI] 93.1 to 100%) and 96% (95% CI, 88.65 to 98.9%) and 88% (95% CI, 79.2 to 94.5%) sensitivity (for quadruplicate and duplicate tests, respectively) compared to PCR results with blood mononuclear cells. Moreover, this method could detect HIV-1 sequences of multiple subtypes. PMID:9889216

  19. The core and carboxyl-terminal domains of the integrase protein of human immunodeficiency virus type 1 each contribute to nonspecific DNA binding.

    PubMed Central

    Engelman, A; Hickman, A B; Craigie, R

    1994-01-01

    The integrase protein of human immunodeficiency virus type 1 removes two nucleotides from the 3' ends of reverse-transcribed human immunodeficiency virus type 1 DNA (3' processing) and covalently inserts the processed ends into a target DNA (DNA strand transfer). Mutant integrase proteins that lack the amino-and/or carboxyl-terminal domains are incapable of catalyzing 3' processing and DNA strand transfer but are competent for an apparent reversal of the DNA strand transfer reaction (disintegration) in vitro. Here, we investigate the binding of integrase to DNA by UV cross-linking. Cross-linked complexes form with a variety of DNA substrates independent of the presence of divalent metal ion. Analysis with amino- and carboxyl-terminal deletion mutant proteins shows that residues 213 to 266 of the 288-residue protein are required for efficient cross-linking in the absence of divalent metal ion. Carboxyl-terminal deletion mutants that lack this region efficiently cross-link only to the branched disintegration DNA substrate, and this reaction is dependent on the presence of metal ion. Both the core and C-terminal domains of integrase therefore contribute to nonspecific DNA binding. Images PMID:8057470

  20. Nonpathogenic Simian Immunodeficiency Virus Infections

    PubMed Central

    Klatt, Nichole R.; Silvestri, Guido; Hirsch, Vanessa

    2012-01-01

    The simian immunodeficiency viruses (SIVs) are a diverse group of viruses that naturally infect a wide range of African primates, including African green monkeys (AGMs) and sooty mangabey monkeys (SMs). Although natural infection is widespread in feral populations of AGMs and SMs, this infection generally does not result in immunodeficiency. However, experimental inoculation of Asian macaques results in an immunodeficiency syndrome remarkably similar to human AIDS. Thus, natural nonprogressive SIV infections appear to represent an evolutionary adaptation between these animals and their primate lentiviruses. Curiously, these animals maintain robust virus replication but have evolved strategies to avoid disease progression. Adaptations observed in these primates include phenotypic changes to CD4+ T cells, limited chronic immune activation, and altered mucosal immunity. It is probable that these animals have achieved a unique balance between T-cell renewal and proliferation and loss through activation-induced apoptosis, and virus-induced cell death. A clearer understanding of the mechanisms underlying the lack of disease progression in natural hosts for SIV infection should therefore yield insights into the pathogenesis of AIDS and may inform vaccine design. PMID:22315718

  1. Human immunodeficiency virus infection and pneumothorax

    PubMed Central

    Terzi, Eirini; Zarogoulidis, Konstantinos; Kougioumtzi, Ioanna; Dryllis, Georgios; Kioumis, Ioannis; Pitsiou, Georgia; Machairiotis, Nikolaos; Katsikogiannis, Nikolaos; Tsiouda, Theodora; Madesis, Athanasios; Karaiskos, Theodoros

    2014-01-01

    Pneumothorax is a serious and relatively frequent complication of human immunodeficiency virus (HIV) infection that may associate with increased morbidity and mortality and may prove difficult to manage, especially in patients with acquired immunodeficiency syndrome (AIDS). PMID:25337392

  2. DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge.

    PubMed

    Patel, Vainav; Jalah, Rashmi; Kulkarni, Viraj; Valentin, Antonio; Rosati, Margherita; Alicea, Candido; von Gegerfelt, Agneta; Huang, Wensheng; Guan, Yongjun; Keele, Brandon F; Bess, Julian W; Piatak, Michael; Lifson, Jeffrey D; Williams, William T; Shen, Xiaoying; Tomaras, Georgia D; Amara, Rama R; Robinson, Harriet L; Johnson, Welkin; Broderick, Kate E; Sardesai, Niranjan Y; Venzon, David J; Hirsch, Vanessa M; Felber, Barbara K; Pavlakis, George N

    2013-02-19

    We have previously shown that macaques vaccinated with DNA vectors expressing SIVmac239 antigens developed potent immune responses able to reduce viremia upon high-dose SIVmac251 challenge. To further improve vaccine-induced immunity and protection, we combined the SIVmac239 DNA vaccine with protein immunization using inactivated SIVmac239 viral particles as protein source. Twenty-six weeks after the last vaccination, the animals were challenged intrarectally at weekly intervals with a titrated dose of the heterologous SIVsmE660. Two of DNA-protein coimmunized macaques did not become infected after 14 challenges, but all controls were infected by 11 challenges. Vaccinated macaques showed modest protection from SIVsmE660 acquisition compared with naïve controls (P = 0.050; stratified for TRIM5α genotype). Vaccinees had significantly lower peak (1.6 log, P = 0.0048) and chronic phase viremia (P = 0.044), with 73% of the vaccinees suppressing viral replication to levels below assay detection during the 40-wk follow-up. Vaccine-induced immune responses associated significantly with virus control: binding antibody titers and the presence of rectal IgG to SIVsmE660 Env correlated with delayed SIVsmE660 acquisition; SIV-specific cytotoxic T cells, prechallenge CD4(+) effector memory, and postchallenge CD8(+) transitional memory cells correlated with control of viremia. Thus, SIVmac239 DNA and protein-based vaccine protocols were able to achieve high, persistent, broad, and effective cellular and humoral immune responses able to delay heterologous SIVsmE660 infection and to provide long-term control of viremia. These studies support a role of DNA and protein-based vaccines for development of an efficacious HIV/AIDS vaccine.

  3. Immunogenicity of DNA Vaccines Encoding Simian Immunodeficiency Virus Antigen Targeted to Dendritic Cells in Rhesus Macaques

    PubMed Central

    Nchinda, Godwin; Trumpfheller, Christine; Salazar, Andres M.; Töpfer, Katharina; Sauermann, Ulrike; Wagner, Ralf; Hannaman, Drew; Tenner-Racz, Klara; Racz, Paul; Stahl-Hennig, Christiane; Überla, Klaus

    2012-01-01

    Background Targeting antigens encoded by DNA vaccines to dendritic cells (DCs) in the presence of adjuvants enhances their immunogenicity and efficacy in mice. Methodology/Principal Findings To explore the immunogenicity of this approach in non-human primates, we generated a single chain antibody to the antigen uptake receptor DEC-205 expressed on rhesus macaque DCs. DNA vaccines encoding this single chain antibody fused to the SIV capsid protein were delivered to six monkeys each by either intramuscular electroporation or conventional intramuscular injection co-injected or not with poly ICLC, a stabilized poly I: C analogue, as adjuvant. Antibodies to capsid were induced by the DC-targeting and non-targeting control DNA delivered by electroporation while conventional DNA immunization at a 10-fold higher dose of DNA failed to induce detectable humoral immune responses. Substantial cellular immune responses were also observed after DNA electroporation of both DNAs, but stronger responses were induced by the non-targeting vaccine. Conventional immunization with the DC-targeting DNA at a 10-fold higher dose did not give rise to substantial cellular immune responses, neither when co-injected with poly ICLC. Conclusions/Significance The study confirms the potent immunogenicity of DNA vaccines delivered by electroporation. Targeting the DNA via a single chain antibody to DEC-205 expressed by DCs, however, does not improve the immunogenicity of the antigens in non-human primates. PMID:22720025

  4. Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus

    SciTech Connect

    Kaur, Amitinder . E-mail: amitinder_kaur@hms.harvard.edu; Sanford, Hannah B.; Garry, Deirdre; Lang, Sabine; Klumpp, Sherry A.; Watanabe, Daisuke; Bronson, Roderick T.; Lifson, Jeffrey D.; Rosati, Margherita; Pavlakis, George N.; Felber, Barbara K.; Knipe, David M.; Desrosiers, Ronald C.

    2007-01-20

    The immunogenicity and protective capacity of replication-defective herpes simplex virus (HSV) vector-based vaccines were examined in rhesus macaques. Three macaques were inoculated with recombinant HSV vectors expressing Gag, Env, and a Tat-Rev-Nef fusion protein of simian immunodeficiency virus (SIV). Three other macaques were primed with recombinant DNA vectors expressing Gag, Env, and a Pol-Tat-Nef-Vif fusion protein prior to boosting with the HSV vectors. Robust anti-Gag and anti-Env cellular responses were detected in all six macaques. Following intravenous challenge with wild-type, cloned SIV239, peak and 12-week plasma viremia levels were significantly lower in vaccinated compared to control macaques. Plasma SIV RNA in vaccinated macaques was inversely correlated with anti-Rev ELISPOT responses on the day of challenge (P value < 0.05), anti-Tat ELISPOT responses at 2 weeks post challenge (P value < 0.05) and peak neutralizing antibody titers pre-challenge (P value 0.06). These findings support continued study of recombinant herpesviruses as a vaccine approach for AIDS.

  5. Adolescents and human immunodeficiency virus infection.

    PubMed

    Anderson, J R

    1992-12-01

    As of March 31, 1992, individuals 13 to 19 years of age had been diagnosed with acquired immunodeficiency syndrome; over one third were diagnosed in the past 2 years alone. Because of the long incubation period from initial infection to acquired immunodeficiency syndrome diagnosis, the majority of young adults with acquired immunodeficiency syndrome were probably initially infected as adolescents. In 1991, 34% of adolescents with acquired immunodeficiency syndrome were female, and their predominant mode of transmission was heterosexual contact. Human immunodeficiency virus seroprevalence studies of adolescents show a male-to-female ratio approaching 1:1, with many human immunodeficiency virus-infected adolescent women identifying none of the standard risk. Factors such as sexual and drug experimentation, risk taking, and sense of invulnerability so characteristic of adolescence put adolescents at special risk for human immunodeficiency virus. There is no published information on if or how clinical manifestations of human immunodeficiency virus disease in adolescents might differ from those seen in adults. Medical care should be broad-based and should include access to clinical trials for new drug treatments. General knowledge levels about acquired immunodeficiency syndrome are high among US adolescents, but behavioral changes have lagged behind. All adolescents should be targeted for intensive education about human immunodeficiency virus along with interventions designed to enhance their general coping, communication, and decision-making skills.

  6. Antiviral Drugs for Viruses Other Than Human Immunodeficiency Virus

    PubMed Central

    Razonable, Raymund R.

    2011-01-01

    Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M2 protein or the enzyme neuraminidase. Combination therapy with Interferon-α and ribavirin remains the backbone treatment for chronic hepatitis C; the addition of serine protease inhibitors improves the treatment outcome of patients infected with hepatitis C virus genotype 1. Chronic hepatitis B can be treated with interferon or a combination of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for the treatment of chronic hepatitis B possess anti–human immunodeficiency virus properties, and they inhibit replication of hepatitis B virus by serving as competitive substrates for its DNA polymerase. Some antiviral drugs possess multiple potential clinical applications, such as ribavirin for the treatment of chronic hepatitis C and respiratory syncytial virus and cidofovir for the treatment of cytomegalovirus and other DNA viruses. Drug resistance is an emerging threat to the clinical utility of antiviral drugs. The major mechanisms for drug resistance are mutations in the viral DNA polymerase gene or in genes that encode for the viral kinases required for the activation of certain drugs such as acyclovir and ganciclovir. Widespread antiviral resistance has limited the clinical utility of M2 inhibitors for the prevention and treatment of influenza infections. This article provides an overview of clinically available antiviral drugs for the primary care physician, with a special focus on pharmacology, clinical uses, and adverse effects. PMID

  7. Molecular Evidence for Mother-to-Child Transmission of Multiple Variants by Analysis of RNA and DNA Sequences of Human Immunodeficiency Virus Type 1

    PubMed Central

    Pasquier, C.; Cayrou, C.; Blancher, A.; Tourne-Petheil, C.; Berrebi, A.; Tricoire, J.; Puel, J.; Izopet, J.

    1998-01-01

    We have examined the viral selection that may occur during transmission by studying the env gene sequences from four cases of mother-to-child transmission of human immunodeficiency virus type 1. The V3 region sequences were directly amplified from both plasma viral RNA and peripheral blood mononuclear cells containing proviral DNA from mothers at delivery and at the time of diagnosis for children. Transmission occurred perinatally in three cases. The similarity of the viral sequences in each infant sample contrasted with the heterogeneous viral populations in the mothers. Phylogenetic analysis indicated the transmission of one or a few closely related maternal minor virus variants. In contrast, the child virus population in the fourth case was as heterogeneous as that of his mother, and phylogenetic analysis strongly suggested the transmission of multiple maternal variants. This case of multiple transmission was confirmed by analyzing sequences obtained at three times after delivery. Strains with sequences corresponding to the syncytium-inducing phenotype were also transmitted in this fourth case, and this was associated with the rapid development of disease in the child. There was no evidence for transmission of particular viral variants from mother to infant. We have thus described a particular case of vertical human immunodeficiency virus type 1 transmission with the transmission of multiple maternal variants to the infant and a rapid, fatal outcome in the child. PMID:9765386

  8. Adjuvanting a DNA vaccine with a TLR9 ligand plus Flt3 ligand results in enhanced cellular immunity against the simian immunodeficiency virus.

    PubMed

    Kwissa, Marcin; Amara, Rama R; Robinson, Harriet L; Moss, Bernard; Alkan, Sefik; Jabbar, Abdul; Villinger, Francois; Pulendran, Bali

    2007-10-29

    DNA vaccines offer promising strategies for immunization against infections. However, their clinical use requires improvements in immunogenicity. We explored the efficacy of Toll-like receptor (TLR) ligands (TLR-Ls) on augmenting the immunogenicity of a DNA prime-modified vaccinia virus Ankara (MVA) boost vaccine against SIV. Rhesus macaques were injected with Fms-like tyrosine kinase 3 (Flt3)-ligand (FL) to expand dendritic cells (DCs) and were primed with a DNA vaccine encoding immunodeficiency virus antigens mixed with ligands for TLR9 or TLR7/8. Subsequently, the animals were boosted with DNA and twice with recombinant MVA expressing the same antigens. TLR9-L (CpG DNA) mediated activation of DCs in vivo and enhanced the magnitude of antigen-specific CD8(+) interferon (IFN) gamma(+) T cells and polyfunctional CD8(+) T cells producing IFN-gamma, tumor necrosis factor alpha, and interleukin 2. Although this trial was designed primarily as an immunogenicity study, we challenged the animals with pathogenic SIVmac(251) and observed a reduction in peak viremia and cumulative viral loads in the TLR9-L plus FL-adjuvanted group relative to the unvaccinated group; however, the study design precluded comparisons between the adjuvanted groups and the group vaccinated with DNA/MVA alone. Viral loads were inversely correlated with the magnitude and quality of the immune response. Thus, the immunogenicity of DNA vaccines can be augmented with TLR9-L plus FL. PMID:17954572

  9. Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0 A resolution shows bent DNA.

    PubMed Central

    Jacobo-Molina, A; Ding, J; Nanni, R G; Clark, A D; Lu, X; Tantillo, C; Williams, R L; Kamer, G; Ferris, A L; Clark, P

    1993-01-01

    The crystal structure of a ternary complex of human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) heterodimer (p66/p51), a 19-base/18-base double-stranded DNA template-primer, and a monoclonal antibody Fab fragment has been determined at 3.0 A resolution. The four individual subdomains of RT that make up the polymerase domains of p66 and p51 are named fingers, palm, thumb, and connection [Kohlstaedt, L. A., Wang, J., Friedman, J. M., Rice, P. A. & Steitz, T. A. (1992) Science 256, 1783-1790]. The overall folding of the subdomains is similar in p66 and p51 but the spatial arrangements of the subdomains are dramatically different. The template-primer has A-form and B-form regions separated by a significant bend (40-45 degrees). The most numerous nucleic acid interactions with protein occur primarily along the sugar-phosphate backbone of the DNA and involve amino acid residues of the palm, thumb, and fingers of p66. Highly conserved regions are located in the p66 palm near the polymerase active site. These structural elements, together with two alpha-helices of the thumb of p66, act as a clamp to position the template-primer relative to the polymerase active site. The 3'-hydroxyl of the primer terminus is close to the catalytically essential Asp-110, Asp-185, and Asp-186 residues at the active site and is in a position for nucleophilic attack on the alpha-phosphate of an incoming nucleoside triphosphate. The structure of the HIV-1 RT/DNA/Fab complex should aid our understanding of general mechanisms of nucleic acid polymerization. AIDS therapies may be enhanced by a fuller understanding of drug inhibition and resistance emerging from these studies. Images Fig. 1 Fig. 2 Fig. 3 PMID:7687065

  10. Human immunodeficiency virus type 1 reverse transcriptase tG:T mispair formation on RNA and DNA templates with mismatched primers: a kinetic and thermodynamic study.

    PubMed Central

    Sala, M; Wain-Hobson, S; Schaeffer, F

    1995-01-01

    The relationship between human immunodeficiency virus (HIV) type 1 reverse transcriptase tG:T mispair formation and base pair stability was investigated using DNA and RNA templates with 15 bp matched or mismatched DNA primers. tG:T mispair formation during primer elongation was undetectable on tDNA-DNA duplexes but occurred with a frequency of 10(-4) on matched tRNA-DNA duplexes. The frequency increased to 7.0 x 10(-4) and 1.3 x 10(-3) on tRNA-DNA duplexes with tG:T mismatches located 6 and 9 bp beyond the polymerization site. From Km values at 37 degrees C, the free energy change upon dissociation (delta G degrees 37) of the tG:T mispair increased from matched to mismatched tRNA-DNA duplexes by 0.36-1.21 kcal/mol. delta G degrees 37 for a correct tG:C pair decreased by 0.06-1.00 kcal/mol. In comparison with DNA-DNA duplexes, thermal melting measurements on RNA-DNA duplexes demonstrated smaller enthalpy (delta delta H degrees = -17.7 to -28.1 kcal/mol) and entropy (delta delta S degrees = -59.3 to -83.4 cal/mol/K) components. A strong entropy-enthalpy compensation resulted in small free energy differences (delta delta G degrees 37 = 0.8 to -2.2 kcal/mol). Thus, although DNA-DNA and RNA-DNA duplexes are of comparable stability in solution, the RNA-DNA duplex presents more facile base pair opening and higher conformational flexibility. The release of helical strain at constant helix stability in RNA-DNA duplexes may facilitate base mispairing during reverse transcription, particularly in the context of lentiviral G-->A hypermutation. PMID:7556105

  11. Evaluation of the functional involvement of human immunodeficiency virus type 1 integrase in nuclear import of viral cDNA during acute infection.

    PubMed

    Ikeda, Tamako; Nishitsuji, Hironori; Zhou, Xin; Nara, Nobuo; Ohashi, Takashi; Kannagi, Mari; Masuda, Takao

    2004-11-01

    Nuclear import of viral cDNA is a critical step for establishing the proviral state of human immunodeficiency virus type 1 (HIV-1). The contribution of HIV-1 integrase (IN) to the nuclear import of viral cDNA is controversial, partly due to a lack of identification of its bona fide nuclear localization signal. In this study, to address this putative function of HIV-1 IN, the effects of mutations at key residues for viral cDNA recognition (PYNP at positions 142 to 145, K156, K159, and K160) were evaluated in the context of viral replication. During acute infection, some mutations (N144Q, PYNP>KL, and KKK>AAA) severely reduced viral gene expression to less than 1% the wild-type (WT) level. None of the mutations affected the synthesis of viral cDNA. Meanwhile, the levels of integrated viral cDNA produced by N144Q, PYNP>KL, and KKK>AAA mutants were severely reduced to less than 1% the WT level. Quantitative PCR analysis of viral cDNA in nuclei and fluorescence in situ hybridization analysis showed that these mutations significantly reduced the level of viral cDNA accumulation in nuclei. Further analysis revealed that IN proteins carrying the N144Q, PYNP>KL, and KKK>AAA mutations showed severely reduced binding to viral cDNA but kept their karyophilic properties. Taken together, these results indicate that mutations that reduced the binding of IN to viral cDNA resulted in severe impairment of virus infectivity, most likely by affecting the nuclear import of viral cDNA that proceeds integration. These results suggest that HIV-1 IN may be one of the critical constituents for the efficient nuclear import of viral cDNA.

  12. Chemical trapping of ternary complexes of human immunodeficiency virus type 1 integrase, divalent metal, and DNA substrates containing an abasic site. Implications for the role of lysine 136 in DNA binding.

    PubMed

    Mazumder, A; Neamati, N; Pilon, A A; Sunder, S; Pommier, Y

    1996-11-01

    We report a novel assay for monitoring the DNA binding of human immunodeficiency virus type 1 (HIV-1) integrase and the effect of cofactors and inhibitors. The assay uses depurinated oligonucleotides that can form a Schiff base between the aldehydic abasic site and a nearby enzyme lysine epsilon-amino group which can subsequently be trapped by reduction with sodium borohydride. Chemically depurinated duplex substrates representing the U5 end of the HIV-1 DNA were initially used. We next substituted an enzymatically generated abasic site for each of 10 nucleotides normally present in a 21-mer duplex oligonucleotide representing the U5 end of the HIV-1 DNA. Using HIV-1, HIV-2, or simian immunodeficiency virus integrases, the amount of covalent enzyme-DNA complex trapped decreased as the abasic site was moved away from the conserved CA dinucleotide. The enzyme-DNA complexes formed in the presence of manganese were not reversed by subsequent addition of EDTA, indicating that the divalent metal required for integrase catalysis is tightly bound in a ternary enzyme-metal-DNA complex. Both the N- and C-terminal domains of integrase contributed to efficient DNA binding, and mutation of Lys-136 significantly reduced Schiff base formation, implicating this residue in viral DNA binding.

  13. Pediatric human immunodeficiency virus infection.

    PubMed Central

    Domachowske, J B

    1996-01-01

    In the past decade, an increase in pediatric human immunodeficiency virus (HIV) infection has had a substantial impact on childhood morbidity and mortality worldwide. The vertical transmission of HIV from mother to infant accounts for the vast majority of these cases. Identification of HIV-infected pregnant women needs to be impoved so that appropriate therapy can be initiated for both mothers and infants. While recent data demonstrate a dramatic decrease in HIV transmission from a subset of women treated with zidovudine during pregnancy, further efforts at reducing transmission are desperately needed. This review focuses on vertically transmitted HIV infection in children, its epidemiology, diagnostic criteria, natural history, and clinical manifestations including infectious and noninfectious complications. An overview of the complex medical management of these children ensues, including the use of antiretroviral therapy. Opportunistic infection prophylaxis is reviewed, along with the important role of other supportive therapies. PMID:8894346

  14. Detection of BK virus DNA in nasopharyngeal aspirates from children with respiratory infections but not in saliva from immunodeficient and immunocompetent adult patients.

    PubMed Central

    Sundsfjord, A; Spein, A R; Lucht, E; Flaegstad, T; Seternes, O M; Traavik, T

    1994-01-01

    Our understanding of important stages in the pathogenesis of the human polyomavirus BK virus (BKV) and JC virus (JCV) infections is limited. In this context, nasopharyngeal aspirates from 201 children with respiratory diseases and saliva from 60 human immunodeficiency virus type 1-infected adults and 10 healthy adult controls were collected and analyzed for the presence of BKV and JCV DNA by PCR. Neither BKV nor JCV DNA was detected in the saliva specimens. We demonstrated BKV DNA, but no infectious BKV, in 2 of 201 nasopharyngeal aspirates. Each sample contained one unique rearranged noncoding control region variant of BKV. The results indicate that (i) BKV and JCV are not regularly associated with respiratory infections in children requiring hospitalization, (ii) nasopharyngeal cells are not an important site for primary replication of human polyomavirus BKV and JCV, and (iii) the salivary glands and oropharyngeal cells seem not to be involved in BKV and JCV persistence. We propose that for the polyomaviruses BKV and JCV the alimentary tract should be considered as a portal of entrance to the human organism. Images PMID:8051277

  15. Uracil DNA Glycosylase Is Dispensable for Human Immunodeficiency Virus Type 1 Replication and Does Not Contribute to the Antiviral Effects of the Cytidine Deaminase Apobec3G

    PubMed Central

    Kaiser, Shari M.; Emerman, Michael

    2006-01-01

    It is well established that many host factors are involved in the replication of human immunodeficiency virus (HIV) type 1. One host protein, uracil DNA glycosylase 2 (UNG2), binds to multiple viral proteins and is packaged into HIV type 1 virions. UNG initiates the removal of uracils from DNA, and this has been proposed to be important both for reverse transcription and as a mediator to the antiviral effect of virion-incorporated Apobec3G, a cytidine deaminase that generates numerous uracils in the viral DNA during virus replication. We used a natural human UNG−/− cell line as well as cells that express a potent catalytic active-site inhibitor of UNG to assess the effects of removing UNG activity on HIV infectivity. In both cases, we find UNG2 activity and protein to be completely dispensable for virus replication. Moreover, we find that virion-associated UNG2 does not affect the loss of infectivity caused by Apobec3G. PMID:16378989

  16. Susceptibility Testing by Polymerase Chain Reaction DNA Quantitation: A Method to Measure Drug Resistance of Human Immunodeficiency Virus Type 1 Isolates

    NASA Astrophysics Data System (ADS)

    Eron, Joseph J.; Gorczyca, Paul; Kaplan, Joan C.; D'Aquila, Richard T.

    1992-04-01

    Polymerase chain reaction (PCR) DNA quantitation (PDQ) susceptibility testing rapidly and directly measures nucleoside sensitivity of human immunodeficiency virus type 1 (HIV-1) isolates. PCR is used to quantitate the amount of HIV-1 DNA synthesized after in vitro infection of peripheral blood mononuclear cells. The relative amounts of HIV-1 DNA in cell lysates from cultures maintained at different drug concentrations reflect drug inhibition of virus replication. The results of PDQ susceptibility testing of 2- or 3-day cultures are supported by assays measuring HIV-1 p24 antigen production in supernatants of 7- or 10-day cultures. DNA sequence analyses to identify mutations in the reverse transcriptase gene that cause resistance to 3'-azido-3'-deoxythymidine also support the PDQ results. With the PDQ method, both infectivity titration and susceptibility testing can be performed on supernatants from primary cultures of peripheral blood mononuclear cells. PDQ susceptibility testing should facilitate epidemiologic studies of the clinical significance of drug-resistant HIV-1 isolates.

  17. Susceptibility testing by polymerase chain reaction DNA quantitation: a method to measure drug resistance of human immunodeficiency virus type 1 isolates.

    PubMed

    Eron, J J; Gorczyca, P; Kaplan, J C; D'Aquila, R T

    1992-04-15

    Polymerase chain reaction (PCR) DNA quantitation (PDQ) susceptibility testing rapidly and directly measures nucleoside sensitivity of human immunodeficiency virus type 1 (HIV-1) isolates. PCR is used to quantitate the amount of HIV-1 DNA synthesized after in vitro infection of peripheral blood mononuclear cells. The relative amounts of HIV-1 DNA in cell lysates from cultures maintained at different drug concentrations reflect drug inhibition of virus replication. The results of PDQ susceptibility testing of 2- or 3-day cultures are supported by assays measuring HIV-1 p24 antigen production in supernatants of 7- or 10-day cultures. DNA sequence analyses to identify mutations in the reverse transcriptase gene that cause resistance to 3'-azido-3'-deoxythymidine also support the PDQ results. With the PDQ method, both infectivity titration and susceptibility testing can be performed on supernatants from primary cultures of peripheral blood mononuclear cells. PDQ susceptibility testing should facilitate epidemiologic studies of the clinical significance of drug-resistant HIV-1 isolates.

  18. Screening for Human Immunodeficiency Virus (HIV)

    MedlinePlus

    ... Task Force learned about the potential benefits and harms of this screening: (1) Everyone aged 15 to ... the disease to other people. Potential Benefits and Harms of Screening for Human Immunodeficiency Virus (HIV) The ...

  19. Inhibition of human immunodeficiency virus type 1 transcription and replication by DNA sequence-selective plant lignans.

    PubMed

    Gnabre, J N; Brady, J N; Clanton, D J; Ito, Y; Dittmer, J; Bates, R B; Huang, R C

    1995-11-21

    A plant lignan, 3'-O-methyl nordihydroguaiaretic acid (3'-O-methyl NDGA, denoted Malachi 4:5-6 or Mal.4; molecular weigth 316), was isolated from Larrea tridentata and found to be able to inhibit human immunodeficiency virus (HIV) Tat-regulated transactivation in vivo, induce protection of lymphoblastoid CEM-SS cells from HIV (strain IIIB) killing, and suppress the replication of five HIV-1 strains (WM, MN, VS, JR-CSF, and IIIB) in mitogen-stimulated peripheral blood mononuclear cells, all in a dose-dependent manner. Mal.4 inhibits both basal transcription and Tat-regulated transactivation in vitro. The target of Mal.4 has been localized to nucleotides -87 to -40 of the HIV long terminal repeat. Mal.4 directly and specifically interferes with the binding of Sp1 to Sp1 sites in the HIV long terminal repeat. By inhibiting proviral expression, Mal.4 may be able to interrupt the life cycles of both wild-type and reverse transcriptase or protease mutant viruses in HIV-infected patients. PMID:7479972

  20. Rapid, point-of-care extraction of human immunodeficiency virus type 1 proviral DNA from whole blood for detection by real-time PCR.

    PubMed

    Jangam, Sujit R; Yamada, Douglas H; McFall, Sally M; Kelso, David M

    2009-08-01

    PCR detection of human immunodeficiency virus type 1 (HIV-1) proviral DNA is the method recommended for use for the diagnosis of HIV-1 infection in infants in limited-resource settings. Currently, testing must be performed in central laboratories, which are usually located some distance from health care facilities. While the collection and transportation of samples, such as dried blood spots, has improved test accessibility, the results are often not returned for several weeks. To enable PCR to be performed at the point of care while the mothers wait, we have developed a vertical filtration method that uses a separation membrane and an absorbent pad to extract cellular DNA from whole blood in less than 2 min. Cells are trapped in the separation membrane as the specimen is collected, and then a lysis buffer is added. The membrane retains the DNA, while the buffer washes away PCR inhibitors, which get wicked into the absorbent blotter pad. The membrane containing the entrapped DNA is then added to the PCR mixture without further purification. The method demonstrates a high degree of reproducibility and analytical sensitivity and allows the quantification of as few as 20 copies of HIV-1 proviral DNA from 100 microl of blood. In a blinded study with 182 longitudinal samples from infants (ages, 0 to 72 weeks) obtained from the Women and Infants Transmission Study, our assay demonstrated a sensitivity of 99% and a specificity of 100%. PMID:19644129

  1. Inhibitors of human immunodeficiency virus integrase.

    PubMed Central

    Fesen, M R; Kohn, K W; Leteurtre, F; Pommier, Y

    1993-01-01

    In an effort to further extend the number of targets for development of antiretroviral agents, we have used an in vitro integrase assay to investigate a variety of chemicals, including topoisomerase inhibitors, antimalarial agents, DNA binders, naphthoquinones, the flavone quercetin, and caffeic acid phenethyl ester as potential human immunodeficiency virus type 1 integrase inhibitors. Our results show that although several topoisomerase inhibitors--including doxorubicin, mitoxantrone, ellipticines, and quercetin--are potent integrase inhibitors, other topoisomerase inhibitors--such as amsacrine, etoposide, teniposide, and camptothecin--are inactive. Other intercalators, such as chloroquine and the bifunctional intercalator ditercalinium, are also active. However, DNA binding does not correlate closely with integrase inhibition. The intercalator 9-aminoacridine and the polyamine DNA minor-groove binders spermine, spermidine, and distamycin have no effect, whereas the non-DNA binders primaquine, 5,8-dihydroxy-1,4-naphthoquinone, and caffeic acid phenethyl ester inhibit the integrase. Caffeic acid phenethyl ester was the only compound that inhibited the integration step to a substantially greater degree than the initial cleavage step of the enzyme. A model of 5,8-dihydroxy-1,4-naphthoquinone interaction with the zinc finger region of the retroviral integrase protein is proposed. Images Fig. 2 PMID:8460151

  2. Recruitment of Antigen-Presenting Cells to the Site of Inoculation and Augmentation of Human Immunodeficiency Virus Type 1 DNA Vaccine Immunogenicity by In Vivo Electroporation▿

    PubMed Central

    Liu, Jinyan; Kjeken, Rune; Mathiesen, Iacob; Barouch, Dan H.

    2008-01-01

    In vivo electroporation (EP) has been shown to augment the immunogenicity of plasmid DNA vaccines, but its mechanism of action has not been fully characterized. In this study, we show that in vivo EP augmented cellular and humoral immune responses to a human immunodeficiency virus type 1 Env DNA vaccine in mice and allowed a 10-fold reduction in vaccine dose. This enhancement was durable for over 6 months, and re-exposure to antigen resulted in anamnestic effector and central memory CD8+ T-lymphocyte responses. Interestingly, in vivo EP also recruited large mixed cellular inflammatory infiltrates to the site of inoculation. These infiltrates contained 45-fold-increased numbers of macrophages and 77-fold-increased numbers of dendritic cells as well as 2- to 6-fold-increased numbers of B and T lymphocytes compared to infiltrates following DNA vaccination alone. These data suggest that recruiting inflammatory cells, including antigen-presenting cells (APCs), to the site of antigen production substantially improves the immunogenicity of DNA vaccines. Combining in vivo EP with plasmid chemokine adjuvants that similarly recruited APCs to the injection site, however, did not result in synergy. PMID:18353952

  3. Simple, Sensitive, and Specific Detection of Human Immunodeficiency Virus Type 1 Subtype B DNA in Dried Blood Samples for Diagnosis in Infants in the Field

    PubMed Central

    Beck, Ingrid A.; Drennan, Kathryn D.; Melvin, Ann J.; Mohan, Kathey M.; Herz, Arnd M.; Alarcón, Jorge; Piscoya, Julia; Velázquez, Carlos; Frenkel, Lisa M.

    2001-01-01

    The detection of virus is used to diagnose human immunodeficiency virus type 1 (HIV-1) infection in infants due to the persistence of maternal antibodies for a year or more. An HIV-1 DNA PCR assay with simple specimen collection and processing was developed and evaluated. Whole blood was collected on filter paper that lysed cells and bound the DNA, eliminating specimen centrifugation and extraction procedures. The DNA remained bound to the filter paper during PCR amplification. Assays of copy number standards showed reproducible detection of 5 to 10 copies of HIV-1 in 5 μl of whole blood. The sensitivity of the assay did not decrease after storage of the standards on filter paper for 3 months at room temperature or after incubation at 37 or 45°C for 20 h. The primers used for nested PCR of the HIV-1 pol gene amplified templates from a reference panel of multiple HIV-1 subtypes but did not amplify a subtype A or a subtype C virus from children living in Seattle. The assay had a sensitivity of 98.4% and a specificity of 98.3% for testing of 122 specimens from 35 HIV-1-infected and 16 uninfected children and 43 seronegative adults living in Washington. The assay had a sensitivity of 99% and a specificity of 100% for testing of 102 HIV-1-positive (as determined by enzyme immunoassay) Peruvian women and 6 seropositive and 34 seronegative infants. This assay, with adsorption of whole blood to filter paper and no specimen processing, provides a practical, economical, sensitive, and specific method for the diagnosis of HIV-1 subtype B infection in infants. PMID:11136743

  4. Pharmacovirological impact of an integrase inhibitor on human immunodeficiency virus type 1 cDNA species in vivo.

    PubMed

    Goffinet, Christine; Allespach, Ina; Oberbremer, Lena; Golden, Pamela L; Foster, Scott A; Johns, Brian A; Weatherhead, Jason G; Novick, Steven J; Chiswell, Karen E; Garvey, Edward P; Keppler, Oliver T

    2009-08-01

    Clinical trials of the first approved integrase inhibitor (INI), raltegravir, have demonstrated a drop in the human immunodeficiency virus type 1 (HIV-1) RNA loads of infected patients that was unexpectedly more rapid than that with a potent reverse transcriptase inhibitor, and apparently dose independent. These clinical outcomes are not understood. In tissue culture, although their inhibition of integration is well documented, the effects of INIs on levels of unintegrated HIV-1 cDNAs have been variable. Furthermore, there has been no report to date on an INI's effect on these episomal species in vivo. Here, we show that prophylactic treatment of transgenic rats with the strand transfer INI GSK501015 reduced levels of viral integrants in the spleen by up to 99.7%. Episomal two-long-terminal-repeat (LTR) circles accumulated up to sevenfold in this secondary lymphoid organ, and this inversely correlated with the impact on the proviral burden. Contrasting raltegravir's dose-ranging study with HIV patients, titration of GSK501015 in HIV-infected animals demonstrated dependence of the INI's antiviral effect on its serum concentration. Furthermore, the in vivo 50% effective concentration calculated from these data best matched GSK501015's in vitro potency when serum protein binding was accounted for. Collectively, this study demonstrates a titratable, antipodal impact of an INI on integrated and episomal HIV-1 cDNAs in vivo. Based on these findings and known biological characteristics of viral episomes, we discuss how integrase inhibition may result in additional indirect antiviral effects that contribute to more rapid HIV-1 decay in HIV/AIDS patients.

  5. Quantitation of human immunodeficiency virus type 1 DNA forms with the second template switch in peripheral blood cells predicts disease progression independently of plasma RNA load.

    PubMed

    Kostrikis, Leondios G; Touloumi, Giota; Karanicolas, Rose; Pantazis, Nikos; Anastassopoulou, Cleo; Karafoulidou, Anastasia; Goedert, James J; Hatzakis, Angelos

    2002-10-01

    There are several forms of human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood T cells and lymph nodes in untreated HIV-1-infected individuals and in patients whose plasma HIV-1 RNA levels are suppressed by long-term combination antiretroviral therapy. However, it remains to be established whether the concentration of HIV-1 DNA in cells predicts the clinical outcome of HIV-1 infection. In this report, we measured the concentration of HIV-1 DNA forms which has undergone the second template switch (STS DNA) and 2-long-terminal-repeat DNA circles in peripheral blood mononuclear cell (PBMC) samples. To do this, we used molecular-beacon-based real-time PCR assays and studied 130 patients with hemophilia in the Multicenter Hemophilia Cohort Study. We assessed the influence of baseline HIV-1 STS DNA levels on the progression of HIV-1 disease in the absence of combination antiretroviral therapy by Kaplan-Meier and Cox regression analysis. Among the patients who progressed to AIDS, the median levels (interquartile ranges) of STS HIV-1 DNA in PBMC were significantly higher than those of patients who remained AIDS free during the 16 years of follow-up (1,017 [235 to 6,059] and 286 [31 to 732] copies per 10(6) PBMC, respectively; P < 0.0001). Rates of progression to death and development of AIDS varied significantly (log rank P < 0.001) by quartile distribution of HIV-1 STS DNA levels. After adjustment for age at seroconversion, baseline CD4(+) T-cell counts, plasma viral load, and T-cell-receptor excision circles, the relative hazards (RH) of death and AIDS were significantly increased with higher HIV-1 STS DNA levels (adjusted RH, 1.84 [95% confidence interval (CI), 1.30 to 2.59] and 2.62 [95% CI, 1.75 to 3.93] per 10-fold increase per 10(6) PBMC, respectively). HIV-1 STS DNA levels in each individual remained steady in longitudinal PBMC samples during 16 years of follow-up. Our findings show that the concentration of HIV-1 STS DNA in PBMC complements the HIV

  6. Antiviral therapy for human immunodeficiency virus infections.

    PubMed Central

    De Clercq, E

    1995-01-01

    Depending on the stage of their intervention with the viral replicative cycle, human immunodeficiency virus inhibitors could be divided into the following groups: (i) adsorption inhibitors (i.e., CD4 constructs, polysulfates, polysulfonates, polycarboxylates, and polyoxometalates), (ii) fusion inhibitors (i.e., plant lectins, succinylated or aconitylated albumins, and betulinic acid derivatives), (iii) uncoating inhibitors (i.e., bicyclams), (iv) reverse transcription inhibitors acting either competitively with the substrate binding site (i.e., dideoxynucleoside analogs and acyclic nucleoside phosphonates) or allosterically with a nonsubstrate binding site (i.e., non-nucleoside reverse transcriptase inhibitors), (v) integration inhibitors, (vi) DNA replication inhibitors, (vii) transcription inhibitors (i.e., antisense oligodeoxynucleotides and Tat antagonists), (viii) translation inhibitors (i.e., antisense oligodeoxynucleotides and ribozymes), (ix) maturation inhibitors (i.e., protease inhibitors, myristoylation inhibitors, and glycosylation inhibitors), and finally, (x) budding (assembly/release) inhibitors. Current knowledge, including the therapeutic potential, of these various inhibitors is discussed. In view of their potential clinical the utility, the problem of virus-drug resistance and possible strategies to circumvent this problem are also addressed. PMID:7542558

  7. Acquired immunodeficiency syndrome and human immunodeficiency virus infection in Nevada.

    PubMed

    Jarvis, J Q; Semiatin, S L

    1991-01-01

    We summarize information from three sets of epidemiologic data: the Nevada AIDS [acquired immunodeficiency syndrome] Surveillance System, which contains information about every case identified within the state boundaries through September 1989; the human immunodeficiency virus (HIV) seroprevalence reporting systems, which currently include data on all HIV-positive reports submitted statewide to public health authorities; and surveys on the knowledge, attitudes, and behaviors of Nevadans concerning HIV-related disease. The Nevada State AIDS Task Force outlined major policy recommendations, nearly half of which concerned testing; only 2 dealt with preventing HIV transmission. Greater efforts should go into education, particularly directed toward groups at greatest risk of exposure to HIV, and to improve community-based care of infected persons.

  8. Fatal encephalitis due to BK virus in a patient with common variable immunodeficiency: a case report.

    PubMed

    Bakri, Faris G; Bahou, Yacoub G; Al-Sammarrai, Firas A; Hadidy, Azmy; Gharaibeh, Almutez; Zaid, Ghida K; Mahafzah, Azmi; Samara, Osama A; Ababneh, Nidaa A; Zak, Imad

    2013-08-01

    Encephalitis due to BK virus is a rare condition. Here, we describe a young male patient with common variable immunodeficiency who developed fatal encephalitis due to BK virus. The patient presented initially with ocular symptoms that were followed by behavioral changes and spastic quadriparesis. Diagnosis was made by the compatible clinical findings and detection of viral DNA by polymerase chain reaction in the cerebrospinal fluid. To the best of our knowledge, this is the first report of BK virus encephalitis in a patient with common variable immunodeficiency. We suggest that BK virus should be suspected in cases of encephalitis; particularly in patients with immunodeficiency.

  9. Women at Risk for Human Immunodeficiency Virus.

    ERIC Educational Resources Information Center

    Quadagno, David; And Others

    This article reports results from a survey among women at risk for contracting Human Immunodeficiency Virus (HIV) as well as transmitting it in a vertical (to offspring) and horizontal (sexual partner or intravenous [IV] drug usage) mode. Little is known about the extent of HIV knowledge, sexual behaviors, and IV drug usage for women at risk for…

  10. Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome in Older Adults.

    PubMed

    Scott, Jake; Goetz, Matthew Bidwell

    2016-08-01

    Improved survival with combination antiretroviral therapy has led to a dramatic increase in the number of human immunodeficiency virus (HIV)-infected individuals 50 years of age or older such that by 2020 more than 50% of HIV-infected persons in the United States will be above this age. Recent studies confirm that antiretroviral therapy should be offered to all HIV-infected patients regardless of age, symptoms, CD4+ cell count, or HIV viral load. However, when compared with HIV-uninfected populations, even with suppression of measurable HIV replication, older individuals are at greater risk for cardiovascular disease, malignancies, liver disease, and other comorbidities.

  11. Feline Immunodeficiency Virus in South America

    PubMed Central

    Teixeira, Bruno M.; Hagiwara, Mitika K.; Cruz, Juliano C. M.; Hosie, Margaret J.

    2012-01-01

    The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV) have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species). Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV) causes an immune system disease in domestic cats (Felis catus) involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs) in South America. PMID:22590677

  12. Quantification of Hepatitis C Virus (HCV) in Liver Specimens and Sera from Patients with Human Immunodeficiency Virus Coinfection by Using the Versant HCV RNA 3.0 (Branched DNA-Based) DNA Assay

    PubMed Central

    Tedeschi, Rosamaria; Pivetta, Eliana; Zanussi, Stefania; Bidoli, Ettore; Ros, Mirna; di Gennaro, Giampiero; Nasti, Guglielmo; De Paoli, Paolo

    2003-01-01

    The new generation assay Versant HCV RNA 3.0v (Bayer Diagnostics) was evaluated to quantify hepatitis C virus (HCV) RNA levels in liver biopsy specimens from patients with HCV and human immunodeficiency virus (HIV) coinfection. A total of 25 liver biopsies and sera collected at the time of liver biopsy were used. The efficiency of HCV RNA recovery from spiked samples was between 38.6 and 50.7%, and reproducible measurements of viral load were observed (the intra- and interrun coefficients of variation were 0.5 to 13% and 3.5 to 24.7%, respectively), with good specificity and sensitivity. Linearity was evaluated in the range of 96,154 to 769 IU/μg by using a serially diluted high-titer sample. Coinfected patients had high HCV RNA viral loads in serum and liver (498,471 IU/ml and 231,495 IU/μg, respectively), and both levels were correlated (r = 0.63; P < 0.01). The amount of hepatic HCV RNA was significantly higher among patients with genotype 1 than among patients with genotype 3 (P < 0.01). The virological end-of-treatment response in the serum was associated with a lower pretreatment intrahepatic HCV viral load (P = 0.03). The new version of b-DNA is a sensitive, specific, and reproducible method for quantitating HCV RNA in the liver. Given its positive analytical performance, the assay will be used to evaluate the HCV RNA levels in the serum and liver during follow-up of patients treated with an anti-HCV therapeutic regimen. PMID:12843041

  13. 78 FR 46969 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-02

    ... Development and Human Immunodeficiency Virus Cure Research; Reopening of Comment Period AGENCY: Food and Drug... Virus (HIV) Patient-Focused Drug Development and HIV Cure Research,'' published in the Federal Register of May 21, 2013 (78 FR 29755). In that notice, FDA requested public comment regarding...

  14. Flow cytometric detection of human immunodeficiency virus type 1 proviral DNA by the polymerase chain reaction incorporating digoxigenin- or fluorescein-labeled dUTP

    SciTech Connect

    Yang, Gang; Olson, J.C.; Pu, R.; Vyas, G.N.

    1995-10-01

    Serological assays are routinely used in the laboratory diagnosis of human immunodeficiency virus type-1 (HrV-1) infection, but the polymerase chain reaction (PCR) is ultimately the most sensitive and direct method for establishing definitive diagnosis. As an alternative to the conventional radioactive PCR procedure we have developed and evaluated a pair of rapid nonradioisotopic flow cytometric detection methods. Using heminested PCR we directly incorporated fluorescein-12-dUTP (fluo-dUTP) or digoxigenin-11-dUTP (dig-dUTP) into the PCR-amplicons. The labeled amplicons were hybridized with biotinylated antisense and sense probes, followed by capture of the hybrid DNA using streptavidin-coated beads which were finally analyzed in a flow cytometer by (1) direct detection of the fluorescence intensity of the amplicons incorporating fluo-dUTP and (2) immunodetection of the amplicons incorporating dig-dUTP by anti-digoxigenin IgG labeled with fluorescein isothiocyanate (FITC). Although both assays were functionally comparable with radiolabeled probe in reliably detecting as low as five copies of HIV-1 proviral DNA sequences, the immunodetection of dig-dUTP consistently yielded higher mean channel fluorescence and gave a stable signal over an extended period of 12-14 weeks. In testing a panel of 20 pedigreed PBMC specimens from blood donors with or without HIV-1 infection, the results of both flow cytometric assays were identical with those of the conventional radioactive procedure. Therefore, we conclude that the dig-dUTP incorporation in amplicons, hybridization with a pair of sense-antisense biotinylated probes and immunodetection of hybrids by flow cytometric analyses is the nonisotopic method of choice for PCR-diagnosis of HIV-1 infection. 21 refs., 2 figs., 4 tabs.

  15. Detection of human immunodeficiency virus in infected CEM cells using fluorescent DNA probes and a laser-based computerized image cytofluorometry system.

    PubMed

    Hart, L; Donovan, R M; Goldstein, E; Brady, F P

    1990-04-01

    Quantitative nonradioactive methods to measure the human immunodeficiency virus (HIV) in individually infected cells are needed for the direct assessment of HIV infection, for the evaluation of antiviral chemotherapy and for testing the efficacy of vaccines. As a first step in accomplishing this goal, we built an argon ion laser-based computerized image cytofluorometry (ALCIC) system and determined this instrument's ability to quantitatively measure HIV nucleotides in infected lymphocytes. ALCIC consisted of a 43-mW argon ion laser connected to a Zeiss Universal microscope via a fiberoptic cable, a charged coupled-device video camera, a video frame grabber and array processor and a Micro Vax II computer using computer programs written in FORTRAN. HIV RNA and DNA were detected in infected CEM lymphocytes in culture by in situ hybridization using acetylaminofluorene (AAF)-labeled HIV-DNA probes, a rabbit anti-AAF antibody and a fluorescein-labeled goat anti-rabbit antibody. ALCIC measurements showed that 61% of the CEM cells were infected and that quantitative differences were distinguishable within this group. The levels of fluorescein isothiocyanate (FITC) fluorescence were sixfold or more greater than that observed with the same system using a 100-W mercury lamp for illumination; the improved intensity of the laser-based system is due to greater excitation intensity of the laser and the matching of the excitation spectrum to the peak wavelength of FITC. ALCIC has potential clinical value for determining the effect of antiviral agents on HIV infection and for assessing the susceptibility of different cell types to infection. PMID:2112391

  16. Rapid detection of Pneumocystis carinii in bronchoalveolar lavage specimens from human immunodeficiency virus-infected patients: use of a simple DNA extraction procedure and nested PCR.

    PubMed

    Rabodonirina, M; Raffenot, D; Cotte, L; Boibieux, A; Mayençon, M; Bayle, G; Persat, F; Rabatel, F; Trepo, C; Peyramond, D; Piens, M A

    1997-11-01

    We report on the development of a rapid nested PCR protocol for the detection of Pneumocystis carinii DNA in bronchoalveolar lavage (BAL) specimens in which the protocol included the use of a commercially available DNA extraction kit (GeneReleaser). GeneReleaser enabled us to obtain amplification-ready DNA within 20 min without requiring the purification of the DNA. The nested PCR was performed with the primers pAZ102-E, pAZ102-H, and pAZ102-L2 (A. E. Wakefield, F. J. Pixley, S. Banerji, K. Sinclair, R. F. Miller, E. R. Moxon, and J. M. Hopkin, Lancet 336:451-453, 1990.). Results were obtained in about 4 h with the adoption of denaturation, annealing, and extension steps shortened to 20 seconds. The sensitivity of the nested PCR was tested with a P. carinii cyst suspension and was found to be less than one cyst (one to eight nuclei). The detection limit was the same with the use of GeneReleaser or proteinase K-phenol chloroform for DNA extraction. The nested PCR assay was prospectively compared with staining with Giemsa and methenamine silver stains for the detection of P. carinii in 127 BAL samples from 105 human immunodeficiency virus-infected patients investigated for acute respiratory illness. Twenty-five BAL specimens (20%) were positive by staining and the nested PCR and 25 (20%) were negative by staining and positive by the nested PCR. These 25 BAL specimens with conflicting results were obtained from 23 patients, 82% of whom were receiving prophylactic therapy against P. carinii pneumonia (PCP). Only two patients were diagnosed with possible PCP. The final diagnosis was not PCP for 20 patients who were considered to be colonized or to have a low level of infection. This colonization is not of clinical importance but is of epidemiological importance. Our rapid, simple, and sensitive amplification protocol may be performed in clinical laboratories for the routine diagnosis of PCP with BAL specimens.

  17. Human Immunodeficiency Virus Infection and Pregnancy

    PubMed Central

    1994-01-01

    The human immunodeficiency virus (HIV) epidemic is clearly one of the most serious health-care crises in the professional lives of contemporary physicians. It cannot be regarded as a curiosity to be dealt with by inner-city infectious-disease experts, but rather must be considered a problem for all health-care providers and a problem in which the obstetrician-gynecologist has a special role to play. PMID:18475370

  18. New estimation method for highly sensitive quantitation of human immunodeficiency virus type 1 DNA and its application.

    PubMed

    Nagai, Hiromi; Wada, Kaoru; Morishita, Takayuki; Utsumi, Makoto; Nishiyama, Yukihiro; Kaneda, Tsuguhiro

    2005-03-01

    A new estimation method for quantitation of HIV-1 DNA was established by introducing a pre-quantitation polymerase chain reaction (PCR) before conventional real-time PCR. Two alternative methods for estimating the copy number can be used: the first method utilizes the rate of beta2-microglobulin (beta2M) gene amplification during the pre-quantitation PCR, and the second utilizes a calibration curve of the crossing point of real-time PCR versus the standard HIV-1-plasmid concentration. These methods could be used to reproducibly and accurately detect a provirus density down to five copies/10(6) cells (for methods 1 and 2, inter-assay CV=17 and 16% and accuracy=81 and 92%, respectively). The levels of HIV-1 DNA could be measurable using as little as 100 microl of whole blood or buffy coat cells. Using a combination of a conventional and highly sensitive methods, we found that the amount of HIV-1 DNA ranged from 2 to 5960 copies/10(6) cells (median of 830 copies/10(6) cells) in CD4-positive T lymphocytes isolated from 30 patients responding well to highly active antiretroviral therapy (HAART). Thus, the highly sensitive method developed in this study allows estimation of the HIV-1 reservoirs in peripheral CD4-positive T lymphocytes of patients responding well to HAART. PMID:15664064

  19. 78 FR 29755 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-21

    ... (78 FR 21613), FDA published a document that announced the disease ] areas for meetings in fiscal... immunodeficiency virus (HIV) Patient-Focused Drug Development and HIV Cure Research. Patient-Focused Drug... Fee Act (PDUFA V). FDA is interested in obtaining patient input on the impact of HIV on daily...

  20. Early Pathogenesis of Transmucosal Feline Immunodeficiency Virus Infection

    PubMed Central

    Obert, Leslie A.; Hoover, Edward A.

    2002-01-01

    To identify the early target cells and tissues in transmucosal feline immunodeficiency virus (FIV) infection, cats were exposed to a clade C FIV isolate via the oral-nasal or vaginal mucosa and multiple tissues were examined by virus isolation coculture (VI), DNA PCR, catalyzed tyramide signal-amplified in situ hybridization (TSA-ISH), and immunohistochemistry between days 1 and 12 postinoculation (p.i.). FIV RNA was detected in tonsil and oral or vaginal mucosa as early as 1 day p.i. by TSA-ISH and in retropharyngeal, tracheobronchial, or external iliac lymph nodes and sometimes in spleen or blood mononuclear cells by day 2, indicating that regional and distant spread of virus-infected cells occurred rapidly after mucosal exposure. By day 8, viral RNA, DNA, and culturable virus were uniformly detected in regional and distant tissues, connoting systemic infection. TSA-ISH proved more sensitive than DNA PCR in detecting early FIV-infected cells. In mucosal tissues, the earliest demonstrable FIV-bearing cells were either within or subjacent to the mucosal epithelium or were in germinal centers of regional lymph nodes. The FIV+ cells were of either of two morphological types, large stellate or small round. Those FIV RNA+ cells which could be colabeled for a phenotype marker, were labeled for either dendritic-cell-associated protein p55 or T-lymphocyte receptor antigen CD3. These studies indicate that FIV crosses mucous membranes within hours after exposure and rapidly traffics via dendritic and T cells to systemic lymphoid tissues, a pathway similar to that thought to occur in the initial phase of infection by the human and simian immunodeficiency viruses. PMID:12021364

  1. Endemic mycosis complicating human immunodeficiency virus infection.

    PubMed Central

    Sarosi, G A; DAvies, S F

    1996-01-01

    Persons infected with the human immunodeficiency virus are prone to the development of many fungal diseases. Normal hosts with intact immunity usually recover from infection by these less-invasive fungi. In persons with compromised T-cell-mediated immunity, however, widespread dissemination from a pulmonary focus occurs. In this review, we discuss the epidemiology, clinical manifestations, diagnosis, and treatment of the three major North American mycoses, histoplasmosis, blastomycosis, and coccidioidomycosis. In most cases, amphotericin B is the initial drug of choice, followed by one of the azoles for lifelong maintenance therapy. PMID:8732733

  2. Lipid management in human immunodeficiency virus.

    PubMed

    Myerson, Merle

    2015-05-01

    The development and use of antiretroviral medications to treat patients infected with human immunodeficiency virus (HIV) has dramatically changed the course of this disease from one that was fatal to a chronic and more manageable condition. Recommendations and guidelines for the general population are presented in this review with suggestions as to how they may be applied to this patient population. Issues for which there is little or no information available are noted to highlight the many gaps in our knowledge regarding diagnosis and management of dyslipidemia for patients living with HIV.

  3. Depoliticize Human Immunodeficiency Virus Infection: A Commentary

    PubMed Central

    1994-01-01

    Public-health policy is inconsistent in its approach to the sexually transmitted disease human immunodeficiency virus (HIV). Nearly every health agency has politicized the reporting, finding, and contacting of HIV cases. There is also no consistency among the various state health departments and the various federal health agencies. Until we have a uniform health policy that treats HIV infection as every other reportable sexually transmitted disease, we will make little progress toward controlling its inevitable increase in both cases and costs. PMID:18475369

  4. Human Immunodeficiency Virus Vaccine Trials

    PubMed Central

    O’Connell, Robert J.; Kim, Jerome H.; Corey, Lawrence; Michael, Nelson L.

    2012-01-01

    More than 2 million AIDS-related deaths occurred globally in 2008, and more than 33 million people are living with HIV/AIDS. Despite promising advances in prevention, an estimated 2.7 million new HIV infections occurred in that year, so that for every two patients placed on combination antiretroviral treatment, five people became infected. The pandemic poses a formidable challenge to the development, progress, and stability of global society 30 years after it was recognized. Experimental preventive HIV-1 vaccines have been administered to more than 44,000 human volunteers in more than 187 separate trials since 1987. Only five candidate vaccine strategies have been advanced to efficacy testing. The recombinant glycoprotein (rgp)120 subunit vaccines, AIDSVAX B/B and AIDSVAX B/E, and the Merck Adenovirus serotype (Ad)5 viral-vector expressing HIV-1 Gag, Pol, and Nef failed to show a reduction in infection rate or lowering of postinfection viral set point. Most recently, a phase III trial that tested a heterologous prime-boost vaccine combination of ALVAC-HIV vCP1521 and bivalent rgp120 (AIDSVAX B/E) showed 31% efficacy in protection from infection among community-risk Thai participants. A fifth efficacy trial testing a DNA/recombinant(r) Ad5 prime-boost combination is currently under way. We review the clinical trials of HIV vaccines that have provided insight into human immunogenicity or efficacy in preventing HIV-1 infection. PMID:23209178

  5. Ocular syphilis in patients with Human Immunodeficiency Virus infection.

    PubMed

    Mitchell, John P; Huang, Lynn L; Rosberger, Daniel F

    2015-06-01

    As Acquired Immunodeficiency Disease (AIDS) turns thirty-years old, much progress has been made. 56,000 new cases of the Human Immunodeficiency Virus (HIV) infection are expected in Americans this year. At least half or more will be in African Americans. Reports of the association between syphilis and HIV infection are well documented. We present a case of bilateral optic neuritis and panuveitis as the initial presentation in a previously undiagnosed patient with human immunodeficiency virus (HIV) and syphilis. PMID:27269502

  6. Pathogenesis of human immunodeficiency virus infection.

    PubMed Central

    Levy, J A

    1993-01-01

    The lentivirus human immunodeficiency virus (HIV) causes AIDS by interacting with a large number of different cells in the body and escaping the host immune response against it. HIV is transmitted primarily through blood and genital fluids and to newborn infants from infected mothers. The steps occurring in infection involve an interaction of HIV not only with the CD4 molecule on cells but also with other cellular receptors recently identified. Virus-cell fusion and HIV entry subsequently take place. Following virus infection, a variety of intracellular mechanisms determine the relative expression of viral regulatory and accessory genes leading to productive or latent infection. With CD4+ lymphocytes, HIV replication can cause syncytium formation and cell death; with other cells, such as macrophages, persistent infection can occur, creating reservoirs for the virus in many cells and tissues. HIV strains are highly heterogeneous, and certain biologic and serologic properties determined by specific genetic sequences can be linked to pathogenic pathways and resistance to the immune response. The host reaction against HIV, through neutralizing antibodies and particularly through strong cellular immune responses, can keep the virus suppressed for many years. Long-term survival appears to involve infection with a relatively low-virulence strain that remains sensitive to the immune response, particularly to control by CD8+ cell antiviral activity. Several therapeutic approaches have been attempted, and others are under investigation. Vaccine development has provided some encouraging results, but the observations indicate the major challenge of preventing infection by HIV. Ongoing research is necessary to find a solution to this devastating worldwide epidemic. Images PMID:8464405

  7. Human immunodeficiency virus induced oral candidiasis.

    PubMed

    Warrier, S Aravind; Sathasivasubramanian, S

    2015-08-01

    Human immunodeficiency virus (HIV) infection is a worldwide health problem, which affects in both developing and developed countries. The oral lesions caused due to this disease can drastically change the life of the patient, in terms of quality. We can also know the progression of the disease and also the important immune status of the patient. Lots of information on HIV is known in the developed countries and very less reports are available in the developing countries. The morbidity of HIV disease is due to its association with opportunistic fungal infection and the most common among them is oral candidiasis. Here, we present a case report on an apparently healthy male patient of 39 years, who had oral candidiasis and was one of the indicators for HIV infection.

  8. Evolution of feline immunodeficiency virus Gag proteins.

    PubMed

    Burkala, Evan; Poss, Mary

    2007-10-01

    We evaluated the predicted biochemical properties of Gag proteins from a diverse group of feline immunodeficiency viruses (FIV) to determine how different evolutionary histories of virus and host have changed or constrained these important structural proteins. Our data are based on FIV sequences derived from domestic cat (FIVfca), cougar (FIVpco), and lions (FIVple). Analyses consisted of determining the selective forces acting at each position in the protein and the comparing predictions for secondary structure, charge, hydrophobicity and flexibility for matrix, capsid and nucleocapsid, and the C-terminal peptide, which comprise the Gag proteins. We demonstrate that differences among the FIV Gag proteins have largely arisen by neutral evolution, although many neutrally evolving regions have maintained biochemical features. Regions with predicted differences in biochemical features appear to involve intramolecular interactions and structural elements that undergo conformational changes during particle maturation. In contrast, the majority of sites involved in intermolecular contacts on the protein surface are constrained by purifying selection. There is also conservation of sites that interact with host proteins associated with cellular trafficking and particle budding. NC is the only protein with evidence of positive selection, two of which occur in the N-terminal region responsible for RNA binding and interaction with host proteins.

  9. Simian immunodeficiency virus infection of CD8+ lymphocytes in vivo.

    PubMed Central

    Dean, G A; Reubel, G H; Pedersen, N C

    1996-01-01

    To determine the lymphoid target cells of simian immunodeficiency virus (SIV) in vivo, peripheral blood lymphocytes (PBL) and lymph node lymphocytes (LNL) were positively selected (>97% purity) for surface expression of CD4, CD8, or CD20 and then analyzed for SIV provirus using semiquantitative DNA amplification. We found provirus in CD4+ and CD8+ lymphocytes but none in CD20+ lymphocytes. During acute SIV infection (< or = 214 days postinoculation), the percentage of PBL and LNL CD4+ cells containing proviral DNA ranged from 0.2 to 20% and from 0.2 to 2%, respectively. Proviral burden in the CD8+ population of either PBL or LNL ranged from 0.01 to 0.2%. Virus isolation by cocultivation was positive for both CD4+ and CD8+ purified populations. No difference in proviral burden was observed between PBL and LNL subsets during acute SIV infection. Up to 19.4% of positively selected CD8+ cells also expressed CD4, and thus the provirus may reside within a dual-positive population. This dual-positive population may represent activated lymphocytes that are particularly susceptible to infection and may provide an opportunity for virus entry into the CD8+ CD4- lymphocytes in vivo. PMID:8764081

  10. Epstein-Barr and human immunodeficiency viruses in acquired immunodeficiency syndrome-related primary central nervous system lymphoma.

    PubMed Central

    Morgello, S.

    1992-01-01

    The prevalence of Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) in acquired immunodeficiency syndrome (AIDS)-related primary central nervous system (CNS) lymphoma was examined. Deoxyribonucleic acid (DNA) extracted from 12 formalin-fixed, paraffin-embedded tumors was used as substrate for the polymerase chain reaction (PCR). Targets for amplification were the EBNA-1 region of EBV, the gag region of HIV, and a single copy cellular sequence as a control. The cases studied were autopsy and surgical specimens collected between the years 1985 and 1989. By the working formulation for non-Hodgkin's lymphomas, five had large cell, four had mixed large and small cleaved cell, two had small cleaved cell, and one had an unclassified histology. Epstein-Barr virus was detected in 6 of 12 tumors studied. Human immunodeficiency virus was not detected in any of the tumors. The presence of EBV was not correlated with any particular histologic tumor type. It is concluded that EBV, not HIV, can be detected in a large percentage (50%) of AIDS-related primary central nervous system (CNS) lymphomas. This viral association may be significant in light of the demonstrated ability of EBV to induce lymphoid tumors in experimental mammalian systems. Images Figure 1 Figure 2 PMID:1323221

  11. Crystals of a ternary complex of human immunodeficiency virus type 1 reverse transcriptase with a monoclonal antibody Fab fragment and double-stranded DNA diffract x-rays to 3.5-A resolution.

    PubMed Central

    Jacobo-Molina, A; Clark, A D; Williams, R L; Nanni, R G; Clark, P; Ferris, A L; Hughes, S H; Arnold, E

    1991-01-01

    Two crystal forms of complexes have been grown that contain human immunodeficiency virus type 1 reverse transcriptase and a monoclonal antibody Fab fragment. One of the crystal forms (form II, space group P3112, a = 168.7 A, c = 220.3 A) diffracts x-rays to 3.5-A resolution and appears suitable for moderate-resolution structure determination. The form II crystals have the unusual property that their maximum resolution of diffraction and resistance to radiation damage are enhanced by either crystallization in the presence of or soaking with double-stranded DNA primer-template mimics. These crystals may permit structural studies of catalytically relevant complexes and eventually enable us to experimentally observe successive steps in the reverse transcription process. Images PMID:1720554

  12. [Cerebral infarction in human immunodeficiency virus infection].

    PubMed

    Blanche, P; Toulon, P; de La Blanchardière, A; Sicard, D

    1995-06-01

    Patients infected with the human immunodeficiency virus (HIV) appear to have a high risk of ischaemic cerebral events. We observed two cases of cerebral infarction in patients with acquired immune deficiency syndrome (AIDS). In the first case, a 38-year-old homosexual with no cardiovascular risk other than smoking presented with rapidly progressive hemiparesia. Brain CT-scan visualized two infarcts in the territory of the right sylvian artery and the arteriography an occlusion of the internal carotid artery. In the second, a 37-year-old homosexual, hospitalization was required for a left-sided pure sensitive epilepsy seizure. There was no cardiovascular risk other than smoking. Magnetic resonance imaging showed parietal ischaemia and thrombus in the left atrium without atrial hypertrophy was seen at transoesophageal echocardiography. In both cases, there was no evidence of endocarditis, dissection of the neck vessels or disseminated intravascular coagulation nor of associated viral or bacterial infectious complication of AIDS. Angiographic findings eliminated cerebral vascularitis. Among the perturbed haemostasis factors previously reported in HIV+ patients, we observed free proteins S deficiency (68 and 43%) and heparin cofactor II deficiency (54 and 40%). Serum albumin was 33 and 32 g/l respectively. Outcome was favourable in both cases with anticoagulant therapy. These coagulation anomalies would not appear sufficient to explain cerebral infarction. Other mechanisms including immune complexed deposition, direct HIV toxicity for endothelial cells or the effect of cytokines on smooth muscles fibres and fibroblasts are probably more important causal factors. PMID:7638144

  13. Anti-(human immunodeficiency virus) activity of polyoxotungstates and their inhibition of human immunodeficiency virus reverse transcriptase.

    PubMed Central

    Moore, P S; Jones, C J; Mahmood, N; Evans, I G; Goff, M; Cooper, R; Hay, A J

    1995-01-01

    Heteropolyoxotungstates of the Keggin class containing different heteroatoms were tested for inhibition of two strains of human immunodeficiency virus 1 (HIV-1); they exhibited varying antiviral activity. Compounds containing boron were inactive, only one of those containing phosphorus showed selective anti-viral activity, whereas all silicon-containing compounds exhibited significant anti-viral activity in C8166 cells infected with the IIIB strain. Their effectiveness was some 10-fold higher in JM cells with selectivity indices of about 2000. The silicotungstates were effective inhibitors of HIV reverse transcriptase, showing greater inhibition with RNA/DNA template primers than with DNA/DNA template.primer. Kinetic analysis demonstrated that they inhibit the enzyme by different mechanisms, as, of the four compounds examined, two competed with template.primer and two competed with deoxynucleoside triphosphate. Inhibition of DNA polymerase activity by these compounds was compared using polymerases from different sources, including human; although not necessarily most specific for HIV-1 reverse transcriptase, they did not inhibit all DNA polymerases to a similar degree. PMID:7536411

  14. Immunogenicity of a vaccine regimen composed of simian immunodeficiency virus DNA, rMVA, and viral particles administered to female rhesus macaques via four different mucosal routes.

    PubMed

    Manrique, Mariana; Kozlowski, Pamela A; Cobo-Molinos, Antonio; Wang, Shainn-Wei; Wilson, Robert L; Montefiori, David C; Carville, Angela; Aldovini, Anna

    2013-04-01

    A comparative evaluation of the immunity stimulated with a vaccine regimen that includes simian immunodeficiency virus (SIV), interleukin 2 (IL-2), and IL-15 DNAs, recombinant modified vaccinia virus Ankara (rMVA), and inactivated SIVmac239 particles administered into the oral and nasal cavities, small intestine, and vagina was carried out in female rhesus macaques to determine the best route to induce diverse anti-SIV immunity that may be critical to protection from SIV infection and disease. All four immunizations generated mucosal SIV-specific IgA. Oral immunization was as effective as vaginal immunization in inducing SIV-specific IgA in vaginal secretions and generated greater IgA responses in rectal secretions and saliva samples compared to the other immunization routes. All four immunizations stimulated systemic T-cell responses against Gag and Env, albeit to a different extent, with oral immunization providing greater magnitude and nasal immunization providing wider functional heterogeneity. SIV-specific T cells producing gamma interferon (IFN-γ) dominated these responses. Limited levels of SIV-specific IgG antibodies were detected in plasma samples, and no SIV-specific IgG antibodies were detected in secretions. Vaccination also induced CD4(+) and CD8(+) T-cell responses in the rectal and vaginal mucosa with greater functional heterogeneity than in blood samples. Rectal T-cell responses were significantly greater in the orally vaccinated animals than in the other animals. The most balanced, diverse, and higher-magnitude vaginal T-cell responses were observed after intestinal vaccination. Significantly higher CD8(+) granzyme B-positive T-cell responses were observed systemically after intestinal vaccination and in rectal cells after oral immunization. The majority of SIV-specific T cells that produced granzyme B did not produce cytokines. Of the immunization routes tested, oral vaccination provided the most diverse and significant response to the vaccine.

  15. Induction of human immunodeficiency virus type-1-specific immunity with a novel gene transport unit (GTU)-MultiHIV DNA vaccine.

    PubMed

    Blazevic, Vesna; Männik, Andres; Malm, Maria; Sikut, Rein; Valtavaara, Minna; Toots, Urve; Ustav, Mart; Krohn, Kai

    2006-07-01

    A multiHIV fusion gene expressing an antigenic fusion protein composed of regulatory HIV-1 proteins Rev, Nef, and Tat, as well as Gag p17/p24 and a stretch of 11 cytotoxic T lymphocyte (CTL) epitope clusters from Pol and Env, was cloned into a novel DNA vector named the Gene Transport Unit (GTU). A mouse H-2(d)-restricted HIV-1 gp120 epitope (RGPGRAFVTI) was cloned into the fusion gene as well. In addition to the HIV- 1 genes the GTU codes for a nuclear anchoring protein (bovine papilloma virus E2), ensuring the long maintenance of the vector and a high expression level of the selected immunogens. BALB/c mice were immunized with the GTU-MultiHIV DNA construct by different routes and regimens of immunization to assess the immunogenicity of the DNA vaccine in vivo. Mice developed strong CD8(+) CTL responses to HIV-1 Env and Gag measured by an ELISPOT-IFN-gamma assay and chromium release assay. In addition, T cell responses to regulatory proteins Rev, Nef, and Tat were induced. Antibody responses were detected to each of the HIV antigens encoded by the DNA construct. Minimal doses of the GTU-MultiHIV DNA delivered by gene gun were potent in inducing significant HIV-specific CTL responses. The equivalent doses of the conventional plasmid expressing MultiHIV DNA delivered by gene gun failed to do so. An ideal DNA vaccine should yield high expression of the viral antigens for a prolonged period of time, and expression of the multiple viral antigens is probably required for the induction of a broad and protective immune response. The GTU-MultiHIV DNA vaccine described is a good vaccine candidate that meets the above criteria. PMID:16831091

  16. Immunoassay for detection of antibodies to simian immunodeficiency virus and human immunodeficiency virus in serum.

    PubMed

    Otsyula, M G; Yee, J A; Suleman, M A; Marx, P A; Jennings, M B

    1996-04-01

    We developed a simple, inexpensive, rapid assay for the detection of antibodies to simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) in serum. The immunoassay uses inactivated SIV and HIV-1 gp41 transmembrane recombinant protein as antigenic adsorbents on a nitrocellulose filter membrane. Diluted serum, with the addition of Protein-A-Gold, is gravity-filtered through the filter membrane, blocked, and buffer-washed. Antibodies to HIV or SIV or both in serum bind to the appropriate antigen, and the resulting antigen-antibody complex reacts with Protein-A-Gold to produce a readable pink color. Field evaluation of the test on 30 human and 70 nonhuman primate sera in Kenya and Zaire indicated that the test had at least 93 and 90% correlation with Western blot sensitivity and specificity respectively. Prior refrigeration of the test kit and incubation of sera during testing were not required. This result indicates that the test may be a rapid, economical, and simple test for detecting HIV, SIV, or both in serum. This immunoassay can be useful for carrying out HIV and SIV serosurveys in countries with limited or no laboratory facilities. PMID:8723237

  17. Analysis of the human immunodeficiency virus-1 RNA packageome.

    PubMed

    Eckwahl, Matthew J; Arnion, Helene; Kharytonchyk, Siarhei; Zang, Trinity; Bieniasz, Paul D; Telesnitsky, Alice; Wolin, Sandra L

    2016-08-01

    All retroviruses package cellular RNAs into virions. Studies of murine leukemia virus (MLV) revealed that the major host cell RNAs encapsidated by this simple retrovirus were LTR retrotransposons and noncoding RNAs (ncRNAs). Several classes of ncRNAs appeared to be packaged by MLV shortly after synthesis, as precursors to tRNAs, small nuclear RNAs, and small nucleolar RNAs were all enriched in virions. To determine the extent to which the human immunodeficiency virus (HIV-1) packages similar RNAs, we used high-throughput sequencing to characterize the RNAs within infectious HIV-1 virions produced in CEM-SS T lymphoblastoid cells. We report that the most abundant cellular RNAs in HIV-1 virions are 7SL RNA and transcripts from numerous divergent and truncated members of the long interspersed element (LINE) and short interspersed element (SINE) families of retrotransposons. We also detected precursors to several tRNAs and small nuclear RNAs as well as transcripts derived from the ribosomal DNA (rDNA) intergenic spacers. We show that packaging of a pre-tRNA requires the nuclear export receptor Exportin 5, indicating that HIV-1 recruits at least some newly made ncRNAs in the cytoplasm. Together, our work identifies the set of RNAs packaged by HIV-1 and reveals that early steps in HIV-1 assembly intersect with host cell ncRNA biogenesis pathways. PMID:27247436

  18. The Human Immunodeficiency Virus: Infectivity and Mechanisms of Pathogenesis.

    ERIC Educational Resources Information Center

    Fauci, Anthony S.

    1988-01-01

    Discusses how the infection of the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus, as well as neuropsychiatric abnormalities in the brain. (TW)

  19. Activities of the feline immunodeficiency virus integrase protein produced in Escherichia coli.

    PubMed Central

    Vink, C; van der Linden, K H; Plasterk, R H

    1994-01-01

    Retroviral DNA integration requires the activity of at least one viral protein, the integrase (IN) protein. We cloned and expressed the integrase gene of feline immunodeficiency virus (FIV) in Escherichia coli as a fusion to the malE gene and purified the IN fusion protein by affinity chromatography. The protein is active in site-specific cleavage of the viral DNA ends, DNA strand transfer, and disintegration. FIV IN has a relaxed viral DNA substrate requirement: it cleaves and integrates FIV DNA termini, human immunodeficiency virus DNA ends, and Moloney murine leukemia virus DNA ends with high efficiencies. In the cleavage reaction, IN exposes a specific phosphodiester bond near the viral DNA end to nucleophilic attack. In vitro, either H2O, glycerol, or the 3' OH group of the viral DNA terminus can serve as nucleophile in this reaction. We found that FIV IN preferentially uses the 3' OH ends of the viral DNA as nucleophile, whereas HIV IN protein preferentially uses H2O and glycerol as nucleophiles. Images PMID:8107210

  20. Neuromuscular complications of human immunodeficiency virus infection and antiretroviral therapy.

    PubMed Central

    Miller, R G

    1994-01-01

    At least 4 distinct peripheral neuropathy syndromes occur in patients infected with the human immunodeficiency virus. The most common, painful sensory neuropathy, may be related to the viral infection or may be medication induced and is treated symptomatically. The other 3, chronic inflammatory demyelinating polyradiculoneuropathy, mononeuropathy multiplex (some patients), and the progressive polyradiculopathies related to the acquired immunodeficiency syndrome, may all respond to appropriate therapy. Both inflammatory myopathy and zidovudine myopathy also abate with early diagnosis and treatment. PMID:8048229

  1. Molecular and biological aspects of the bovine immunodeficiency virus.

    PubMed

    Corredor, Andrea G; St-Louis, Marie-Claude; Archambault, Denis

    2010-01-01

    The bovine immunodeficiency virus (BIV) was isolated in 1969 from a cow, R-29, with a wasting syndrome suggesting bovine leucosis. The virus, first designated bovine visna-like virus, remained unstudied until HIV was discovered in 1983. Then, it was demonstrated in 1987 that the bovine R-29 isolate was a lentivirus with striking similarity to the human immunodeficiency virus (HIV). Moreover, BIV has the most complex genomic structure among all identified lentiviruses shown by several regulatory/accessory genes encoding proteins, some of which are involved in the regulation of virus gene expression. This manuscript aims to review biological and molecular aspects of BIV, with emphasis on regulatory/accessory viral genes/proteins which are involved in virus expression. PMID:20210777

  2. Human immunodeficiency virus, herpes virus infections, and pulmonary vascular disease

    PubMed Central

    Flores, Sonia C.; Almodovar, Sharilyn

    2013-01-01

    The following state-of-the-art seminar was delivered as part of the Aspen Lung Conference on Pulmonary Hypertension and Vascular Diseases held in Aspen, Colorado in June 2012. This paper will summarize the lecture and present results from a nonhuman primate model of infection with Simian (Human) Immunodeficiency Virus - nef chimeric virions as well as the idea that polymorphisms in the HIV-1 nef gene may be driving the immune response that results in exuberant inflammation and aberrant endothelial cell (EC) function. We will present data gathered from primary HIV nef isolates where we tested the biological consequences of these polymorphisms and how their presence in human populations may predict patients at risk for developing this disease. In this article, we also discuss how a dysregulated immune system, in conjunction with a viral infection, could contribute to pulmonary arterial hypertension (PAH). Both autoimmune diseases and some viruses are associated with defects in the immune system, primarily in the function of regulatory T cells. These T-cell defects may be a common pathway in the formation of plexiform lesions. Regardless of the route by which viruses may lead to PAH, it is important to recognize their role in this rare disease. PMID:23662195

  3. In vitro activation of T lymphocytes from human immunodeficiency virus (HIV)-seropositive blood donors. I. Soluble interleukin 2 receptor (IL2R) production parallels cellular IL2R expression and DNA synthesis.

    PubMed

    Prince, H E; Kleinman, S H; Maino, V C; Jackson, A L

    1988-03-01

    We investigated the relationship of soluble interleukin 2 receptor (sIL2R) production to cellular IL2R expression and DNA synthesis by mitogen-stimulated mononuclear cells from blood donors seropositive for human immunodeficiency virus (HIV). SIL2R was measured using an enzyme-linked immunosorbent assay which employed 2 anti-IL2R monoclonal antibodies recognizing distinct IL2R epitopes. Decreased phytohemagglutinin-induced DNA synthesis and cellular IL2R expression were accompanied by decreased levels of sIL2R in cell culture supernatants. Similar findings were observed for pokeweed mitogen-induced responses. There was no detectable spontaneous secretion of sIL2R into culture supernatants by unstimulated mononuclear cells from either HIV-seropositive or control seronegative donors. These findings indicate that the in vitro T-cell activation defects which characterize HIV infection include decreased sIL2R production, as well as decreased cellular IL2R expression and DNA synthesis. Further, they show that assessment of supernatant sIL2R levels can be used as a valid, reliable assay for T-cell activation.

  4. Spatial analysis of feline immunodeficiency virus infection in cougars.

    PubMed

    Wheeler, David C; Waller, Lance A; Biek, Roman

    2010-07-01

    The cougar (Puma concolor) is a large predatory feline found widely in the Americas that is susceptible to feline immunodeficiency virus (FIV), a fast-evolving lentivirus found in wild feline species that is analogous to simian immunodeficiency viruses in wild primates and belongs to the same family of viruses as human immunodeficiency virus. FIV infection in cougars can lead to a weakened immune system that creates opportunities for other infecting agents. FIV prevalence and lineages have been studied previously in several areas in the western United States, but typically without spatially explicit statistical techniques. To describe the distribution of FIV in a sample of cougars located in the northern Rocky Mountain region of North America, we first used kernel density ratio estimation to map the log relative risk of FIV. The risk surface showed a significant cluster of FIV in northwestern Montana. We also used Bayesian cluster models for genetic data to investigate the spatial structure of the feline immunodeficiency virus with virus genetic sequence data. A result of the models was two spatially distinct FIV lineages that aligned considerably with an interstate highway in Montana. Our results suggest that the use of spatial information and models adds novel insight when investigating an infectious animal disease. The results also suggest that the influence of landscape features likely plays an important role in the spatiotemporal spread of an infectious disease within wildlife populations.

  5. Spatial Analysis of Feline Immunodeficiency Virus Infection in Cougars

    PubMed Central

    Wheeler, David C.; Waller, Lance A.; Biek, Roman

    2010-01-01

    The cougar (Puma concolor) is a large predatory feline found widely in the Americas that is susceptible to feline immunodeficiency virus (FIV), a fast-evolving lentivirus found in wild feline species that is analogous to simian immunodeficiency viruses in wild primates and belongs to the same family of viruses as human immunodeficiency virus. FIV infection in cougars can lead to a weakened immune system that creates opportunities for other infecting agents. FIV prevalence and lineages have been studied previously in several areas in the western United States, but typically without spatially explicit statistical techniques. To describe the distribution of FIV in a sample of cougars located in the northern Rocky Mountain region of North America, we first used kernel density ratio estimation to map the log relative risk of FIV. The risk surface showed a significant cluster of FIV in northwestern Montana. We also used Bayesian cluster models for genetic data to investigate the spatial structure of the feline immunodeficiency virus with virus genetic sequence data. A result of the models was two spatially distinct FIV lineages that aligned considerably with an interstate highway in Montana. Our results suggest that the use of spatial information and models adds novel insight when investigating an infectious animal disease. The results also suggest that the influence of landscape features likely plays an important role in the spatiotemporal spread of an infectious disease within wildlife populations. PMID:21197421

  6. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Human immunodeficiency virus (HIV) âlookbackâ... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV)...

  7. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Human immunodeficiency virus (HIV) âlookbackâ... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV)...

  8. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Human immunodeficiency virus (HIV) âlookbackâ... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV)...

  9. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Human immunodeficiency virus (HIV) âlookbackâ... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV)...

  10. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Human immunodeficiency virus (HIV) âlookbackâ... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV)...

  11. Tumorigenic DNA viruses

    SciTech Connect

    Klein, G.

    1989-01-01

    The eighth volume of Advances in Viral Oncology focuses on the three major DNA virus groups with a postulated or proven tumorigenic potential: papillomaviruses, animal hepatitis viruses, and the Epstein-Bar virus. In the opening chapters, the contributors analyze the evidence that papillomaviruses and animal hepatitis viruses are involved in tumorigenesis and describe the mechanisms that trigger virus-host cell interactions. A detailed section on the Epstein-Barr virus (EBV) - comprising more than half the book - examines the transcription and mRNA processing patterns of the virus genome; the mechanisms by which EBV infects lymphoid and epithelial cells; the immunological aspects of the virus; the actions of EBV in hosts with Acquired Immune Deficiency Syndrome; and the involvement of EBV in the etiology of Burkitt's lymphoma.

  12. Functional role of human immunodeficiency virus type 1 vpu.

    PubMed Central

    Terwilliger, E F; Cohen, E A; Lu, Y C; Sodroski, J G; Haseltine, W A

    1989-01-01

    To investigate the role of vpu in the replication and cytopathicity of human immunodeficiency virus type 1 (HIV-1), infectious proviruses were constructed that were isogenic except for the ability to produce the protein product of vpu. The vpu-encoded protein is shown to decrease the rate of syncytium formation and cell killing in infected CD4+ human T cells, to increase greatly the export of virus particles from infected cells, and to reduce the rate of accumulation of cell-associated viral proteins. The vpu protein complements in trans the defect in a vpu- HIV-1 provirus but does not affect the simian immunodeficiency virus, which lacks vpu. These observations suggest that vpu may contribute to the AIDS epidemic by increasing the transmission efficiency of the virus. Images PMID:2472639

  13. Frequent transmission of immunodeficiency viruses among bobcats and pumas

    USGS Publications Warehouse

    Franklin, S.P.; Troyer, J.L.; TerWee, J.A.; Lyren, L.M.; Boyce, W.M.; Riley, S.P.D.; Roelke, M.E.; Crooks, K.R.; VandeWoude, S.

    2007-01-01

    With the exception of human immunodeficiency virus (HIV), which emerged in humans after cross-species transmissions of simian immunodeficiency viruses from nonhuman primates, immunodeficiency viruses of the family Lentiviridae represent species-specific viruses that rarely cross species barriers to infect new hosts. Among the Felidae, numerous immunodeficiency-like lentiviruses have been documented, but only a few cross-species transmissions have been recorded, and these have not been perpetuated in the recipient species. Lentivirus seroprevalence was determined for 79 bobcats (Lynx rufus) and 31 pumas (Puma concolor) from well-defined populations in Southern California. Partial genomic sequences were subsequently obtained from 18 and 12 seropositive bobcats and pumas, respectively. Genotypes were analyzed for phylogenic relatedness and genotypic composition among the study set and archived feline lentivirus sequences. This investigation of feline immunodeficiency virus infection in bobcats and pumas of Southern California provides evidence that cross-species infection has occurred frequently among these animals. The data suggest that transmission has occurred in multiple locations and are most consistent with the spread of the virus from bobcats to pumas. Although the ultimate causes remain unknown, these transmission events may occur as a result of puma predation on bobcats, a situation similar to that which fostered transmission of HIV to humans, and likely represent the emergence of a lentivirus with relaxed barriers to cross-species transmission. This unusual observation provides a valuable opportunity to evaluate the ecological, behavioral, and molecular conditions that favor repeated transmissions and persistence of lentivirus between species. Copyright ?? 2007, American Society for Microbiology. All Rights Reserved.

  14. Human Immunodeficiency Virus Associated Sporadic Nonfamilial Porphyria Cutanea Tarda.

    PubMed

    Guha, Sibashish Kamal; Bandyopadhyay, Debabrata; Saha, Abanti; Lal, Niharika Ranjan

    2016-01-01

    Porphyria cutanea tarda (PCT), a relatively uncommon metabolic disease, is the most common cutaneous porphyria. Here, we present the case of a patient diagnosed with sporadic, nonfamilial PCT that presented with classical cutaneous findings and multiple risk factors, including alcohol abuse, human immunodeficiency virus/AIDS, that have been strongly associated with the sporadic form of PCT. PMID:27293254

  15. Titration of feline immunodeficiency virus-based lentiviral vector preparations.

    PubMed

    Saenz, Dyana T; Barraza, Román; Loewen, Nils; Teo, Wulin; Poeschla, Eric M

    2012-01-01

    Feline immunodeficiency virus (FIV)-based lentiviral vectors are useful for introducing integrated transgenes into nondividing human cells. This protocol describes methods for measuring and calculating vector titers in transducing units (TU)/mL. Alternate methods are provided for green fluorescent protein (GFP) vectors and for β-galactosidase vectors.

  16. Human Immunodeficiency Virus Associated Sporadic Nonfamilial Porphyria Cutanea Tarda

    PubMed Central

    Guha, Sibashish Kamal; Bandyopadhyay, Debabrata; Saha, Abanti; Lal, Niharika Ranjan

    2016-01-01

    Porphyria cutanea tarda (PCT), a relatively uncommon metabolic disease, is the most common cutaneous porphyria. Here, we present the case of a patient diagnosed with sporadic, nonfamilial PCT that presented with classical cutaneous findings and multiple risk factors, including alcohol abuse, human immunodeficiency virus/AIDS, that have been strongly associated with the sporadic form of PCT. PMID:27293254

  17. Nontyphoidal Salmonellosis, Human Immunodeficiency Virus Infection, and Ischemic Stroke

    PubMed Central

    Piggott, Damani A.; Carroll, Karen C.; Lim, Michael; Melia, Michael T.

    2016-01-01

    Nontyphoidal Salmonella infection and stroke are major causes of morbidity and mortality worldwide, with increased risk in the human immunodeficiency virus (HIV)-infected population. We report a rare case of ischemic stroke associated with Salmonella enteritidis subdural empyema in an older HIV-infected patient with multimorbidity, despite surgery and treatment with susceptible antimicrobial drugs. PMID:27419176

  18. [Pulmonary arterial hypertension associated to human immunodeficiency virus].

    PubMed

    Sandoval-Gutiérrez, José Luis; Santos-Martínez, Luis Efren; Rodríguez-Silverio, Juan; Baranda-Tovar, Francisco Martín; Rivera-Rosales, Rosa María; Flores-Murrieta, Francisco Javier

    2015-01-01

    From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future. PMID:25577549

  19. [Pulmonary arterial hypertension associated to human immunodeficiency virus].

    PubMed

    Sandoval-Gutiérrez, José Luis; Santos-Martínez, Luis Efren; Rodríguez-Silverio, Juan; Baranda-Tovar, Francisco Martín; Rivera-Rosales, Rosa María; Flores-Murrieta, Francisco Javier

    2015-01-01

    From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future.

  20. Symptoms of Autonomic Dysfunction in Human Immunodeficiency Virus

    PubMed Central

    Chow, Dominic; Nakamoto, Beau K.; Sullivan, Katherine; Sletten, David M.; Fujii, Satomi; Umekawa, Sari; Kocher, Morgan; Kallianpur, Kalpana J.; Shikuma, Cecilia M.; Low, Phillip

    2015-01-01

    This retrospective study evaluated the frequencies of symptoms associated with autonomic dysfunction in human immunodeficiency virus (HIV)-infected patients on stable combined antiretroviral therapy. Patients infected with HIV reported higher frequencies of dysautonomia symptoms compared with HIV-negative patients, particularly in the autonomic domains related to urinary, sleep, gastroparesis, secretomotor, pupillomotor, and male sexual dysfunction. PMID:26269797

  1. The Presidential Commission on the Human Immunodeficiency Virus Epidemic Report.

    ERIC Educational Resources Information Center

    Presidential Commission on the Human Immunodeficiency Virus Epidemic, Washington, DC.

    This document presents findings of the Presidential Commission on the Human Immunodeficiency Virus (HIV) epidemic. The executive summary lists 20 major findings and recommendations which together comprise a comprehensive national strategy for managing the HIV epidemic. The commission recommends: (1) replacement of the obsolete term "AIDS"…

  2. Nontyphoidal Salmonellosis, Human Immunodeficiency Virus Infection, and Ischemic Stroke.

    PubMed

    Piggott, Damani A; Carroll, Karen C; Lim, Michael; Melia, Michael T

    2016-04-01

    Nontyphoidal Salmonella infection and stroke are major causes of morbidity and mortality worldwide, with increased risk in the human immunodeficiency virus (HIV)-infected population. We report a rare case of ischemic stroke associated with Salmonella enteritidis subdural empyema in an older HIV-infected patient with multimorbidity, despite surgery and treatment with susceptible antimicrobial drugs. PMID:27419176

  3. Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome.

    PubMed

    Monaco, Cynthia L; Gootenberg, David B; Zhao, Guoyan; Handley, Scott A; Ghebremichael, Musie S; Lim, Efrem S; Lankowski, Alex; Baldridge, Megan T; Wilen, Craig B; Flagg, Meaghan; Norman, Jason M; Keller, Brian C; Luévano, Jesús Mario; Wang, David; Boum, Yap; Martin, Jeffrey N; Hunt, Peter W; Bangsberg, David R; Siedner, Mark J; Kwon, Douglas S; Virgin, Herbert W

    2016-03-01

    Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression. PMID:26962942

  4. Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome.

    PubMed

    Monaco, Cynthia L; Gootenberg, David B; Zhao, Guoyan; Handley, Scott A; Ghebremichael, Musie S; Lim, Efrem S; Lankowski, Alex; Baldridge, Megan T; Wilen, Craig B; Flagg, Meaghan; Norman, Jason M; Keller, Brian C; Luévano, Jesús Mario; Wang, David; Boum, Yap; Martin, Jeffrey N; Hunt, Peter W; Bangsberg, David R; Siedner, Mark J; Kwon, Douglas S; Virgin, Herbert W

    2016-03-01

    Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression.

  5. Human Immunodeficiency Virus Type 1 Infection of Neural Xenografts

    NASA Astrophysics Data System (ADS)

    Cvetkovich, Therese A.; Lazar, Eliot; Blumberg, Benjamin M.; Saito, Yoshihiro; Eskin, Thomas A.; Reichman, Richard; Baram, David A.; del Cerro, Coca; Gendelman, Howard E.; del Cerro, Manuel; Epstein, Leon G.

    1992-06-01

    Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain.

  6. Human immunodeficiency virus type 1 infection of neural xenografts.

    PubMed Central

    Cvetkovich, T A; Lazar, E; Blumberg, B M; Saito, Y; Eskin, T A; Reichman, R; Baram, D A; del Cerro, C; Gendelman, H E; del Cerro, M

    1992-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain. Images PMID:1594627

  7. Species-Specific, Postentry Barriers to Primate Immunodeficiency Virus Infection

    PubMed Central

    Hofmann, Wolfgang; Schubert, David; LaBonte, Jason; Munson, Linda; Gibson, Susan; Scammell, Jonathan; Ferrigno, Paul; Sodroski, Joseph

    1999-01-01

    By using replication-defective vectors derived from human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIVmac), and murine leukemia virus (MuLV), all of which were pseudotyped with the vesicular stomatitis virus (VSV) G glycoprotein, the efficiency of postentry, early infection events was examined in target cells of several mammalian species. Titers of HIV-1 vectors were significantly lower than those of SIVmac and MuLV vectors in most cell lines and primary cells from Old World monkeys. By contrast, most New World monkey cells exhibited much lower titers for the SIVmac vector compared with those of the HIV-1 vector. Prosimian cells were resistant to both HIV-1 and SIVmac vectors, although the MuLV vector was able to infect these cells. Cells from other mammalian species were roughly equivalent in susceptibility to the three vectors, with the exception of rabbit cells, which were specifically resistant to the HIV-1 vector. The level of HIV-1 vector expression was very low in transduced cells of rodent, rabbit, cow, and pig origin. Early postentry restriction of primate immunodeficiency virus infection exhibits patterns largely coincident with species borders and applies to diverse cell types within an individual host, suggesting the involvement of species-specific, widely expressed cellular factors. PMID:10559316

  8. Sicca complex and infection with human immunodeficiency virus.

    PubMed

    Couderc, L J; D'Agay, M F; Danon, F; Harzic, M; Brocheriou, C; Clauvel, J P

    1987-05-01

    Five male patients with the persistent generalized lymphadenopathy syndrome also had a sicca complex. Salivary gland biopsy specimens showed diffuse lymphocytic infiltration of the glandular parenchyma. Serum autoantibodies and rheumatoid factor were not detected. All patients had IgG antibodies to human immunodeficiency virus and IgG to the viral capsid antigen of Epstein-Barr virus. These five patients had benign lymphocytic infiltrates in other organs (lung, liver, and kidneys). Sicca complex may be one of the various manifestations of the lymphoid hyperplasia noted in human immunodeficiency virus-infected patients. In these patients, the sicca complex showed specific features related to male predominance, lack of serum autoantibodies, and peripheral-blood T-lymphocyte subset distribution.

  9. Hemophagocytic Lymphohistiocytosis Secondary to Human Immunodeficiency Virus-Associated Histoplasmosis

    PubMed Central

    Castelli, Anthony A.; Rosenthal, David G.; Bender Ignacio, Rachel; Chu, Helen Y.

    2015-01-01

    Hemophagocytic lymphohistiocytosis (HLH) in immunocompromised hosts is a fulminant syndrome of immune activation with high rates of mortality that may be triggered by infections or immunodeficiency. Rapid diagnosis and treatment of the underlying disorder is necessary to prevent progression to multiorgan failure and death. We report a case of HLH in a patient with human immunodeficiency virus, disseminated histoplasmosis, Mycobacterium avium complex, and Escherichia coli bacteremia. We discuss management of acutely ill patients with HLH and treatment of the underlying infection versus initiation of HLH-specific chemotherapy. PMID:26566535

  10. Spinal cord toxoplasmosis in human immunodeficiency virus infection/acquired immunodeficiency syndrome.

    PubMed

    García-García, Concepción; Castillo-Álvarez, Federico; Azcona-Gutiérrez, José M; Herraiz, María J; Ibarra, Valvanera; Oteo, José A

    2015-05-01

    Neurological complications in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) are still common, even in the era of highly active antiretroviral therapy. Opportunistic infections, immune reconstitution, the virus itself, antiretroviral drugs and neurocognitive disorders have to be considered when establishing the differential diagnosis. Toxoplasmic encephalitis remains the major cause of space-occupying lesions in the brain of patients with HIV/AIDS; however, spinal cord involvement has been reported infrequently. Here, we review spinal cord toxoplasmosis in HIV infection and illustrate the condition with a recent case from our hospital. We suggest that most patients with HIV/AIDS and myelitis with enhanced spine lesions, multiple brain lesions and positive serology for Toxoplasma gondii should receive immediate empirical treatment for toxoplasmosis, and a biopsy should be performed in those cases without clinical improvement or with deterioration.

  11. Simian Immunodeficiency Virus Disease Course Is Predicted by the Extent of Virus Replication during Primary Infection

    PubMed Central

    Staprans, Silvija I.; Dailey, Peter J.; Rosenthal, Ann; Horton, Chris; Grant, Robert M.; Lerche, Nicholas; Feinberg, Mark B.

    1999-01-01

    To elucidate the relationship between early viral infection events and immunodeficiency virus disease progression, quantitative-competitive and branched-DNA methods of simian immunodeficiency virus (SIV) RNA quantitation were cross-validated and used to measure viremia following infection of rhesus macaques with the pathogenic SIVmac251 virus isolate. Excellent correlation between the methods suggests that both accurately approximate SIV copy number. Plasma viremia was evident 4 days postinfection, and rapid viral expansion led to peak viremia levels of 107 to 109 SIV RNA copies/ml by days 8 to 17. Limited resolution of primary viremia was accompanied by relatively short, though variable, times to the development of AIDS (81 to 630 days). The persistent high-level viremia observed following intravenous inoculation of SIVmac251 explains the aggressive disease course in this model. Survival analyses demonstrated that the disease course is established 8 to 17 days postinfection, when peak viremia is observed. The most significant predictor of disease progression was the extent of viral decline following peak viremia; larger decrements in viremia were associated with both lower steady-state viremia (P = 0.0005) and a reduced hazard of AIDS (P = 0.004). The data also unexpectedly suggested that following SIVmac251 infection, animals with the highest peak viremia were better able to control virus replication rather than more rapidly developing disease. Analysis of early viral replication dynamics should help define host responses that protect from disease progression and should provide quantitative measures to assess the extent to which protective responses may be induced by prophylactic vaccination. PMID:10233944

  12. Perinatally infected adolescents living with human immunodeficiency virus (perinatally human immunodeficiency virus)

    PubMed Central

    Cruz, Maria Leticia S; Cardoso, Claudete A

    2015-01-01

    The availability of highly potent antiretroviral treatment during the last decades has transformed human immunodeficiency virus (HIV) infection into a chronic disease. Children that were diagnosed during the first months or years of life and received treatment, are living longer and better and are presently reaching adolescence and adulthood. Perinatally HIV-infected adolescents (PHIV) and young adults may present specific clinical, behavior and social characteristics and demands. We have performed a literature review about different aspects that have to be considered in the care and follow-up of PHIV. The search included papers in the MEDLINE database via PubMed, located using the keywords “perinatally HIV-infected” AND “adolescents”. Only articles published in English or Portuguese from 2003 to 2014 were selected. The types of articles included original research, systematic reviews, and quantitative or qualitative studies; case reports and case series were excluded. Results are presented in the following topics: “Puberal development and sexual maturation”, “Growth in weight and height”, “Bone metabolism during adolescence”, “Metabolic complications”, “Brain development, cognition and mental health”, “Reproductive health”, “Viral drug resistance” and “Transition to adult outpatient care”. We hope that this review will support the work of pediatricians, clinicians and infectious diseases specialists that are receiving these subjects to continue treatment. PMID:26279988

  13. Disinfection of Goldmann tonometers against human immunodeficiency virus type 1.

    PubMed

    Pepose, J S; Linette, G; Lee, S F; MacRae, S

    1989-07-01

    Goldmann tonometer tips were inoculated with 5 X 10(5) IU of cell-free or cell-associated human immunodeficiency virus type 1 (lymphadenopathy virus type 1 isolate) or 10(4) plaque-forming units of herpes simplex virus type 1 (McKrae strain) or type 2 (Hicks strain). In an effort to mimic a "worst case" clinical scenario, each respective virus was allowed to air dry on the tonometer tip for 10 minutes. Inoculated tonometers were then (1) not treated, (2) wiped with a disposable (Kim-wipe) tissue or sterile gauze; (3) wiped with sterile gauze soaked with 3% hydrogen peroxide; or (4) wiped with a 70% isopropyl alcohol swab. The hydrogen peroxide treatment and the alcohol wipes both completely disinfected the tonometer tips for human immunodeficiency virus type 1 and herpes simplex virus types 1 and 2, whereas wiping with a sterile gauze or tissue was not effective. Wiping the Goldmann tonometer tip with an isopropyl alcohol swab and then allowing the alcohol to evaporate provides a ready and efficient means of inactivating these three enveloped viruses.

  14. Multiple effects of mutations in human immunodeficiency virus type 1 integrase on viral replication.

    PubMed Central

    Engelman, A; Englund, G; Orenstein, J M; Martin, M A; Craigie, R

    1995-01-01

    The integration of a DNA copy of the human immunodeficiency virus type 1 (HIV-1) genome into a chromosome of an infected cell is a pivotal step in virus replication. Integration requires the activity of the virus-encoded integrase, which enters the cell as a component of the virion. Results of numerous mutagenesis studies have identified amino acid residues and protein domains of HIV-1 integrase critical for in vitro activity, but only a few of these mutants have been studied for their effects on HIV replication. We have introduced site-directed changes into an infectious DNA clone of HIV-1 and show that integrase mutations can affect virus replication at a variety of steps. We identified mutations that altered virion morphology, levels of particle-associated integrase and reverse transcriptase, and viral DNA synthesis. One replication-defective mutant virus which had normal morphology and protein composition displayed increased levels of circular viral DNA following infection of a T-cell line. This virus also had a significant titer in a CD4-positive indicator cell assay, which requires the viral Tat protein. Although unintegrated viral DNA can serve as a template for Tat expression in infected indicator cells, this level of expression is insufficient to support a spreading viral infection in CD4-positive lymphocytes. PMID:7535863

  15. Interactions of cellular proteins involved in the transcriptional regulation of the human immunodeficiency virus.

    PubMed Central

    Garcia, J A; Wu, F K; Mitsuyasu, R; Gaynor, R B

    1987-01-01

    The human immunodeficiency virus (HIV) is a human retrovirus which is the etiologic agent of the acquired immunodeficiency syndrome. To study the cellular factors involved in the transcriptional regulation of this virus, we performed DNase I footprinting of the viral LTR using partially purified HeLa cell extracts. Five regions of the viral LTR appear critical for DNA binding of cellular proteins. These include the negative regulatory, enhancer, SP1, TATA and untranslated regions. Deletion mutagenesis of these binding domains has significant effects on the basal level of transcription and the ability to be induced by the viral tat protein. Mutations of either the negative regulatory or untranslated regions affect factor binding to the enhancer region. In addition, oligonucleotides complementary to several of the binding domains specifically compete for factor binding. These results suggest that interactions between several distinct cellular proteins are required for HIV transcriptional regulation. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 6. PMID:3428273

  16. Interactions of cellular proteins involved in the transcriptional regulation of the human immunodeficiency virus.

    PubMed

    Garcia, J A; Wu, F K; Mitsuyasu, R; Gaynor, R B

    1987-12-01

    The human immunodeficiency virus (HIV) is a human retrovirus which is the etiologic agent of the acquired immunodeficiency syndrome. To study the cellular factors involved in the transcriptional regulation of this virus, we performed DNase I footprinting of the viral LTR using partially purified HeLa cell extracts. Five regions of the viral LTR appear critical for DNA binding of cellular proteins. These include the negative regulatory, enhancer, SP1, TATA and untranslated regions. Deletion mutagenesis of these binding domains has significant effects on the basal level of transcription and the ability to be induced by the viral tat protein. Mutations of either the negative regulatory or untranslated regions affect factor binding to the enhancer region. In addition, oligonucleotides complementary to several of the binding domains specifically compete for factor binding. These results suggest that interactions between several distinct cellular proteins are required for HIV transcriptional regulation.

  17. Human Immunodeficiency Virus Type 1 Vpr-Binding Protein VprBP, a WD40 Protein Associated with the DDB1-CUL4 E3 Ubiquitin Ligase, Is Essential for DNA Replication and Embryonic Development▿

    PubMed Central

    McCall, Chad M.; Miliani de Marval, Paula L.; Chastain, Paul D.; Jackson, Sarah C.; He, Yizhou J.; Kotake, Yojiro; Cook, Jeanette Gowen; Xiong, Yue

    2008-01-01

    Damaged DNA binding protein 1, DDB1, bridges an estimated 90 or more WD40 repeats (DDB1-binding WD40, or DWD proteins) to the CUL4-ROC1 catalytic core to constitute a potentially large number of E3 ligase complexes. Among these DWD proteins is the human immunodeficiency virus type 1 (HIV-1) Vpr-binding protein VprBP, whose cellular function has yet to be characterized but has recently been found to mediate Vpr-induced G2 cell cycle arrest. We demonstrate here that VprBP binds stoichiometrically with DDB1 through its WD40 domain and through DDB1 to CUL4A, subunits of the COP9/signalsome, and DDA1. The steady-state level of VprBP remains constant during interphase and decreases during mitosis. VprBP binds to chromatin in a DDB1-independent and cell cycle-dependent manner, increasing from early S through G2 before decreasing to undetectable levels in mitotic and G1 cells. Silencing VprBP reduced the rate of DNA replication, blocked cells from progressing through the S phase, and inhibited proliferation. VprBP ablation in mice results in early embryonic lethality. Conditional deletion of the VprBP gene in mouse embryonic fibroblasts results in severely defective progression through S phase and subsequent apoptosis. Our studies identify a previously unknown function of VprBP in S-phase progression and suggest the possibility that HIV-1 Vpr may divert an ongoing chromosomal replication activity to facilitate viral replication. PMID:18606781

  18. Health Administrator Perspectives on Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Prevention and Services at Historically Black Colleges and Universities

    ERIC Educational Resources Information Center

    Warren-Jeanpiere, Lari; Jones, Sandra; Sutton, Madeline Y.

    2011-01-01

    Objective: Due to the disproportionate impact of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) among African American young adults, the authors explored (1) number of historically black college and university (HBCU) campuses with existing HIV prevention policies and services and (2) perceived barriers for implementing…

  19. Severe immunodeficiency associated with a human immunodeficiency virus 1 NEF/3'-long terminal repeat transgene

    PubMed Central

    1994-01-01

    We have generated several transgenic mouse strains carrying a human immunodeficiency virus 1 (HIV-1) NEF/3' long terminal repeat (LTR) transgene under control of a T cell-specific promoter-enhancer element, showing a depletion of CD4+ T cells in the thymus and periphery. The immunological functions of the line with the most dramatic changes in lymphocyte populations, B6/338L, were analyzed in greater detail. The presence of the transgene in the heterozygous animal is associated with a dominant severe immunodeficiency. Older animals develop lymph- adenopathy and splenomegaly. CD4+CD8+ and CD4+CD8- single positive thymocytes already are depleted in these mice at the earliest stages in ontogeny, and peripheral T cells are reduced in frequency and present cell surface marker expression, which is characteristic for memory and activated T cells. The immunological response of B6/338L mice to several viral infections is also greatly impaired. Thus, the HIV-1 NEF/3' LTR as transgene in T cells can cause immunodeficiency and disease with striking similarities to a known retrovirus-induced immunodeficiency called murine AIDS (H. C. Morse III, S. K. Chattopadhyay, M. Makino, T. N. Frederickson, A. W. Hugin, and J. W. Hartley. 1992. AIDS. 6:607). PMID:8113676

  20. Irreversible inhibition of human immunodeficiency virus type 1 integrase by dicaffeoylquinic acids.

    PubMed

    Zhu, K; Cordeiro, M L; Atienza, J; Robinson, W E; Chow, S A

    1999-04-01

    Human immunodeficiency virus type 1 (HIV-1) and other retroviruses require integration of a double-stranded DNA copy of the RNA genome into the host cell chromosome for productive infection. The viral enzyme, integrase, catalyzes the integration of retroviral DNA and represents an attractive target for developing antiretroviral agents. We identified several derivatives of dicaffeoylquinic acids (DCQAs) that inhibit HIV-1 replication in tissue culture and catalytic activities of HIV-1 integrase in vitro. The specific step at which DCQAs inhibit the integration in vitro and the mechanism of inhibition were examined in the present study. Titration experiments with different concentrations of HIV-1 integrase or DNA substrate found that the effect of DCQAs was exerted on the enzyme and not the DNA. In addition to HIV-1, DCQAs also inhibited the in vitro activities of MLV integrase and truncated variants of feline immunodeficiency virus integrase, suggesting that these compounds interacted with the central core domain of integrase. The inhibition on retroviral integrases was relatively specific, and DCQAs had no effect on several other DNA-modifying enzymes and phosphoryltransferases. Kinetic analysis and dialysis experiments showed that the inhibition of integrase by DCQAs was irreversible. The inhibition did not require the presence of a divalent cation and was unaffected by preassembling integrase onto viral DNA. The results suggest that the irreversible inhibition by DCQAs on integrase is directed toward conserved amino acid residues in the central core domain during catalysis.

  1. Irreversible Inhibition of Human Immunodeficiency Virus Type 1 Integrase by Dicaffeoylquinic Acids†

    PubMed Central

    Zhu, Kai; Cordeiro, Mara L.; Atienza, Jocelyn; Robinson, W. Edward; Chow, Samson A.

    1999-01-01

    Human immunodeficiency virus type 1 (HIV-1) and other retroviruses require integration of a double-stranded DNA copy of the RNA genome into the host cell chromosome for productive infection. The viral enzyme, integrase, catalyzes the integration of retroviral DNA and represents an attractive target for developing antiretroviral agents. We identified several derivatives of dicaffeoylquinic acids (DCQAs) that inhibit HIV-1 replication in tissue culture and catalytic activities of HIV-1 integrase in vitro. The specific step at which DCQAs inhibit the integration in vitro and the mechanism of inhibition were examined in the present study. Titration experiments with different concentrations of HIV-1 integrase or DNA substrate found that the effect of DCQAs was exerted on the enzyme and not the DNA. In addition to HIV-1, DCQAs also inhibited the in vitro activities of MLV integrase and truncated variants of feline immunodeficiency virus integrase, suggesting that these compounds interacted with the central core domain of integrase. The inhibition on retroviral integrases was relatively specific, and DCQAs had no effect on several other DNA-modifying enzymes and phosphoryltransferases. Kinetic analysis and dialysis experiments showed that the inhibition of integrase by DCQAs was irreversible. The inhibition did not require the presence of a divalent cation and was unaffected by preassembling integrase onto viral DNA. The results suggest that the irreversible inhibition by DCQAs on integrase is directed toward conserved amino acid residues in the central core domain during catalysis. PMID:10074185

  2. Thirty years of the human immunodeficiency virus epidemic and beyond

    PubMed Central

    Younai, Fariba S

    2013-01-01

    After more than 30 years of battling a global epidemic, the prospect of eliminating human immunodeficiency virus (HIV) as the most challenging infectious disease of the modern era is within our reach. Major scientific discoveries about the virus responsible for this immunodeficiency disease state, including its pathogenesis, transmission patterns and clinical course, have led to the development of potent antiretroviral drugs that offer great hopes in HIV treatment and prevention. Although these agents and many others still in development and testing are capable of effectively suppressing viral replication and survival, the medical management of HIV infection at the individual and the population levels remains challenging. Timely initiation of antiretroviral drugs, adherence to the appropriate therapeutic regimens, effective use of these agents in the pre and post-exposure prophylaxis contexts, treatment of comorbid conditions and addressing social and psychological factors involved in the care of individuals continue to be important considerations. PMID:24136672

  3. Inhibition of Human Immunodeficiency Virus Replication by Antisense Oligodeoxynucleotides

    NASA Astrophysics Data System (ADS)

    Goodchild, John; Agrawal, Sudhir; Civeira, Maria P.; Sarin, Prem S.; Sun, Daisy; Zamecnik, Paul C.

    1988-08-01

    Twenty different target sites within human immunodeficiency virus (HIV) RNA were selected for studies of inhibition of HIV replication by antisense oligonucleotides. Target sites were selected based on their potential capacity to block recognition functions during viral replication. Antisense oligomers complementary to sites within or near the sequence repeated at the ends of retrovirus RNA (R region) and to certain splice sites were most effective. The effect of antisense oligomer length on inhibiting virus replication was also investigated, and preliminary toxicity studies in mice show that these compounds are toxic only at high levels. The results indicate potential usefulness for these oligomers in the treatment of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex either alone or in combination with other drugs.

  4. A new subtype of human immunodeficiency virus type 1 (MVP-5180) from Cameroon.

    PubMed Central

    Gürtler, L G; Hauser, P H; Eberle, J; von Brunn, A; Knapp, S; Zekeng, L; Tsague, J M; Kaptue, L

    1994-01-01

    A new subtype (MVP-5180) of human immunodeficiency virus type 1 (HIV-1) was isolated from a Cameroonian AIDS patient. MVP-5180 was grown in several human T-cell lines and the monocytic U937 line. MVP-5180 DNA could not be amplified by nested primer PCR with conventional env primers and could be only very faintly amplified with gag and pol primers. Most German, Ivoirian, and Malawian anti-HIV-1 sera reacted faintly or moderately with Env proteins in an MVP-5180 immunoblot, whereas some Cameroonian sera reacted strongly. Of HIV-1-infected Cameroonians, 8% were identified by serological methods as infected with MVP-5180; 7% were positive when MVP-5180-specific PCR env primers were used. DNA sequence analysis of MVP-5180 showed that its genetic organization was that of HIV-1, with 65% similarity to HIV-1 and 56% similarity to HIV-2 consensus sequences. The env gene of MVP-5180 had similarities to HIV-1 and HIV-2 of 53 and of 49%, respectively. V3 loop analysis identified a crown of Gly-Pro-Met-Arg by using cloned DNA and Gly-Pro-Leu-Arg by using PCR-amplified DNA, neither of which configuration has been described for other HIV strains. In an analysis of relationships, MVP-5180 occupied a position distant to all other HIV-1 strains, including the chimpanzee simian immunodeficiency virus type 1 SIVcpz and the Uganda virus U455, and closer to the HIV-1/HIV-2 divergence node. MVP-5180, together with another Cameroonian isolate, ANT-70, constitutes a group subtype O of the most divergent HIV-1 isolates yet identified. Characterization of MVP-5180 is important for understanding the natural history of the primate immunodeficiency viruses and for the development of vaccines and diagnostics. PMID:8107219

  5. Molecular biology of the human immunodeficiency virus type 1

    SciTech Connect

    Haseltine, W.A. )

    1991-07-01

    The immunodeficiency virus type 1 ia a complex retrovirus. In addition to genes that specify the proteins of the virus particle and the replicative enzymes common to all retroviruses, HIV-1 specifies at least six additional proteins that regulate the virus cycle. Two of these regulatory genes, tat and rev, specify proteins essential for replication. These proteins bind to specific sequences of newly synthesized virus RNA and profoundly affect virus protein expression. Tat and rev appear to be prototypes of novel eukaryotic regulatory proteins. These two genes may play a central role in regulating the rate of virus replication. Three other viral genes, vif, vpu, and vpr, affect the assembly and replication capacity of newly made virus particles. These genes may play a critical role in spread of the virus from tissue to tissue and from person to person. Our understanding of the contribution of each of the virus structural proteins and regulatory genes to the complex life cycle of the virus in natural infections is incomplete. However, enough insight has been gained into the structure and function of each of these components to provide a firm basis for rational antiviral drug development.

  6. Antiretroviral therapy reduces neurodegeneration in human immunodeficiency virus infection

    PubMed Central

    Bryant, Alex K.; Ellis, Ronald J.; Umlauf, Anya; Gouaux, Ben; Soontornniyomkij, Virawudh; Letendre, Scott L.; Achim, Cristian L.; Masliah, Eliezer; Grant, Igor; Moore, David J.

    2015-01-01

    Objective To determine the effect of virally-suppressive antiretroviral therapy on cortical neurodegeneration and associated neurocognitive impairment. Design Retrospective, postmortem observational study. Methods Clinical neuropsychological and postmortem neuropathology data were analyzed in 90 human immunodeficiency virus-infected volunteers from the general community who had never undergone antiretroviral therapy (n=7, “naïve”) or who had undergone antiretroviral therapy and whose plasma viral load was detectable (n = 64 “unsuppressed”) or undetectable (n = 19, “suppressed”) at the last clinical visit prior to death. Subjects were predominately male (74/90, 82%) with a mean age of 44.7 years (SD 9.8). Cortical neurodegeneration was quantified by measuring microtubule-associated protein (MAP2) and synaptophysin (SYP) density in midfrontal cortex tissue sections. Results The suppressed group had higher SYP density than the naïve group (p = 0.007) and higher MAP2 density than the unsuppressed group (p = 0.04). The suppressed group had lower odds of human immunodeficiency virus-associated neurocognitive disorders than naïve (OR 0.07, p = 0.03). Higher SYP was associated with lower likelihood of human immunodeficiency virus-associated neurocognitive disorders in univariable (OR 0.8, p=0.03) and multivariable models after controlling for antiretroviral treatment and brain human immunodeficiency virus p24 protein levels (OR 0.72, p=0.01). Conclusions We conclude that virally suppressive antiretroviral treatment protects against cortical neurodegeneration. Further, we find evidence supporting the causal chain from treatment-mediated peripheral and central nervous system viral load suppression to reduced neurodegeneration and improved neurocognitive outcomes. PMID:25686681

  7. Pathogenesis of experimentally induced feline immunodeficiency virus infection in cats.

    PubMed

    Yamamoto, J K; Sparger, E; Ho, E W; Andersen, P R; O'Connor, T P; Mandell, C P; Lowenstine, L; Munn, R; Pedersen, N C

    1988-08-01

    Feline immunodeficiency virus (FIV; formerly, feline T-lymphotropic lentivirus) is a typical lentivirus resembling human and simian immunodeficiency viruses in morphologic features, protein structure, and reverse transcriptase enzyme. It is antigenically dissimilar, however. The virus is tropic for primary and permanent feline T-lymphoblastoid cells and Crandell feline kidney cells. The virus did not grow in other permanent feline non-lymphoblastoid cells that were tested, or in lymphoid and non-lymphoid cells from man, dogs, mice, and sheep. During short-term inoculation studies in cats, the feline immunodeficiency-like syndrome found in nature was not experimentally induced, but a distinct primary phase of infection was observed. Fever and neutropenia were observed 4 to 5 weeks after inoculation; fever lasted several days, and neutropenia persisted from 1 to 9 weeks. Generalized lymphadenopathy that persisted for 2 to 9 months appeared at the same time. Antibodies to FIV appeared 2 weeks after inoculation and then plateaued. Virus was reisolated from the blood of all infected cats within 4 to 5 weeks after inoculation and persisted indefinitely in the face of humoral antibody response. Virus was recovered from blood, plasma, CSF and saliva, but not from colostrum or milk. Contact transmission was achieved slowly in one colony of naturally infected cats, but not between experimentally infected and susceptible specific-pathogen-free cats kept together for periods as long as 4 to 14 months. The infection was transmitted readily, however, by parenteral inoculation with blood, plasma, or infective cell culture fluids. In utero and lactogenic transmission were not observed in kittens born to naturally or experimentally infected queens. Lymphadenopathy observed during the initial stage of FIV infection was ascribed to lymphoid hyperplasia and follicular dysplasia. A myeloproliferative disorder was observed in 1 cat with experimentally induced infection. PMID:2459996

  8. Human immunodeficiency virus prevention with youth.

    PubMed

    McBride, Dominica F; Bell, Carl C

    2011-03-01

    For years, the HIV pandemic was seemingly mysterious and uncontrollable. However, it is now known that with technology, this virus can be stopped from becoming fatal, and with prevention further infection can be stopped. With the application of certain principles and knowledge, this pandemic can be turned into something much less nocuous and pervasive. Various researchers and programs have effectively demonstrated this reality, showing the possibilities of ameliorating the propagation of this virus through prevention. This article reviews the risk and protective factors associated with HIV-related behaviors and describes various effective prevention programs.

  9. The Human Immunodeficiency Virus: Infectivity and Mechanisms of Pathogenesis

    NASA Astrophysics Data System (ADS)

    Fauci, Anthony S.

    1988-02-01

    Infection with the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus (the CD4 molecule). HIV also has tropism for the brain leading to neuropsychiatric abnormalities. Besides inducing cell death, HIV can interfere with T4 cell function by various mechanisms. The monocyte serves as a reservoir for HIV and is relatively refractory to its cytopathic effects. HIV can exist in a latent or chronic form which can be converted to a productive infection by a variety of inductive signals.

  10. Brazilian response to the human immunodeficiency virus/acquired immunodeficiency syndrome epidemic among injection drug users.

    PubMed

    Mesquita, Fábio; Doneda, Denise; Gandolfi, Denise; Nemes, Maria Inês Battistella; Andrade, Tarcísio; Bueno, Regina; Piconez e Trigueiros, Daniela

    2003-12-15

    The Brazilian response to the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic is being observed all over the world because of its success. Understanding the role of injection drug users (IDUs) in the epidemic and the political response thereto is a key factor in the control of the epidemic in Brazil. This paper summarizes some of the most important analyses of the Brazilian response to the HIV/AIDS epidemic among and from IDUs. Key elements of the response include the support of the Brazilian Universal Public Health System, the provision of universal access to highly active antiretroviral therapy, and the creation of harm reduction projects that are politically and financially supported by the federal government. The response among and from IDUs is a key element in overall control of the HIV/AIDS epidemic. The response to the epidemic among and from IDUs has been headed in the correct direction since its beginning and is now being intensively expanded.

  11. ACOG Committee Opinion No. 536: Human immunodeficiency virus and acquired immunodeficiency syndrome and women of color.

    PubMed

    2012-09-01

    In the United States, most new cases of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) occur among women of color (primarily African American and Hispanic women). Most women of color acquire the disease from heterosexual contact, often from a partner who has undisclosed risk factors for HIV infection. Safe sex practices, especially consistent condom use, must be emphasized for all women, including women of color. A combination of testing, education, and brief behavioral interventions can help reduce the rate of HIV infection and its complications among women of color. In addition,biomedical interventions such as early treatment of patients infected with HIV and pre-exposure antiretroviral prophylaxis of high-risk individuals offer promise for future reductions in infections.

  12. Absence of Active Hepatitis C Virus Infection in Human Immunodeficiency Virus Clinics in Zambia and Mozambique

    PubMed Central

    Wandeler, Gilles; Mulenga, Lloyd; Hobbins, Michael; Joao, Candido; Sinkala, Edford; Hector, Jonas; Aly, Musa; Chi, Benjamin H.; Egger, Matthias; Vinikoor, Michael J.

    2016-01-01

    Few studies have evaluated the prevalence of replicating hepatitis C virus (HCV) infection in sub-Saharan Africa. Among 1812 individuals infected with human immunodeficiency virus, no patient in rural Mozambique and 4 patients in urban Zambia were positive for anti-HCV antibodies. Of these, none had confirmed HCV replication. PMID:27047986

  13. Tissue tropism of simian immunodeficiency virus in rhesus monkeys

    SciTech Connect

    Wyand, M.S.

    1989-01-01

    Simian immunodeficiency virus (SIV) is a T-lymphotropic lentivirus that is genetically, immunologically, and morphologically related to the human immunodeficiency viruses type 1 and 2 (HIV-1, HIV-2). In rhesus monkeys, SIV induces a progressively fatal immunodeficiency syndrome strikingly similar to human acquired immunodeficiency syndrome (AIDS). The tissue and cellular tropism of SIV was determined by immunocytochemistry and in situ hybridization using a 3.48 kilobase SIV envelope gene probe labeled with biotin, {sup 35}S, or {sup 3}H. Probes labeled with {sup 35}S nonspecifically bound to tissue eosinophils and produced poor signal resolution compared to tritium labeled probes. Biotin labeled probes did not detect SIV under similar hybridization conditions. Formalin-fixed, paraffin-embedded tissues produced strong hybridization signal with superior morphology compared to frozen tissues. Gastrointestinal, respiratory, and lymphoid tissues most frequently contained SIV RNA. The distribution of SIV did not correlate with sex, or viral inoculum, but was most extensive in animals with SIV induced granulomatous encephalitis. SIV was most frequently observed in lymphocytes and macrophages. In the brain focal granulomas were composed almost entirely of EBM11+, lysozyme+, macrophages which contained large amounts of SIV RNA and p27 core protein detected by the monoclonal antibody R1C7. Cells away from granulomas in the brain parenchyma and around blood vessels contained virus and were compatible with oligodendrocytes and astrocytes. Lymph nodes in follicular hyperplasia contained small numbers of SIV positive cells compatible with lymphocytes in the paracortex and mantle zones as well as in cells of the germinal center. Lymph nodes in various stages of follicular depletion with expanded paracortices contained large numbers of cells with SIV RNA in lymphocytes and macrophages.

  14. Nonnucleoside reverse transcriptase inhibitors that potently and specifically block human immunodeficiency virus type 1 replication.

    PubMed Central

    Romero, D L; Busso, M; Tan, C K; Reusser, F; Palmer, J R; Poppe, S M; Aristoff, P A; Downey, K M; So, A G; Resnick, L

    1991-01-01

    Certain bis(heteroaryl)piperazines (BHAPs) are potent inhibitors of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) at concentrations lower by 2-4 orders of magnitude than that which inhibits normal cellular DNA polymerase activity. Combination of a BHAP with nucleoside analog HIV-1 RT inhibitors suggested that together these compounds inhibited RT synergistically. In three human lymphocytic cell systems using several laboratory and clinical HIV-1 isolates, the BHAPs blocked HIV-1 replication with potencies nearly identical to those of 3'-azido-2',3'-dideoxythymidine or 2',3'-dideoxyadenosine; in primary cultures of human peripheral blood mononuclear cells, concentrations of these antiviral agents were lower by at least 3-4 orders of magnitude than cytotoxic levels. The BHAPs do not inhibit replication of HIV-2, the simian or feline immunodeficiency virus, or Rauscher murine leukemia virus in culture. Evaluation of a BHAP in HIV-1-infected SCID-hu mice (severe combined immunodeficient mice implanted with human fetal lymph node) showed that the compound could block HIV-1 replication in vivo. The BHAPs are readily obtained synthetically and have been extensively characterized in preclinical evaluations. These compounds hold promise for the treatment of HIV-1 infection. Images PMID:1717988

  15. Limited Protection from a Pathogenic Chimeric Simian-Human Immunodeficiency Virus Challenge following Immunization with Attenuated Simian Immunodeficiency Virus

    PubMed Central

    Lewis, Mark G.; Yalley-Ogunro, Jake; Greenhouse, Jack J.; Brennan, Terry P.; Jiang, Jennifer Bo; VanCott, Thomas C.; Lu, Yichen; Eddy, Gerald A.; Birx, Deborah L.

    1999-01-01

    Two live attenuated single-deletion mutant simian immunodeficiency virus (SIV) constructs, SIV239Δnef and SIVPBj6.6Δnef, were tested for their abilities to stimulate protective immunity in macaques. During the immunization period the animals were examined for specific immune responses and virus growth. Each construct generated high levels of specific immunity in all of the immunized animals. The SIV239Δnef construct was found to grow to high levels in all immunized animals, with some animals remaining positive for virus isolation and plasma RNA throughout the immunization period. The SIVPBj6.6Δnef was effectively controlled by all of the immunized animals, with virus mostly isolated only during the first few months following immunization and plasma RNA never detected. Following an extended period of immunization of over 80 weeks, the animals were challenged with a pathogenic simian-human immunodeficiency virus (SHIV) isolate, SIV89.6PD, by intravenous injection. All of the SIV239Δnef-immunized animals became infected with the SHIV isolate; two of five animals eventually controlled the challenge and three of five animals, which failed to check the immunizing virus, progressed to disease state before the unvaccinated controls. One of five animals immunized with SIVPBj6.6Δnef totally resisted infection by the challenge virus, while three others limited its growth and the remaining animal became persistently infected and eventually died of a pulmonary thrombus. These data indicate that vaccination with attenuated SIV can protect macaques from disease and in some cases from infection by a divergent SHIV. However, if animals are unable to control the immunizing virus, potential damage that can accelerate the disease course of a pathogenic challenge virus may occur. PMID:9882330

  16. NMR Structure of the Myristylated Feline Immunodeficiency Virus Matrix Protein

    PubMed Central

    Brown, Lola A.; Cox, Cassiah; Baptiste, Janae; Summers, Holly; Button, Ryan; Bahlow, Kennedy; Spurrier, Vaughn; Kyser, Jenna; Luttge, Benjamin G.; Kuo, Lillian; Freed, Eric O.; Summers, Michael F.

    2015-01-01

    Membrane targeting by the Gag proteins of the human immunodeficiency viruses (HIV types-1 and -2) is mediated by Gag’s N-terminally myristylated matrix (MA) domain and is dependent on cellular phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. To determine if other lentiviruses employ a similar membrane targeting mechanism, we initiated studies of the feline immunodeficiency virus (FIV), a widespread feline pathogen with potential utility for development of human therapeutics. Bacterial co-translational myristylation was facilitated by mutation of two amino acids near the amino-terminus of the protein (Q5A/G6S; myrMAQ5A/G6S). These substitutions did not affect virus assembly or release from transfected cells. NMR studies revealed that the myristyl group is buried within a hydrophobic pocket in a manner that is structurally similar to that observed for the myristylated HIV-1 protein. Comparisons with a recent crystal structure of the unmyristylated FIV protein [myr(-)MA] indicate that only small changes in helix orientation are required to accommodate the sequestered myr group. Depletion of PI(4,5)P2 from the plasma membrane of FIV-infected CRFK cells inhibited production of FIV particles, indicating that, like HIV, FIV hijacks the PI(4,5)P2 cellular signaling system to direct intracellular Gag trafficking during virus assembly. PMID:25941825

  17. Inflammatory joint disease and human immunodeficiency virus infection

    PubMed Central

    Forster, S M; Seifert, M H; Keat, A C; Rowe, I F; Thomas, B J; Taylor-Robinson, D; Pinching, A J; Harris, J R W

    1988-01-01

    Nine men positive for antibody to human immunodeficiency virus (HIV) who developed peripheral, non-erosive arthritis were followed up. The clinical features were compatible with reactive arthritis but were atypical in several respects: the joint symptoms were generally severe, persistent, and unresponsive to non-steroidal anti-inflammatory drugs. The onset of arthritis was associated with various infections, none of which are known to be associated with the development of reactive arthritis. HLA typing was performed for three patients, all of whom were positive for HLA-B27. HIV was isolated from the synovial fluid of one patient. No patient had AIDS before developing arthritis, but four progressed to having AIDS after a mean of 7·5 months, and two died. Arthritis resolved in only one patient. The possibility of HIV infection should be considered in all patients with conditions suggesting reactive arthritis. Synovitis in patients with severe immunodeficiency has important pathogenetic implications. PMID:3135044

  18. Idiopathic genital ulcers in women infected with human immunodeficiency virus.

    PubMed

    Anderson, J; Clark, R A; Watts, D H; Till, M; Arrastia, C; Schuman, P; Cohn, S E; Young, M; Bessen, L; Greenblatt, R; Vogler, M; Swindells, S; Boyer, P

    1996-12-01

    A national survey of investigators caring for human immunodeficiency virus (HIV)-infected women was undertaken to describe the clinical presentation of idiopathic genital ulcer disease. Patients with negative syphilis and herpes simplex testing and/or negative genital ulcer biopsy were included in this study. Study participants (n = 29) were generally severely immunocompromised (median CD4 cell count was 50/mm3, and 68% had an acquired immunodeficiency syndrome [AIDS]-defining opportunistic process). Thirty-seven percent had coexistent oral ulcers and 19% had their genital ulcer progress to fistula formation (four rectovaginal and one vaginal-perineal). There was generally a favorable response to topical, systemic, and intralesional steroid treatment. This study suggests that idiopathic or probable aphthous genital ulcers in women have similar clinical characteristics to aphthous oroesophageal ulcers. Although infrequent, these genital ulcers can cause severe morbidity. Further research is warranted to better define the pathophysiology and optimal management.

  19. Rapid Tests and the Diagnosis of Visceral Leishmaniasis and Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Coinfection.

    PubMed

    Barbosa Júnior, Walter Lins; Ramos de Araújo, Paulo Sérgio; Dias de Andrade, Luiz; Aguiar Dos Santos, Ana Maria; Lopes da Silva, Maria Almerice; Dantas-Torres, Filipe; Medeiros, Zulma

    2015-11-01

    After the emergence of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), the number of visceral leishmaniasis (VL)-HIV/AIDS coinfections has increased worldwide. Herein, we assessed the usefulness of an rK39-based immunochromatographic test (rK39 ICT) (DiaMed-IT LEISH(®); DiaMed AG, Cressier-sur-Morat, Switzerland) and a latex agglutination test (KAtex; Kalon Biological, Guildford, United Kingdom) for urinary antigen detection to diagnose VL in 15 HIV/AIDS patients from northeastern Brazil. VL diagnosis was based on clinical findings, cytology, serology, parasite DNA, and/or urinary antigen detection. VL was confirmed in seven out of 15 HIV/AIDS patients. Only three patients were positive in bone marrow cytology, three patients were conventional polymerase chain reaction (PCR) positive, while six were real-time PCR positive. All patients were direct agglutination test (DAT) (Royal Tropical Institute, Amsterdam, The Netherlands) positive; of these, four were positive by rK39 ICT and five by KAtex. Large-scale studies are needed to validate the use of the KAtex in the national public health laboratory network in Brazil, aiming at improving the diagnosis of VL in HIV/AIDS patients in this country.

  20. Rapid Tests and the Diagnosis of Visceral Leishmaniasis and Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Coinfection.

    PubMed

    Barbosa Júnior, Walter Lins; Ramos de Araújo, Paulo Sérgio; Dias de Andrade, Luiz; Aguiar Dos Santos, Ana Maria; Lopes da Silva, Maria Almerice; Dantas-Torres, Filipe; Medeiros, Zulma

    2015-11-01

    After the emergence of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), the number of visceral leishmaniasis (VL)-HIV/AIDS coinfections has increased worldwide. Herein, we assessed the usefulness of an rK39-based immunochromatographic test (rK39 ICT) (DiaMed-IT LEISH(®); DiaMed AG, Cressier-sur-Morat, Switzerland) and a latex agglutination test (KAtex; Kalon Biological, Guildford, United Kingdom) for urinary antigen detection to diagnose VL in 15 HIV/AIDS patients from northeastern Brazil. VL diagnosis was based on clinical findings, cytology, serology, parasite DNA, and/or urinary antigen detection. VL was confirmed in seven out of 15 HIV/AIDS patients. Only three patients were positive in bone marrow cytology, three patients were conventional polymerase chain reaction (PCR) positive, while six were real-time PCR positive. All patients were direct agglutination test (DAT) (Royal Tropical Institute, Amsterdam, The Netherlands) positive; of these, four were positive by rK39 ICT and five by KAtex. Large-scale studies are needed to validate the use of the KAtex in the national public health laboratory network in Brazil, aiming at improving the diagnosis of VL in HIV/AIDS patients in this country. PMID:26416105

  1. Recombinant virus assay: a rapid, phenotypic assay for assessment of drug susceptibility of human immunodeficiency virus type 1 isolates.

    PubMed Central

    Kellam, P; Larder, B A

    1994-01-01

    Antiviral drug susceptibility assays for clinical human immunodeficiency virus type 1 (HIV-1) isolates are required to monitor the development of drug resistance during clinical trials and antiretroviral drug therapy. First-generation phenotypic assays possess a number of drawbacks, not least the selection of unrepresentative virus populations during cocultivation. Here we describe a rapid phenotypic assay for the assessment of the susceptibility of clinical isolates to reverse transcriptase (RT) inhibitors. This procedure, called the recombinant virus assay, allows the generation of viable virus by homologous recombination of a PCR-derived pool of RT coding sequences into an RT-deleted, noninfectious proviral clone, pHIV delta BstEII. A nested PCR procedure has been optimized to allow the amplification of an RT pool from both uncultured and cocultured infected patient peripheral blood lymphocyte (PBL) DNA for subsequent use in the creation of recombinant viruses. Analysis of two patients during the course of zidovudine therapy showed that this approach produced viruses which accurately exhibited the same genotype and phenotype as that of the original infected PBL DNA. The recombinant virus assay can be performed in approximately 3 weeks without the use of donor PBLs and therefore represents a rapid, nonselective procedure for the assay of clinical isolates. Images PMID:8141575

  2. Post-translational intracellular trafficking determines the type of immune response elicited by DNA vaccines expressing Gag antigen of Human Immunodeficiency Virus Type 1 (HIV-1)

    PubMed Central

    Wallace, Aaron; West, Kim; Rothman, Alan L; Ennis, Francis A; Lu, Shan; Wang, Shixia

    2013-01-01

    In the current study, immune responses induced by Gag DNA vaccines with different designs were evaluated in Balb/C mice. The results demonstrated that the DNA vaccine with the full length wild type gag gene (Wt-Gag) mainly produced Gag antigens intracellularly and induced a higher level of cell-mediated immune (CMI) responses, as measured by IFN-gamma ELISPOT, intracellular cytokine staining (ICS), and cytotoxic T lymphocytes (CTL) assays against a dominant CD8+ T cell epitope (AMQMLKETI). In contrast, the addition of a tissue plasminogen activator (tPA) leader sequence significantly improved overall Gag protein expression/secretion and Gag-specific antibody responses; however, Gag-specific CMI responses were decreased. The mutation of zinc-finger motif changed Gag protein expression patterns and reduced the ability to generate both CMI and antibody responses against Gag. These findings indicate that the structure and post-translational processing of antigens expressed by DNA vaccines play a critical role in eliciting optimal antibody or CMI responses. PMID:23941868

  3. Immune suppression in calves with bovine immunodeficiency virus.

    PubMed Central

    Zhang, S; Wood, C; Xue, W; Krukenberg, S M; Chen, Q; Minocha, H C

    1997-01-01

    The present study was designed to evaluate the effect of bovine immunodeficiency virus (BIV) infection on immune functions and possible interactions between BIV and other bovine viruses in calves. Ten calves were inoculated intravenously with BIV, and five served as controls. An increased lymphocyte proliferation to BIV gag protein was demonstrated 2 to 6 weeks after BIV inoculation (P < 0.05). Lymphocyte subset differentiation revealed a decreased CD4/CD8 ratio (P < 0.05) during weeks 2 to 7, suggesting a possible immune dysfunction in BIV-infected calves. When the calves were inoculated with bovine herpesvirus type 1 (BHV-1), the antibody response to BHV-1 in BIV-infected calves was delayed and the antibody titers were significantly lower (P < 0.05). Injection of bovine viral diarrhea virus vaccine also elicited a lower neutralizing antibody response in BIV-infected calves. The results indicated that immune suppression occurred in BIV-infected calves. PMID:9067663

  4. Inactivation of human immunodeficiency virus type 1 by alcohols.

    PubMed

    van Bueren, J; Larkin, D P; Simpson, R A

    1994-10-01

    Alcohols are commonly used as disinfectants for skin, surfaces and immersion of some medical instruments. Measurements of the activity of alcohols against human immunodeficiency virus type 1 (HIV-1) must take account of the compatibility of neutralizers used to stop the disinfectant reaction, and of toxicity to the cell line used to detect residual virus. We have developed protocols to measure the efficacy of alcohols against HIV in suspension and dried onto surfaces in the presence of high and low protein concentrations. High titres of HIV in suspension were rapidly inactivated by 70% ethanol, independent of the protein load. When virus was dried onto a glass surface, the rate of inactivation decreased when high levels of protein were present. Due to its rapid evaporation, a spray or a wipe with alcohol cannot be guaranteed to disinfect a surface contaminated with blood or other body fluids without preliminary cleaning.

  5. Interference to human immunodeficiency virus type 1 infection in the absence of downmodulation of the principal virus receptor, CD4.

    PubMed Central

    Volsky, D J; Simm, M; Shahabuddin, M; Li, G; Chao, W; Potash, M J

    1996-01-01

    It is thought that interference during human immunodeficiency virus type 1 (HIV-1) infection is established by downmodulation of the principal virus receptor, CD4. Here we present evidence to the contrary. At various times after primary infection, we superinfected T cells in vitro by exposure to a genetically distinct viral clone or to a virus carrying the chloramphenicol acetyltransferase gene. Replication of each virus strain was determined by restriction enzyme analysis of total cellular DNA, by PCR amplification of viral DNA, or by assay of cell extracts for chloramphenicol acetyltransferase activity. We found that efficient viral interference is established within 24 h of infection at a multiplicity of infection of 1. At that time, expression of viral structural proteins was low and infected cells displayed undiminished levels of surface CD4 and were fully susceptible to virus binding and fusion. Superinfection by either cell-free HIV-1 or cocultivation was blocked. Cells resistant to superinfection by HIV-1 remained susceptible to Moloney murine leukemia and vaccinia viruses. No interference was observed 4 h after primary infection or in cells infected with either UV-inactivated HIV-1 or a mutant virus defective in virus-cell fusion activity, indicating that binding of primary virus to CD4 is insufficient to prevent superinfection. The minimum viral requirements for this interference are that HIV-1 must be able to enter cells and synthesize viral DNA; Tat-mediated transcription is dispensable. Our results support the existence of a novel pathway to interference to HIV-1 infection, which we term postentry interference, which blocks superinfection during intracellular phases of the virus life cycle. PMID:8648718

  6. Seroprevalence of bovine immunodeficiency virus and bovine leukemia virus in draught animals in Cambodia.

    PubMed

    Meas, S; Ohashi, K; Tum, S; Chhin, M; Te, K; Miura, K; Sugimoto, C; Onuma, M

    2000-07-01

    Since bovine immunodeficiency virus (BIV), known as bovine lentivirus, has been detected in dairy and beef cattle in various countries around the world, a prevalence study of antibodies to BIV and bovine leukemia virus (BLV) was conducted in draught animals in five provinces in Cambodia, where protozoan parasite infections were suspected in some animals. To clarify the status of draught animals including Haryana, Brahman, mixed-breed, local breed cattle and muscle water buffaloes, a total of 544 cattle and 42 buffaloes were tested, and 26.3 and 16.7%, respectively, were found positive for anti-BIV p26 antibodies determined by Western blotting. There were 5.3% positive for anti-BLV antibodies detected by immunodiffusion test among the cattle, but no reactors among buffaloes and no dual infection for both BIV and BLV was determined in this study. Peripheral blood mononuclear cells from BIV-seropositive cattle were found to have BIV-provirus DNA, as detected by polymerase chain reaction and subsequent Southern blot hybridization. This is the first evidence for the presence of BIV and BLV infections in draught animals in tropical countries such as Cambodia. This wide distribution of BIV suggests its association with problems in animal health as reported worldwide, and that a primary BIV infection can predispose death of affected animals by other aggressive pathogens or stresses.

  7. Plasmoblastic lymphoma associated with human immunodeficiency virus.

    PubMed

    Horváth, Emoke; Krenács, L; Bagdi, Eniko; Pávai, Z; Macarie, I; Nagy, Elod-Erno; Demian, Smaranda

    2008-01-01

    Plasmoblastic lymphoma (PBL) is a subtype of the diffuse large B-cell lymphoma, typically present as extranodal disease associated with human immune deficiency virus (HIV) infection. PBLs are often the initial manifestation of AIDS. Here we present a case of PBL concerning the oral cavity. A 34-year-old woman presented a tumor in the oral cavity that involved the maxilla and gingiva (confirmed by CT-scan). The gingival biopsy showed a massive infiltration by large lymphoid cells with round, vesicular nuclei, prominent nucleoli, fine chromatin and an significant amount of basophilic cytoplasm which express CD79a, CD138, cytoplasmic lambda light chain and LCA, without staining for CD20, CD38, CD3 and CTK. Serological analysis confirmed HIV positivity. PBLs lack most B-lineage markers, but many express CD79a in at least some of the cells, therefore generate difficulties in differential diagnosis. Overall assessment and correlation of the histopathological and immunohistochemical features with the clinical findings and serology investigation are the most helpful diagnostic tools and can lead to the final diagnosis.

  8. Plasmoblastic lymphoma associated with human immunodeficiency virus.

    PubMed

    Horváth, Emoke; Krenács, L; Bagdi, Eniko; Pávai, Z; Macarie, I; Nagy, Elod-Erno; Demian, Smaranda

    2008-01-01

    Plasmoblastic lymphoma (PBL) is a subtype of the diffuse large B-cell lymphoma, typically present as extranodal disease associated with human immune deficiency virus (HIV) infection. PBLs are often the initial manifestation of AIDS. Here we present a case of PBL concerning the oral cavity. A 34-year-old woman presented a tumor in the oral cavity that involved the maxilla and gingiva (confirmed by CT-scan). The gingival biopsy showed a massive infiltration by large lymphoid cells with round, vesicular nuclei, prominent nucleoli, fine chromatin and an significant amount of basophilic cytoplasm which express CD79a, CD138, cytoplasmic lambda light chain and LCA, without staining for CD20, CD38, CD3 and CTK. Serological analysis confirmed HIV positivity. PBLs lack most B-lineage markers, but many express CD79a in at least some of the cells, therefore generate difficulties in differential diagnosis. Overall assessment and correlation of the histopathological and immunohistochemical features with the clinical findings and serology investigation are the most helpful diagnostic tools and can lead to the final diagnosis. PMID:18758634

  9. Enteric ganglionitis in rhesus macaques infected with simian immunodeficiency virus.

    PubMed

    Orandle, Marlene S; Veazey, Ronald S; Lackner, Andrew A

    2007-06-01

    Gastrointestinal (GI) disease is a debilitating feature of human immunodeficiency virus (HIV) infection that can occur in the absence of histopathological abnormalities or identifiable enteropathogens. However, the mechanisms of GI dysfunction are poorly understood. The present study was undertaken to characterize changes in resident and inflammatory cells in the enteric nervous system (ENS) of macaques during the acute stage of simian immunodeficiency virus (SIV) infection to gain insight into potential pathogenic mechanisms of GI disease. Ganglia from duodenum, ileum, and colon were examined in healthy and acutely infected macaques by using a combination of routine histology, double-label immunofluorescence and in situ hybridization. Evaluation of tissues from infected macaques showed progressive infiltration of myenteric ganglia by CD3+ T cells and IBA1+ macrophages beginning as early as 8 days postinfection. Quantitative image analysis revealed that the severity of myenteric ganglionitis increased with time after SIV infection and, in general, was more severe in ganglia from the small intestine than in ganglia from the colon. Despite an abundance of inflammatory cells in myenteric ganglia during acute infection, the ENS was not a target for virus infection. This study provides evidence that the ENS may be playing a role in the pathogenesis of GI disease and enteropathy in HIV-infected people.

  10. Lymphatic Dissemination of Simian Immunodeficiency Virus after Penile Inoculation

    PubMed Central

    Ma, Zhong-Min; Dutra, Joseph; Fritts, Linda

    2016-01-01

    ABSTRACT The human immunodeficiency virus (HIV) is primarily transmitted by heterosexual contact, and approximately equal numbers of men and women worldwide are infected with the virus. Understanding the biology of HIV acquisition and dissemination in men exposed to the virus by insertive penile intercourse is likely to help with the rational design of vaccines that can limit or prevent HIV transmission. To characterize the target cells and dissemination pathways involved in establishing systemic simian immunodeficiency virus (SIV) infection, we necropsied male rhesus macaques at 1, 3, 7, and 14 days after penile SIV inoculation and quantified the levels of unspliced SIV RNA and spliced SIV RNA in tissue lysates and the number of SIV RNA-positive cells in tissue sections. We found that penile (glans, foreskin, coronal sulcus) T cells and, to a lesser extent, macrophages and dendritic cells are primary targets of infection and that SIV rapidly reaches the regional lymph nodes. At 7 days after inoculation, SIV had disseminated to the blood, systemic lymph nodes, and mucosal lymphoid tissues. Further, at 7 days postinoculation (p.i.), spliced SIV RNA levels were the highest in the genital lymph nodes, indicating that this is the site where the infection is initially amplified. By 14 days p.i., spliced SIV RNA levels were high in all tissues, but they were the highest in the gastrointestinal tract, indicating that the primary site of virus replication had shifted from the genital lymph nodes to the gut. The stepwise pattern of virus replication and dissemination described here suggests that vaccine-elicited immune responses in the genital lymph nodes could help prevent infection after penile SIV challenge. IMPORTANCE To be the most effective, vaccines should produce antiviral immune responses in the anatomic sites of virus replication. Thus, understanding the path taken by HIV from the mucosal surfaces, which are the site of virus exposure, to the deeper tissues where

  11. Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia.

    PubMed

    Churchill, Melissa J; Wesselingh, Steven L; Cowley, Daniel; Pardo, Carlos A; McArthur, Justin C; Brew, Bruce J; Gorry, Paul R

    2009-08-01

    Astrocyte infection with human immunodeficiency virus (HIV) is considered rare, so astrocytes are thought to play a secondary role in HIV neuropathogenesis. By combining double immunohistochemistry, laser capture microdissection, and highly sensitive multiplexed polymerase chain reaction to detect HIV DNA in single astrocytes in vivo, we showed that astrocyte infection is extensive in subjects with HIV-associated dementia, occurring in up to 19% of GFAP+ cells. In addition, astrocyte infection frequency correlated with the severity of neuropathological changes and proximity to perivascular macrophages. Our data indicate that astrocytes can be extensively infected with HIV, and suggest an important role for HIV-infected astrocytes in HIV neuropathogenesis.

  12. Efficient magnesium-dependent human immunodeficiency virus type 1 integrase activity.

    PubMed Central

    Engelman, A; Craigie, R

    1995-01-01

    The integrase protein from human immunodeficiency virus type 1 (HIV-1) has generally been reported to require Mn2+ for efficient in vitro activity. We have reexamined the divalent metal ion requirements of HIV-1 integrase and find that the protein is capable of promoting efficient 3' processing and DNA strand transfer with either Mn2+ or Mg2+. The metal ion preference depended upon the reaction conditions. HIV-1 integrase displayed significantly less nonspecific nuclease activity in reaction mixtures containing Mg2+ than it did under the previously described reaction conditions with mixtures containing Mn2+. PMID:7637039

  13. Inactivation of human immunodeficiency virus (HIV) by ionizing radiation in body fluids and serological evidence

    SciTech Connect

    Bigbee, P.D.; Sarin, P.S.; Humphreys, J.C.; Eubanks, W.G.; Sun, D.; Hocken, D.G.; Thornton, A.; Adams, D.E.; Simic, M.G. )

    1989-11-01

    A method to use ionizing radiation to inactivate HIV (Human Immunodeficiency Virus) in human body fluids was studied in an effort to reduce the risk of accidental infection to forensic science laboratory workers. Experiments conducted indicate that an X-ray absorbed dose of 25 krad was required to completely inactivate HIV. This does not alter forensically important constituents such as enzymes and proteins in body fluids. This method of inactivation of HIV cannot be used on body fluids which will be subjected to deoxyribonucleic acid (DNA) typing.

  14. Neuromyelitis optica in patients with coexisting human immunodeficiency virus infections.

    PubMed

    Feyissa, Anteneh M; Singh, Parbhdeep; Smith, Robert G

    2013-09-01

    Two patients with known human immunodeficiency virus (HIV) infections and receiving antiretroviral treatment developed neuromyelitis optica (Devic's disease). One patient tested positive for serum aquaporin-4 immunoglobulin G antibodies. Both patients were treated with high dose pulsed intravenous methylprednisolone followed by standard sessions of plasma exchange both at the onset attack and during disease relapses. For maintenance therapy, one patient received rituximab infusions and the second patient received mycophenolate mofetil orally. Despite treatment, both patients are currently wheelchair-bound due to severe paraparesis. Neuromyelitis optica can occur in the course of HIV infection and poses an ongoing therapeutic challenge.

  15. The human immunodeficiency virus reduces network capacity: acoustic noise effect

    PubMed Central

    Tomasi, Dardo; Chang, Linda; de Castro Caparelli, Elisabeth; Telang, Frank; Ernst, Thomas

    2008-01-01

    Increased acoustic noise (AN) during working memory (WM) leads to increased brain activation in healthy individuals, and may have greater impact in human immunodeficiency virus (HIV) patients. Compared to controls, HIV subjects showed reduced AN-activation and lower neuronal marker N-acetylaspartate in prefrontal and parietal cortices. Competing use of the WM network between AN and cognitive load showed lower dynamic range of the hemodynamic responses in prefrontal and parietal cortices in HIV patients. These findings suggest reduced reserve capacity of the WM network in HIV patients and additional stress (e.g. AN) might exhaust the impaired network for more demanding tasks. PMID:16437575

  16. Management of dyslipidemia in patients with human immunodeficiency virus.

    PubMed

    Shalit, Peter

    2014-01-01

    Dyslipidemias are more common in the patient population with human immunodeficiency virus (HIV). Combination antiretroviral therapy (ART) has dramatically reduced HIV-associated morbidity and mortality and has transformed HIV disease into a chronic, manageable condition. As a result, non-AIDS-related illnesses, including cardiovascular diseases, are now the leading causes of death in the HIV-infected population. Optimizing fasting lipid parameters plays an important role in reducing cardiovascular risk in this population. This review focuses on the management of dyslipidemia in HIV-infected individuals treated with combination ART.

  17. Antiretroviral Therapy for Prevention of Human Immunodeficiency Virus Infection.

    PubMed

    Kalapila, Aley G; Marrazzo, Jeanne

    2016-07-01

    Human immunodeficiency virus (HIV) infection is considered a chronic medical condition. Several new drugs are available, including fixed-dose combination tablets, that have greatly simplified combination antiretroviral therapy (ART) regimens to treat HIV, while increasing the life-expectancy of infected individuals. In the last decade, multiple well-regarded studies have established the benefits of using ART in high-risk, HIV-negative persons to prevent HIV acquisition. The primary care provider must not only understand commonly encountered issues pertaining to ART, such as toxicities and drug interactions, but also needs to be aware of using ART for HIV prevention. PMID:27235622

  18. Feline immunodeficiency virus reverse transcriptase: expression, functional characterization, and reconstitution of the 66- and 51-kilodalton subunits.

    PubMed Central

    Amacker, M; Hottiger, M; Hübscher, U

    1995-01-01

    The two subunits of the feline immunodeficiency virus (FIV) reverse transcriptase (RT) were cloned and functionally expressed in Escherichia coli. The recombinant proteins are enzymatically active as homodimers (p66 and p51) as well as a heterodimer p66/p51. The biochemical properties of the FIV RT are very similar to those of the counterpart of the human immunodeficiency virus type 1 in being an RNA-dependent and DNA-dependent DNA polymerase. When a double-stranded DNA containing a small gap of 26 nucleotides was tested, we found a new activity of the FIV RT p66/p51 heterodimer--the cat viral enzyme could perform strand displacement DNA synthesis of approximately 300 bases. The FIV RT homodimer p66 alone could carry out limited strand displacement DNA synthesis, but this activity was stimulated by the p51 subunit at a molar ratio of one molecule of p66 to five molecules of p51. On the other hand, the homodimeric p51 itself was unable to fill a small gap of 26 nucleotides in a double-stranded DNA substrate and was not active by itself in strand displacement DNA synthesis. These data are in agreement with an earlier finding of strand displacement DNA synthesis by human immunodeficiency virus type 1 RT (M. Hottiger, V.N. Podust, R.L. Thimmig, C.S. McHenry, and U. Hübscher. J. Biol. Chem. 269:986-991, 1994). Our data therefore suggest a general and important function of lentiviral p51 subunits in strand displacement DNA synthesis which appears to be required in later stages of the lentiviral replication cycle, when DNA-dependent DNA synthesis occurs on double-stranded DNA. PMID:7545246

  19. Substrate inhibition of the human immunodeficiency virus type 1 reverse transcriptase.

    PubMed Central

    Furman, P A; Painter, G; Wilson, J E; Cheng, N; Hopkins, S

    1991-01-01

    Substrate inhibition was observed with the heterodimeric (p66/p51) and the homodimeric (p66/p66, p51/p51) forms of human immunodeficiency virus type 1 reverse transcriptase (RNA-dependent DNA polymerase, EC 2.7.7.49). An apparent Ki value of 195 +/- 37 microM was determined for dTTP using the bacterial cloned and expressed heterodimer. Similar values were obtained with the homodimeric and the virus-encoded enzymes. When poly-(rC).p(dG)10 was used as template-primer, dGTP exhibited substrate inhibition with an apparent Ki value of 189 +/- 32 microM. Substrate inhibition was not observed with dTTP when DNA.DNA template-primers were used. Hill coefficients for substrate binding determined in the presence of saturating concentrations of template-primer were equal to 1.0, suggesting that substrate inhibition of the heterodimer is not the result of an allosteric mechanism involving the p51 subunit. Furthermore, UV crosslinking experiments with [gamma-32P]dTTP showed crosslinking only to the p66 subunit. Substrate inhibition was not as pronounced with other retroviral reverse transcriptases as it was with human immunodeficiency type 1 reverse transcriptase. Images PMID:1712479

  20. Respiratory Syncytial Virus Infections in Infants Affected by Primary Immunodeficiency

    PubMed Central

    Capretti, Maria Grazia; Lazzarotto, Tiziana; Faldella, Giacomo

    2014-01-01

    Primary immunodeficiencies are rare inherited disorders that may lead to frequent and often severe acute respiratory infections. Respiratory syncytial virus (RSV) is one of the most frequent pathogens during early infancy and the infection is more severe in immunocompromised infants than in healthy infants, as a result of impaired T- and B-cell immune response unable to efficaciously neutralize viral replication, with subsequent increased viral shedding and potentially lethal lower respiratory tract infection. Several authors have reported a severe clinical course after RSV infections in infants and children with primary and acquired immunodeficiencies. Environmental prophylaxis is essential in order to reduce the infection during the epidemic season in hospitalized immunocompromised infants. Prophylaxis with palivizumab, a humanized monoclonal antibody against the RSV F protein, is currently recommended in high-risk infants born prematurely, with chronic lung disease or congenital heart disease. Currently however the prophylaxis is not routinely recommended in infants with primary immunodeficiency, although some authors propose the extension of prophylaxis to this high risk population. PMID:25089282

  1. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false In vitro human immunodeficiency virus (HIV) drug... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid...

  2. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false In vitro human immunodeficiency virus (HIV) drug... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid...

  3. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false In vitro human immunodeficiency virus (HIV) drug... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid...

  4. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false In vitro human immunodeficiency virus (HIV) drug... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid...

  5. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false In vitro human immunodeficiency virus (HIV) drug... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid...

  6. Quantitation of human immunodeficiency virus type 1 infection kinetics.

    PubMed Central

    Dimitrov, D S; Willey, R L; Sato, H; Chang, L J; Blumenthal, R; Martin, M A

    1993-01-01

    Tissue culture infections of CD4-positive human T cells by human immunodeficiency virus type 1 (HIV-1) proceed in three stages: (i) a period following the initiation of an infection during which no detectable virus is produced; (ii) a phase in which a sharp increase followed by a peak of released progeny virions can be measured; and (iii) a final period when virus production declines. In this study, we have derived equations describing the kinetics of HIV-1 accumulation in cell culture supernatants during multiple rounds of infection. Our analyses indicated that the critical parameter affecting the kinetics of HIV-1 infection is the infection rate constant k = Inn/ti, where n is the number of infectious virions produced by one cell (about 10(2)) and ti is the time required for one complete cycle of virus infection (typically 3 to 4 days). Of particular note was our finding that the infectivity of HIV-1 during cell-to-cell transmission is 10(2) to 10(3) times greater than the infectivity of cell-free virus stocks, the inocula commonly used to initiate tissue culture infections. We also demonstrated that the slow infection kinetics of an HIV-1 tat mutant is not due to a longer replication time but reflects the small number of infectious particles produced per cycle. PMID:8445728

  7. Recombination in feline immunodeficiency virus genomes from naturally infected cougars.

    PubMed

    Bruen, Trevor C; Poss, Mary

    2007-08-01

    Recombination contributes significantly to diversity within virus populations and ultimately to viral evolution. Here we use a recently developed statistical test to perform exploratory analysis of recombination in fourteen feline immunodeficiency virus (FIVpco) genomes derived from a wild population of cougars. We use both the global and local Phi statistical test as an overall guide to predict where recombination may have occurred. Further analyses, including similarity plots and phylogenetic incongruence tests, confirmed that three FIVpco lineages were derived from recombinant events. Interestingly, the regions of mosaic origin were clustered in the area encoding lentiviral accessory genes and largely spared the viral structural genes. Because some of the mosaic strains are currently geographically disparate, our data indicate that the dispersal of cougars infected with these strains was preceded by recombination events. These results suggest that recombination has played an important role in the evolution of FIVpco for this wild population of cougars.

  8. Multivariate analysis of human immunodeficiency virus type 1 neutralization data.

    PubMed Central

    Nyambi, P N; Nkengasong, J; Lewi, P; Andries, K; Janssens, W; Fransen, K; Heyndrickx, L; Piot, P; van der Groen, G

    1996-01-01

    We report on the use of spectral map analysis of the inter- and intraclade neutralization data of 14 sera of human immunodeficiency virus type 1 (HIV-1)-infected individuals and 16 primary isolates, representing genetic clades A to H in group M and group O. This multivariate analysis has been used previously to study the interaction between drugs and receptors and between viruses and antiviral compounds. The analysis reveals the existence of neutralization clusters, not correlated with the known genetic clades. The structural factors that have been identified may correlate with the most important neutralization epitopes. Three key primary HIV-1 isolates, which allow discrimination of sera that are likely or unlikely to neutralize primary isolates from most of the genetic clades, were identified. Our method of analysis will facilitate the evaluation as well as the design of suitable HIV-1 vaccines, which induce high-titer interclade cross-neutralizing antibodies. PMID:8709250

  9. Primary pulmonary hypertension associated with human immunodeficiency virus infection.

    PubMed Central

    Golpe, R.; Fernandez-Infante, B.; Fernandez-Rozas, S.

    1998-01-01

    Several cardiorespiratory diseases can complicate human immunodeficiency virus infection. Primary pulmonary hypertension is a rare clinical disorder which carries a bad prognosis. More than 90 cases of HIV-associated primary pulmonary hypertension have been reported to date. Although its pathogenesis remains unknown, some evidence suggests a possible role for the virus itself in its development. Genetic susceptibility may also be implicated. The clinical and histopathologic features of this entity do not differ from those of classic primary pulmonary hypertension. The diagnosis requires a high degree of clinical suspicion and a careful evaluation to rule out causes of secondary pulmonary hypertension. In addition to supportive measures, anticoagulation and vasodilators have been used to treat this disorder, although sufficient data regarding long-term results with these therapies are lacking. PMID:9799910

  10. Pro- and anti-inflammatory cytokines in human immunodeficiency virus infection and acquired immunodeficiency syndrome.

    PubMed

    Breen, Elizabeth Crabb

    2002-09-01

    In persons with human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS), the immune system becomes dysfunctional in many ways. There is both immunodeficiency due to the loss of CD4-positive T helper cells and hyperactivity as a result of B-cell activation. Likewise, both decreases and increases are seen in the production and/or activity of cytokines. Cytokine changes in HIV infection have been assessed by a variety of techniques, ranging from determination of cytokine gene expression at the mRNA level to secretion of cytokine proteins in vivo and in vitro. Changes in cytokine levels in HIV-infected persons can affect the function of the immune system, and have the potential to directly impact the course of HIV disease by enhancing or suppressing HIV replication. In particular, the balance between the pro-inflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha, which up-regulate HIV expression, and IL-10, which can act both as an anti-inflammatory cytokine and a B-cell stimulatory factor, may play an important role in the progression to AIDS. In light of its ability to suppress the production of pro-inflammatory cytokines and, under some conditions, suppress HIV replication, increased IL-10 may be viewed as beneficial in slowing HIV disease progression. However, an association between increased IL-10 and the development of AIDS-associated B-cell lymphoma highlights the bifunctional nature of IL-10 as both an anti-inflammatory and B-cell-stimulatory cytokine that could have beneficial and detrimental effects on the course of HIV infection and AIDS.

  11. Effects of dimethyl prostaglandin A1 on herpes simplex virus and human immunodeficiency virus replication

    NASA Technical Reports Server (NTRS)

    Hughes-Fulford, M.; McGrath, M. S.; Hanks, D.; Erickson, S.; Pulliam, L.

    1992-01-01

    We have investigated the direct effect of dimethyl prostaglandin A1 (dmPGA1) on the replication of herpes simplex virus (HSV) and human immunodeficiency virus type 1 (HIV-1). dmPGA1 significantly inhibited viral replication in both HSV and HIV infection systems at concentrations of dmPGA1 that did not adversely alter cellular DNA synthesis. The 50% inhibitory concentration (ID50) for several HSV type 1 (HSV-1) strains ranged from 3.8 to 5.6 micrograms/ml for Vero cells and from 4.6 to 7.3 micrograms/ml for human foreskin fibroblasts. The ID50s for two HSV-2 strains varied from 3.8 to 4.5 micrograms/ml for Vero cells; the ID50 was 5.7 micrograms/ml for human foreskin fibroblasts. We found that closely related prostaglandins did not have the same effect on the replication of HSV; dmPGE2 and dmPGA2 caused up to a 60% increase in HSV replication compared with that in untreated virus-infected cells. HIV-1 replication in acutely infected T cells (VB line) and chronically infected macrophages was assessed by quantitative decreases in p24 concentration. The effective ID50s were 2.5 micrograms/ml for VB cells acutely infected with HIV-1 and 5.2 micrograms/m for chronically infected macrophages. dmPGA1 has an unusual broad-spectrum antiviral activity against both HSV and HIV-1 in vitro and offers a new class of potential therapeutic agents for in vivo use.

  12. Cardiac dysfunction in patients seropositive for the human immunodeficiency virus.

    PubMed Central

    Johnson, J. E.; Slife, D. M.; Anders, G. T.; Bailey, S. R.; Blanton, H. M.; McAllister, C. K.; Latham, R. D.

    1991-01-01

    To confirm the presence of cardiac dysfunction in a group of patients seropositive for the human immunodeficiency virus with either dyspnea on exertion or a reduced anaerobic threshold, 9 patients with no history of opportunistic infection underwent exercise right-sided heart catheterization. When compared with 13 control patients previously exercised in the same manner, the patients showed elevated exercise pulmonary capillary wedge pressure (14.6 +/- 3.3 mm of mercury versus 9.9 +/- 3.3 mm of mercury; P less than .005) and right atrial pressure (10.1 +/- 2.1 mm of mercury versus 4.7 +/- 3.2 mm of mercury; P less than .001) at a similar exercise oxygen consumption and cardiac index. Of the 9 patients, 8 had at least 1 catheterization value outside the 95% confidence limits for the control group and 4 patients had multiple abnormalities. Values for blood CD4 lymphocytes were 0.2 x 10(9) per liter or more for 7 of the 9. One patient underwent endomyocardial biopsy with findings consistent with a cardiomyopathy. We conclude that cardiac disease may occur at any immunologic stage of human immunodeficiency virus infection. These observations suggest an effect of this disease on the heart. Images PMID:1771874

  13. Alternative nucleophilic substrates for the endonuclease activities of human immunodeficiency virus type 1 integrase

    SciTech Connect

    Ealy, Julie B.; Sudol, Malgorzata; Krzeminski, Jacek; Amin, Shantu; Katzman, Michael

    2012-11-10

    Retroviral integrase can use water or some small alcohols as the attacking nucleophile to nick DNA. To characterize the range of compounds that human immunodeficiency virus type 1 integrase can accommodate for its endonuclease activities, we tested 45 potential electron donors (having varied size and number or spacing of nucleophilic groups) as substrates during site-specific nicking at viral DNA ends and during nonspecific nicking reactions. We found that integrase used 22 of the 45 compounds to nick DNA, but not all active compounds were used for both activities. In particular, 13 compounds were used for site-specific and nonspecific nicking, 5 only for site-specific nicking, and 4 only for nonspecific nicking; 23 other compounds were not used for either activity. Thus, integrase can accommodate a large number of nucleophilic substrates but has selective requirements for its different activities, underscoring its dynamic properties and providing new information for modeling and understanding integrase.

  14. Prevention and treatment of human immunodeficiency virus/acquired immunodeficiency syndrome in resource-limited settings.

    PubMed Central

    Hogan, Daniel R.; Salomon, Joshua A.

    2005-01-01

    Strategies for confronting the epidemic of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) have included a range of different approaches that focus on prevention and treatment. However, debate persists over what levels of emphasis are appropriate for the different components of the global response. This paper presents an overview of this debate and briefly summarizes the evidence on a range of interventions designed to prevent the spread of HIV infection, paying particular attention to voluntary counselling and testing, treatment for sexually transmitted infections and prevention of mother-to-child transmission. We also review the experience with antiretroviral therapy to date in terms of response rates and survival rates, adherence, drug resistance, behavioural change and epidemiological impact. Although various studies have identified strategies with proven effectiveness in reducing the risks of HIV infection and AIDS mortality, considerable uncertainties remain. Successful integration of treatment and prevention of HIV/AIDS will require a balanced approach and rigorous monitoring of the impact of programmes in terms of both individual and population outcomes. PMID:15744406

  15. The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus encephalitis: deficits in cognitive function.

    PubMed

    Griffin, William C; Middaugh, Lawrence D; Cook, Jennifer E; Tyor, William R

    2004-04-01

    The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus (HIV) encephalitis exhibits many of the histopathological and pathophysiological features of human HIV-associated dementia (HAD). Although deficits that may resemble HAD in humans have been reported for HIV-infected SCID mice, the cognitive deficit aspect of the model has very limited empirical support. Here, the authors report that HIV-infected SCID mice display cognitive deficits on a task requiring the animal to learn and remember the spatial relationship of cues in its environment in order to locate a submerged platform in a Morris water maze. The cognitive deficits manifest as longer latencies to locate the platform on the last day of the maze acquisition period and during a retention test 8 days later. Control experiments indicated that the poor performance by HIV-infected mice in comparison to controls was not due to impaired motor function or swimming ability, impaired visual acuity, or increased susceptibility to fatigue. Thus, the increased times required for HIV-infected mice to locate the submerged platform during the acquisition and memory tests likely reflect a cognitive deficit, rather than sensorimotor or emotional abnormalities. These behavioral deficits are associated with significant increases in astrogliosis and microgliosis in the HIV-infected mice. The results of this study strengthen the SCID mouse model of HIV encephalitis by definitively establishing cognitive deficits for the model in addition to its previously reported neuropathological features.

  16. Inhibition of Human Immunodeficiency Virus Type 1 by Triciribine Involves the Accessory Protein Nef ▿

    PubMed Central

    Ptak, Roger G.; Gentry, Brian G.; Hartman, Tracy L.; Watson, Karen M.; Osterling, M. Clayton; Buckheit, Robert W.; Townsend, Leroy B.; Drach, John C.

    2010-01-01

    Triciribine (TCN) is a tricyclic nucleoside that inhibits human immunodeficiency virus type 1 (HIV-1) replication by a unique mechanism not involving the inhibition of enzymes directly involved in viral replication. This activity requires the phosphorylation of TCN to its 5′ monophosphate by intracellular adenosine kinase. New testing with a panel of HIV and simian immunodeficiency virus isolates, including low-passage-number clinical isolates and selected subgroups of HIV-1, multidrug resistant HIV-1, and HIV-2, has demonstrated that TCN has broad antiretroviral activity. It was active in cell lines chronically infected with HIV-1 in which the provirus was integrated into chromosomal DNA, thereby indicating that TCN inhibits a late process in virus replication. The selection of TCN-resistant HIV-1 isolates resulted in up to a 750-fold increase in the level of resistance to the drug. DNA sequence analysis of highly resistant isolate HIV-1H10 found five point mutations in the HIV-1 gene nef, resulting in five different amino acid changes. DNA sequencing of the other TCN-resistant isolates identified at least one and up to three of the same mutations observed in isolate HIV-1H10. Transfer of the mutations from TCN-resistant isolate HIV-1H10 to wild-type virus and subsequent viral growth experiments with increasing concentrations of TCN demonstrated resistance to the drug. We conclude that TCN is a late-phase inhibitor of HIV-1 replication and that mutations in nef are necessary and sufficient for TCN resistance. PMID:20086149

  17. Intensifying Antiretroviral Therapy With Raltegravir and Maraviroc During Early Human Immunodeficiency Virus (HIV) Infection Does Not Accelerate HIV Reservoir Reduction.

    PubMed

    Ostrowski, Mario; Benko, Erika; Yue, Feng Yun; Kim, Connie J; Huibner, Sanja; Lee, Terry; Singer, Joel; Pankovich, Jim; Laeyendecker, Oliver; Kaul, Rupert; Kandel, Gabor; Kovacs, Colin

    2015-12-01

    Background.  Persistent human immunodeficiency virus (HIV) within the CD4(+) T-cell reservoir is an obstacle to eradication. We hypothesized that adding raltegravir and maraviroc to standard combination antiretroviral therapy (cART) during early HIV infection could substantially reduce viral reservoirs as a step towards eradication. Methods.  A prospective, randomized, double-blinded, placebo-controlled pilot trial enrolled 32 participants with documented early (<6 months) HIV infection to either standard cART (emtricitabine/tenofovir/lopinavir/ritonavir) or intensive cART (standard regimen + raltegravir/maraviroc). Human immunodeficiency virus reservoirs were assessed at baseline and at 48 weeks by (1) proviral DNA, (2) cell-associated RNA, and (3) replication-competent virus, all from purified blood CD4(+) T cells, and (4) gut proviral DNA. A multiassay algorithm (MAA) on baseline sera estimated timing of infection. Results.  Thirty individuals completed the study to the 48-week endpoint. The reduction in blood proviral burden was -1.03 log DNA copies/10(6) CD4(+) T cells versus -.84 log in the standard and intensive groups, respectively (P = .056). Overall, there was no significant difference in the rate of decline of HIV-associated RNA, replication-competent virus in blood CD4(+) T cells, nor proviral gut HIV DNA to 48 weeks. Individuals who presented with more recent HIV infection had significantly lower virus reservoirs, and cART tended to reduce their reservoirs to a greater extent. Conclusions.  Intensive cART led to no additional reduction in the blood virus reservoir at 48 weeks compared with standard cART. Human immunodeficiency virus reservoir size is smaller earlier in HIV infection. Other novel treatment strategies in combination with early cART will be needed to eliminate the HIV latent reservoir.

  18. Septic arthritis in patients with acquired immunodeficiency syndrome with human immunodeficiency virus infection.

    PubMed

    Rivera, J; Monteagudo, I; Lopez-Longo, J; Sanchez-Atrio, A

    1992-12-01

    We have evaluated the presence and characteristics of septic arthritis in intravenous (iv) drug users with human immunodeficiency virus (HIV) infection. Sixteen patients with both HIV infection and septic arthritis were studied and compared with 5 patients with septic arthritis but no HIV infection. Clinical profile, laboratory findings at the time of onset, localization, causative organisms, mean hospitalization time and presence of complications were the same in HIV positive and HIV negative patients. Staphylococcus aureus was the most commonly isolated organism in both groups. We conclude that septic arthritis in HIV infected iv drug users is not uncommon, it is produced by the same organisms and presents similar characteristics to the ones found in iv drug users without HIV infection. Therefore, the presence of HIV infection does not appear to modify the characteristics of septic arthritis.

  19. Kinetics of human immunodeficiency virus budding and assembly

    NASA Astrophysics Data System (ADS)

    Zhang, Rui; Nguyen, Toan

    2009-03-01

    Human immunodeficiency virus (HIV) belongs to a large family of RNA viruses, retroviruses. Unlike budding of regular enveloped viruses, retroviruses bud concurrently with the assembly of retroviral capsids on the cell membrane. The kinetics of HIV (and other retroviruses) budding and assembly is therefore strongly affected by the elastic energy of the membrane and fundamentally different from regular viruses. The main result of this work shows that the kinetics is tunable from a fast budding process to a slow and effectively trapped partial budding process, by varying the attractive energy of retroviral proteins (call Gags), relative to the membrane elastic energy. When the Gag-Gag attraction is relatively high, the membrane elastic energy provides a kinetic barrier for the two pieces of the partial capsids to merge. This energy barrier determines the slowest step in the kinetics and the budding time. In the opposite limit, the membrane elastic energy provides not only a kinetic energy barrier, but a free energy barrier. The budding and assembly is effectively trapped at local free energy minimum, corresponding to a partially budded state. The time scale to escape from this metastable state is exponentially large. In both cases, our result fit with experimental measurements pretty well.

  20. Molecular detection of bovine immunodeficiency virus in water buffaloes (Bubalus bubalis) from the Amazon region, Brazil.

    PubMed

    Albernaz, Tatiane Teles; Leite, Rômulo Cerqueira; Reis, Jenner Karlison Pimenta; de Sousa Rodrigues, Ana Paula; da Cunha Kassar, Telissa; Resende, Claudia Fideles; de Oliveira, Cairo Henrique Sousa; Silva, Rafaela das Mercês; Salvarani, Felipe Masiero; Barbosa, José Diomedes

    2015-12-01

    Bovine immunodeficiency is a chronic progressive disease caused by a lentivirus that affects cattle and buffaloes. Although the infection has been described in cattle in some countries, including in Brazil, there are only two reports of infection in buffaloes: one in Pakistan and one in Cambodia. The aim of the present study was to survey the occurrence of bovine immunodeficiency virus (BIV) in water buffaloes from the Amazon region, Pará state, Brazil. BIV proviral DNA was surveyed in 607 whole blood samples of water buffaloes from 10 farms located in the state of Pará using semi-nested polymerase chain reaction (PCR) (PCR-SN) to amplify the pol region of the viral genome. Of the 607 samples tested, 27 (4.4 %) were positive for BIV proviral DNA. The amplified fragments were confirmed by sequence analysis after cloning and nucleotide sequencing. The sequence obtained had 99 % similarity to the reference strain (R-29). The present study provides important epidemiological data because BIV was detected for the first time in water buffaloes in Brazil. Further, the results suggest the possibility of the virus being a risk factor for herd health because it may be a potential causal agent of chronic disease and, also may be associated to other infectious diseases.

  1. Safety and Tolerability of Conserved Region Vaccines Vectored by Plasmid DNA, Simian Adenovirus and Modified Vaccinia Virus Ankara Administered to Human Immunodeficiency Virus Type 1-Uninfected Adults in a Randomized, Single-Blind Phase I Trial

    PubMed Central

    Hayton, Emma-Jo; Rose, Annie; Ibrahimsa, Umar; Del Sorbo, Mariarosaria; Capone, Stefania; Crook, Alison; Black, Antony P.; Dorrell, Lucy; Hanke, Tomáš

    2014-01-01

    Trial Design HIV-1 vaccine development has advanced slowly due to viral antigenic diversity, poor immunogenicity and recently, safety concerns associated with human adenovirus serotype-5 vectors. To tackle HIV-1 variation, we designed a unique T-cell immunogen HIVconsv from functionally conserved regions of the HIV-1 proteome, which were presented to the immune system using a heterologous prime-boost combination of plasmid DNA, a non-replicating simian (chimpanzee) adenovirus ChAdV-63 and a non-replicating poxvirus, modified vaccinia virus Ankara. A block-randomized, single-blind, placebo-controlled phase I trial HIV-CORE 002 administered for the first time candidate HIV-1- vaccines or placebo to 32 healthy HIV-1/2-uninfected adults in Oxford, UK and elicited high frequencies of HIV-1-specific T cells capable of inhibiting HIV-1 replication in vitro. Here, detail safety and tolerability of these vaccines are reported. Methods Local and systemic reactogenicity data were collected using structured interviews and study-specific diary cards. Data on all other adverse events were collected using open questions. Serum neutralizing antibody titres to ChAdV-63 were determined before and after vaccination. Results Two volunteers withdrew for vaccine-unrelated reasons. No vaccine-related serious adverse events or reactions occurred during 190 person-months of follow-up. Local and systemic events after vaccination occurred in 27/32 individuals and most were mild (severity grade 1) and predominantly transient (<48 hours). Myalgia and flu-like symptoms were more strongly associated with MVA than ChAdV63 or DNA vectors and more common in vaccine recipients than in placebo. There were no intercurrent HIV-1 infections during follow-up. 2/24 volunteers had low ChAdV-63-neutralizing titres at baseline and 7 increased their titres to over 200 with a median (range) of 633 (231-1533) post-vaccination, which is of no safety concern. Conclusions These data demonstrate safety and good

  2. Infection of bovine immunodeficiency virus and bovine leukemia virus in water buffalo and cattle populations in Pakistan.

    PubMed

    Meas, S; Seto, J; Sugimoto, C; Bakhsh, M; Riaz, M; Sato, T; Naeem, K; Ohashi, K; Onuma, M

    2000-03-01

    A survey of antibodies to bovine immunodeficiency virus (BIV) known as bovine lentivirus and bovine leukemia virus (BLV) was conducted with samples from water buffalo and cattle populations in Pakistan. A total of 370 water buffaloes and 76 cattle were tested, and 10.3% and 15.8%, respectively, were found positive for anti-BIV p26 antibodies determined by Western blotting, while 0.8% of water buffaloes and no cattle were positive for anti-BLV antibodies determined by immunodiffusion test. BIV-seropositive water buffaloes and cattle were found to have BIV proviral DNA in the peripheral blood mononuclear cells determined by nested polymerase chain reaction. This is the first report of BIV infections in water buffaloes.

  3. Oral lesions in infection with human immunodeficiency virus.

    PubMed Central

    Coogan, Maeve M.; Greenspan, John; Challacombe, Stephen J.

    2005-01-01

    This paper discusses the importance of oral lesions as indicators of infection with human immunodeficiency virus (HIV) and as predictors of progression of HIV disease to acquired immunodeficiency syndrome (AIDS). Oral manifestations are among the earliest and most important indicators of infection with HIV. Seven cardinal lesions, oral candidiasis, hairy leukoplakia, Kaposi sarcoma, linear gingival erythema, necrotizing ulcerative gingivitis, necrotizing ulcerative periodontitis and non-Hodgkin lymphoma, which are strongly associated with HIV infection, have been identified and internationally calibrated, and are seen in both developed and developing countries. They may provide a strong indication of HIV infection and be present in the majority of HIV-infected people. Antiretroviral therapy may affect the prevalence of HIV-related lesions. The presence of oral lesions can have a significant impact on health-related quality of life. Oral health is strongly associated with physical and mental health and there are significant increases in oral health needs in people with HIV infection, especially in children, and in adults particularly in relation to periodontal diseases. International collaboration is needed to ensure that oral aspects of HIV disease are taken into account in medical programmes and to integrate oral health care with the general care of the patient. It is important that all health care workers receive education and training on the relevance of oral health needs and the use of oral lesions as surrogate markers in HIV infection. PMID:16211162

  4. Seroprevalence of Toxoplasma gondii and concurrent Bartonella spp., feline immunodeficiency virus, feline leukemia virus, and Dirofilaria immitis infections in Egyptian cats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Toxoplasma gondii and Bartonella spp. are zoonotic pathogens of cats. Feline Immunodeficiency Virus (FIV), and Feline Leukemia Virus (FeLv) are related to Human Immunodeficiency Virus, and Human Leukemia Virus, respectively, and these viruses are immunosuppressive. In the present study, the prevalen...

  5. Methods for assessing feline immunodeficiency virus infection, infectivity and purification.

    PubMed

    Ammersbach, Melanie; Bienzle, Dorothee

    2011-10-15

    Infection of cats with the feline immunodeficiency virus (FIV) recapitulates many aspects of infection of humans with HIV, including highly activated but ineffectual immune responses. Infected hosts remain seropositive for life, and detection of antibodies is the mainstay of diagnosis. However, to quantify virus for research or prognosis, viral proteins, nucleic acids or enzymes, are typically measured by ELISA, PCR or activity, respectively. While such assays are in wide use, they do not distinguish whole, infectious viral particles from defective or disrupted viruses. Titers of infectious viral particles may be estimated from tissue culture infectious doses or by enumerating cell-associated viral proteins, viral transcriptional activity or formation of syncytia. To analyze the viral proteome and the incorporation of host components into viral envelopes, pure lentiviral preparations are required. Methods for purifying lentiviruses include ultracentrifugation to separate particles by size, mass and/or density; chromatography to separate particles by charge, affinity or size; and additional removal of extraviral proteins and exosomes through subtilisin digestion or immunoaffinity. This article reviews advantages and disadvantages of different approaches to purification of lentiviruses with special reference to suitability for FIV, and highlights effects of purification on immune responses and immune assays. PMID:21715023

  6. Conserved serines in simian immunodeficiency virus capsid are required for virus budding.

    PubMed

    Rue, Sarah M; Roos, Jason W; Clements, Janice E; Barber, Sheila A

    2005-05-25

    The simian immunodeficiency virus (SIV) capsid protein (CA), a constituent of the Pr55Gag polyprotein, is phosphorylated in virions but not in virus-producing cells (Rue, S.M., Roos, J.W., Tarwater, P.M., Clements, J.E., Barber, S.A., 2005. Phosphorylation and proteolytic cleavage of gag proteins in budded simian immunodeficiency virus. J. Virol. 79 (4), 2484-2492.). Using phosphoamino acid analysis of CA, we show that serine is the primary phosphate acceptor. A series of substitution mutants of serines in the CA domain of Pr55Gag were constructed in the infectious viral clone SIVmac239. These virus mutants were examined for defects in virus replication and virion infectivity, release, and morphology, as well as alterations in phosphorylation of CA-containing proteins. Although the virus mutants exhibited a number of replication defects, none of these defects could be directly attributed to aberrant CA phosphorylation. A novel defect was a block in early budding, which was common among several virus mutants with substitutions in the CA N terminus. Together, these results indicate that certain residues in the CA N terminus are crucial for early budding events.

  7. Follicular dendritic cells and human immunodeficiency virus infectivity

    NASA Astrophysics Data System (ADS)

    Heath, Sonya L.; Tew, J. Grant; Tew, John G.; Szakal, Andras K.; Burton, Gregory F.

    1995-10-01

    LARGE amounts of human immunodeficiency virus (HIV) localize on follicular dendritic cells (FDC) in the follicles of secondary lymphoid tissues following viral infection1,2. During clinical latency, active viral infection occurs primarily at these sites3,4. As HIV on FDC is in the form of immune complexes5, some of which may be formed with neutralizing antibody, we investigated whether HIV on FDC is infectious. We report here that HIV on FDC is highly infectious. Furthermore, FDC can convert neutralized HIV into an infectious form even in the presence of a vast excess of neutralizing antibody. Thus FDC may provide a mechanism whereby HIV infection can continue in the presence of neutralizing antibody.

  8. Human immunodeficiency virus antibody test and seroprevalence in psychiatric patients.

    PubMed

    Naber, D; Pajonk, F G; Perro, C; Löhmer, B

    1994-05-01

    Psychiatric inpatients are at risk for human immunodeficiency virus (HIV) infection. Investigations in the United States revealed seroprevalence rates of 5.5-8.9%. Therefore, inclusion of HIV antibody testing in routine laboratory screening is sometimes suggested. To investigate this issue for inpatients in the Department of Psychiatry, University of Munich, the incidence, reason for HIV testing and results were analyzed. Of 12,603 patients, hospitalized from 1985 to 1993, 4.9% (623 patients, 265 in risk groups) underwent the HIV test after informed consent. Thirty patients (4.8% of those tested) were found to be positive, but only in 5 cases (all of risk groups) was infection newly detected. Data indicate that, in psychiatry, HIV testing is reasonable only in patients in risk groups or if clinical variables suggest HIV infection.

  9. Renal involvement in feline immunodeficiency virus infection: a clinicopathological study.

    PubMed

    Poli, A; Abramo, F; Taccini, E; Guidi, G; Barsotti, P; Bendinelli, M; Malvaldi, G

    1993-01-01

    Renal tissues from 15 cats naturally infected with feline immunodeficiency virus (FIV) were examined histologically, immunohistochemically and ultrastructurally. Renal function and urinary proteins were also studied. Kidney abnormalities were found in 12 cats and were characterized by mesangial widening with segmental to diffuse glomerulosclerosis and presence of IgM and C3, and scanty IgG deposits in the mesangium. Tubulointerstitial lesions were also present. In 6 cats the lesions were severe enough to cause marked increase in blood urea nitrogen and creatinine, and heavy glomerular nonselective proteinuria. These findings suggest that a renal involvement is a frequent occurrence in FIV-infected cats. As the histopathological features observed were similar to those described in HIV-infected patients, FIV-infected cats may represent a valuable model for a better understanding of HIV-associated nephropathy in humans. PMID:8321363

  10. Human immunodeficiency virus and migrant labor in South Africa.

    PubMed

    Jochelson, K; Mothibeli, M; Leger, J P

    1991-01-01

    The authors investigate the impact of the migrant labor system on heterosexual relationships on South African mines and assess the implications for the future transmission of human immunodeficiency virus (HIV) infection. The migrant labor system has created a market for prostitution in mining towns and geographic networks of relationships within and between urban and rural communities. A section of the migrant workforce and a group of women dependent on prostitution for economic support appear especially vulnerable to contracting HIV infection since they are involved in multiple sexual encounters with different, changing partners, usually without condom protection. Furthermore, sexually transmitted disease morbidity is extensive in the general and mineworker populations. Historically, migration facilitated the transmission of sexually transmitted diseases and may act similarly for HIV. Problems of combating the HIV epidemic in South Africa are discussed. PMID:2004869

  11. Seroprevalence of human immunodeficiency virus among inpatient pretrial detainees.

    PubMed

    Schwartz-Watts, D; Montgomery, L D; Morgan, D W

    1995-01-01

    Medical records of inpatients discharged from a forensic unit in Columbia, South Carolina, from January 1991 to December 1991 were reviewed to determine the incidence of human immunodeficiency virus (HIV) seropositivity. Results were linked to age, gender, ethnicity, history of intravenous drug use, and Axis I diagnoses. HIV status was obtained for 74 percent of patients 18 to 55 years of age. The incidence of HIV seropositivity among patients tested was 5.5 percent, which is greater than 40 times the incidence for the general population in South Carolina. Intravenous drug use was reported for 33 percent of the seropositive males. We conclude that inpatient pretrial detainees are at increased risk for HIV infection. HIV testing should be mandated at all facilities housing detainees. Further studies are needed to determine any factors about these patients that can be linked to seropositivity.

  12. Human immunodeficiency virus and migrant labor in South Africa.

    PubMed

    Jochelson, K; Mothibeli, M; Leger, J P

    1991-01-01

    The authors investigate the impact of the migrant labor system on heterosexual relationships on South African mines and assess the implications for the future transmission of human immunodeficiency virus (HIV) infection. The migrant labor system has created a market for prostitution in mining towns and geographic networks of relationships within and between urban and rural communities. A section of the migrant workforce and a group of women dependent on prostitution for economic support appear especially vulnerable to contracting HIV infection since they are involved in multiple sexual encounters with different, changing partners, usually without condom protection. Furthermore, sexually transmitted disease morbidity is extensive in the general and mineworker populations. Historically, migration facilitated the transmission of sexually transmitted diseases and may act similarly for HIV. Problems of combating the HIV epidemic in South Africa are discussed.

  13. Glanzmann Thrombasthenia Associated with Human Immunodeficiency Virus-Positive Patient

    PubMed Central

    Manne, Rakesh Kumar; Natarajan, Kannan; Patil, Rajendra; Prathi, Venkata Sarath; Beeraka, Swapna Sridevi; Kolaparthi, Venkata Suneel Kumar

    2014-01-01

    Glanzmann's thrombasthenia (GT) is an autosomal recessive inherited platelet function defect characterized by normal platelet count, prolonged bleeding time and abnormal clot retraction. This disease typically presents in infancy or early childhood and has proven to have very good prognosis. In this case study, a 22-year-old GT patient who also developed human immunodeficiency virus (HIV) infection after sometime is reported. The patient showed oral manifestations of gingival hyperplasia and petechial lesions. Unfortunately the detection of both thrombasthenia and HIV were done at considerably late stages which contributed to a poor prognosis. The patient died of cardiopulmonary arrest secondary to HIV, thrombasthenia and thrombocytopenia. The importance of early detection, supportive care and communication between the general and oral physician in management of the GT is also discussed. PMID:24829739

  14. Human immunodeficiency virus antibody test and seroprevalence in psychiatric patients.

    PubMed

    Naber, D; Pajonk, F G; Perro, C; Löhmer, B

    1994-05-01

    Psychiatric inpatients are at risk for human immunodeficiency virus (HIV) infection. Investigations in the United States revealed seroprevalence rates of 5.5-8.9%. Therefore, inclusion of HIV antibody testing in routine laboratory screening is sometimes suggested. To investigate this issue for inpatients in the Department of Psychiatry, University of Munich, the incidence, reason for HIV testing and results were analyzed. Of 12,603 patients, hospitalized from 1985 to 1993, 4.9% (623 patients, 265 in risk groups) underwent the HIV test after informed consent. Thirty patients (4.8% of those tested) were found to be positive, but only in 5 cases (all of risk groups) was infection newly detected. Data indicate that, in psychiatry, HIV testing is reasonable only in patients in risk groups or if clinical variables suggest HIV infection. PMID:8067276

  15. Eosinophilia in Patients Infected with Human Immunodeficiency Virus

    PubMed Central

    Chou, Andrew; Serpa, Jose A.

    2015-01-01

    Eosinophilia is not uncommonly encountered in patients infected with human immunodeficiency virus (HIV); particularly at initiation of care or among those with advanced disease. The clinical manifestation most commonly associated with eosinophilia in this patient population is skin rash. Management of these patients is challenging due to a paucity of data evaluating diagnostic testing and therapeutic strategies. Patients born in or with significant travel to parasite-endemic countries are more likely to have tissue-invasive helminthes, such as Strongyloides or Schistosoma. Patients without such risk factors are unlikely to have parasitic infections and frequently will have self-resolution of eosinophilia. When a detailed history, physical exam and diagnostic work-up is unrevealing, we sometimes consider empirical therapy with ivermectin. Praziquantel may also be considered for those at risk for schistosomiasis. PMID:26126686

  16. Association of infections with human immunodeficiency virus and human papillomavirus in Honduras.

    PubMed

    Ferrera, A; Melchers, W J; Velema, J P; Figueroa, M

    1997-08-01

    The etiologic role of the oncogenic types of human papillomavirus (HPV) in the development of cervical cancer has been widely proven. Since this cancer occurs more frequently in immunosuppressed individuals, we sought to evaluate the prevalence of HPV infection among human immunodeficiency virus (HIV)-infected and HIV-noninfected prostitutes in Tegucigalpa, Honduras. Cervical scrapes were collected from 23 HIV-seropositive and 28 HIV-seronegative prostitutes for HPV DNA detection by the polymerase chain reaction. Fifty-six percent of the HIV-seropositive women and only 18% of the seronegative women were HPV DNA positive (odds ratio = 6.0). In addition, there was a significant association between seropositivity for HIV with a history of sexually transmitted diseases (P < 0.01). Our data confirm the association between infections with HIV and HPV.

  17. Very low prevalence of bovine immunodeficiency virus infection in western Canadian cattle.

    PubMed Central

    Gonzalez, G C; Johnston, J B; Nickel, D D; Jacobs, R M; Olson, M; Power, C

    2001-01-01

    Bovine immunodeficiency virus (BIV) is a lentivirus that causes disease in cattle. Despite the large cattle industry in western Canada, the presence of BIV has not been examined to date. Genomic DNA, derived from semen and buffy coat samples, was analyzed by nested polymerase chain reaction (PCR) using specific primers for the gag, pol, and env genes of BIV. Despite utilizing a procedure that detected a minimum of 10 proviral copies, BIV sequences were not amplified in any of 317 buffy coat and 50 semen samples that were obtained from an archive that included 27 cattle breeds, collected from different sources in Alberta (1980-1999). In the 367 DNA samples examined, there was no evidence of BIV infection, suggesting that the prevalence of BIV infection was very low. Images Figure 2. Figure 3. PMID:11227201

  18. Nuclear entry of DNA viruses

    PubMed Central

    Fay, Nikta; Panté, Nelly

    2015-01-01

    DNA viruses undertake their replication within the cell nucleus, and therefore they must first deliver their genome into the nucleus of their host cells. Thus, trafficking across the nuclear envelope is at the basis of DNA virus infections. Nuclear transport of molecules with diameters up to 39 nm is a tightly regulated process that occurs through the nuclear pore complex (NPC). Due to the enormous diversity of virus size and structure, each virus has developed its own strategy for entering the nucleus of their host cells, with no two strategies alike. For example, baculoviruses target their DNA-containing capsid to the NPC and subsequently enter the nucleus intact, while the hepatitis B virus capsid crosses the NPC but disassembles at the nuclear side of the NPC. For other viruses such as herpes simplex virus and adenovirus, although both dock at the NPC, they have each developed a distinct mechanism for the subsequent delivery of their genome into the nucleus. Remarkably, other DNA viruses, such as parvoviruses and human papillomaviruses, access the nucleus through an NPC-independent mechanism. This review discusses our current understanding of the mechanisms used by DNA viruses to deliver their genome into the nucleus, and further presents the experimental evidence for such mechanisms. PMID:26029198

  19. Resistance of previously infected chimpanzees to successive challenges with a heterologous intraclade B strain of human immunodeficiency virus type 1.

    PubMed Central

    Shibata, R; Siemon, C; Cho, M W; Arthur, L O; Nigida, S M; Matthews, T; Sawyer, L A; Schultz, A; Murthy, K K; Israel, Z; Javadian, A; Frost, P; Kennedy, R C; Lane, H C; Martin, M A

    1996-01-01

    To test whether the protective effects of attenuated simian immunodeficiency virus vaccines in macaques were applicable to the human immunodeficiency virus type 1 (HIV-1)-chimpanzee system, two groups of animals, previously infected with HIV-1(IIIB) or HIV-1(SF2) were each challenged with a heterologous clade B virus, HIV-1(DH12). Following challenge, the parameters measured included virus isolation (from plasma, peripheral blood mononuclear cells, and lymph node tissue); quantitative DNA PCR using primers capable of distinguishing HIV-1(IIIB), HIV-1(SF2), and HIV-1(DH12) from one another; and serologic assays to monitor changes in binding and neutralizing antibodies. In contrast to an HIV-1-naive chimpanzee that rapidly became infected following the inoculation of HIV-1(DH12), the two chimpanzees previously infected with HIV-1(IIIB) resisted repeated and escalating inoculations of HIV-1(DH12), as monitored by virus isolation and PCR. The two animals previously infected with HIV-1(SF2) became infected with HIV-1(DH12) but in contrast to the case with the HIV-1-naive chimpanzee, no cell-free viral RNA was detected in the plasma by the branched DNA procedure and levels of peripheral blood mononuclear cell-associated viral DNA were reduced 35- to 50-fold. PMID:8676459

  20. Analysis of the viral determinants underlying replication kinetics and cellular tropism of human immunodeficiency virus.

    PubMed

    Nagashunmugam, T; Velpandi, A; Otsuka, T; Cartas, M; Srinivasan, A

    1992-01-01

    Human immunodeficiency viruses (HIVs) isolated from infected individuals show genetic and biological diversity. To delineate the genetic determinants underlying specific biological characteristics such as rate of replication and cellular tropism, generation of hybrid HIV using viruses which exhibit distinct biological feature is essential. We have used three different infectious HIV proviral DNAs, designated pZ6, pHXB2 and pARV, derived from HIVZr6, HIVHTLV-IIIB and HIVSF-2 strains, respectively, to construct hybrid HIV. Proviral DNAs differed in their ability to direct the synthesis of viral particles upon transfection into cells and the viruses derived from the molecular clones exhibited different cellular tropism. Three different methods were utilized to generate hybrid HIV, including construction of hybrid proviral DNA using molecular techniques, intracellular ligation of viral DNA fragments and the homologous recombination approach. The chimeric proviral DNAs with exchanges involving only the long terminal repeat (LTR) region indicated that LTR does not exert influence on the overall level of virus production despite extensive differences in the U3 region of the LTR. Regarding the cellular tropism of HIV, the virus derived from pHXB2 productively infected CEMx174 cells. On the other hand, pARV-derived virus did not show productive infection of CEMx174 cells. The hybrid HIV containing the 3'-end of the genome from pARV and the 5'-end of the genome from pHXB2 was effective in infecting CEMx174 cells. However, the converse hybrid containing the 5'-pARV and the 3'-pHXB2 was not effective in infecting CEMx174 cells. These results suggest that differences in the genes outside of env and nef may play a role in the ability of virus to infect a certain cell type.

  1. Development of Methods for Coordinate Measurement of Total Cell-Associated and Integrated Human Immunodeficiency Virus Type 1 (HIV-1) DNA Forms in Routine Clinical Samples: Levels Are Not Associated with Clinical Parameters, but Low Levels of Integrated HIV-1 DNA May Be Prognostic for Continued Successful Therapy▿

    PubMed Central

    Carr, J. M.; Cheney, K. M.; Coolen, C.; Davis, A.; Shaw, D.; Ferguson, W.; Chang, G.; Higgins, G.; Burrell, C.; Li, P.

    2007-01-01

    We have adapted our established Alu PCR assay for proviral DNA and PCR for total cellular DNA to a real-time PCR format and applied these to human immunodeficiency virus (HIV)-positive specimens collected for routine determination of the plasma viral load (pVL). In a cohort of five patients, measurements of integrated viral load (iVL) and cell-associated viral load (cVL) in CD4+ cells isolated by a single positive selection step were not indicative of HIV DNA levels in the circulation, and further analysis was performed on peripheral blood mononuclear cells (PBMC). In a cohort of 46 samples total cVL was quantitated in most samples, but iVL could be quantitated in only 47.8%, since in 26% iVL was undetectable and in 21.7% the results were invalid due to high levels of unintegrated HIV DNA. There was no correlation of cVL or iVL with pVL, CD4 count, or duration of successful antiretroviral treatment. Out of 26 patients with undetectable pVL, 4 patients failed therapy within the subsequent 12 months and had higher than average iVL, but this was not the case for cVL. Among nine patients with long-term undetectable pVL, no consistent decline in cVL or iVL was seen with time, and changes in cVL and iVL within a patient could be concordant or discordant. These results show that cVL and iVL can be coordinately measured in PBMC from clinical samples but do not correlate with pVL, CD4 counts, or length of suppressive antiretroviral therapy. Interestingly, a high iVL (but not a high cVL) in patients with undetectable pVL was associated with subsequent treatment failure. PMID:17314225

  2. Coinfection with multiple strains of the Epstein-Barr virus in human immunodeficiency virus-associated hairy leukoplakia.

    PubMed Central

    Walling, D M; Edmiston, S N; Sixbey, J W; Abdel-Hamid, M; Resnick, L; Raab-Traub, N

    1992-01-01

    Epstein-Barr virus DNA was analyzed from specimens of hairy leukoplakia, an oral lesion that occurs in patients infected with the human immunodeficiency virus. The simultaneous presence of both type 1 and type 2 Epstein-Barr virus was demonstrated by Southern blot analysis and polymerase chain reaction assay. Restriction fragment length polymorphisms in the BamHI WYH region and in clones of the EcoRI C region suggested the presence of multiple strains of type 1 and type 2 viruses. The demonstration of multiple variably sized BamHI H fragments on Southern blot analysis and cloning of the EBNA-2 gene coding region also suggested the presence of multiple viral strains or variants coinfecting hairy leukoplakia. Recombination of the viral genome in and around the EBNA-2 gene apparently generated viral variants that replicated efficiently, one of which appeared to increase in abundance in a lesion over time. These data indicate that hairy leukoplakia involves coinfection with multiple strains of replicating Epstein-Barr virus and the endogenous generation of viral variants, some of which have mutations of the EBNA-2 gene. Images PMID:1321443

  3. Human immunodeficiency virus and acquired immunodeficiency syndrome: correlation but not causation.

    PubMed Central

    Duesberg, P H

    1989-01-01

    AIDS is an acquired immunodeficiency syndrome defined by a severe depletion of T cells and over 20 conventional degenerative and neoplastic diseases. In the U.S. and Europe, AIDS correlates to 95% with risk factors, such as about 8 years of promiscuous male homosexuality, intravenous drug use, or hemophilia. Since AIDS also correlates with antibody to a retrovirus, confirmed in about 40% of American cases, it has been hypothesized that this virus causes AIDS by killing T cells. Consequently, the virus was termed human immunodeficiency virus (HIV), and antibody to HIV became part of the definition of AIDS. The hypothesis that HIV causes AIDS is examined in terms of Koch's postulates and epidemiological, biochemical, genetic, and evolutionary conditions of viral pathology. HIV does not fulfill Koch's postulates: (i) free virus is not detectable in most cases of AIDS; (ii) virus can only be isolated by reactivating virus in vitro from a few latently infected lymphocytes among millions of uninfected ones; (iii) pure HIV does not cause AIDS upon experimental infection of chimpanzees or accidental infection of healthy humans. Further, HIV violates classical conditions of viral pathology. (i) Epidemiological surveys indicate that the annual incidence of AIDS among antibody-positive persons varies from nearly 0 to over 10%, depending critically on nonviral risk factors. (ii) HIV is expressed in less than or equal to 1 of every 10(4) T cells it supposedly kills in AIDS, whereas about 5% of all T cells are regenerated during the 2 days it takes the virus to infect a cell. (iii) If HIV were the cause of AIDS, it would be the first virus to cause a disease only after the onset of antiviral immunity, as detected by a positive "AIDS test." (iv) AIDS follows the onset of antiviral immunity only after long and unpredictable asymptomatic intervals averaging 8 years, although HIV replicates within 1 to 2 days and induces immunity within 1 to 2 months. (v) HIV supposedly causes AIDS

  4. Inducible human immunodeficiency virus type 1 packaging cell lines.

    PubMed Central

    Yu, H; Rabson, A B; Kaul, M; Ron, Y; Dougherty, J P

    1996-01-01

    Packaging cell lines are important tools for transferring genes into eukaryotic cells. Human immunodeficiency virus type 1 (HIV-1)-based packaging cell lines are difficult to obtain, in part owing to the problem that some HIV-1 proteins are cytotoxic in a variety of cells. To overcome this, we have developed an HIV-1-based packaging cell line which has an inducible expression system. The tetracycline-inducible expression system was utilized to control the expression of the Rev regulatory protein, which in turn controls the expression of the late proteins including Gag, Pol, and Env. Western blotting (immunoblotting) demonstrated that the expression of p24gag and gp120env from the packaging cells peaked on days 6 and 7 postinduction. Reverse transcriptase activity could be detected by day 4 after induction and also peaked on days 6 and 7. Defective vector virus could be propagated, yielding titers as high as 7 x 10(3) CFU/ml, while replication-competent virus was not detectable at any time. Thus, the cell line should enable the transfer of specific genes into CD4+ cells and should be a useful tool for studying the biology of HIV-1. We have also established an inducible HIV-1 Env-expressing cell line which could be used to propagate HIV-1 vectors that require only Env in trans. The env-minus vector virus titer produced from the Env-expressing cells reached 2 x 10(4) CFU/ml. The inducible HIV-1 Env-expressing cell line should be a useful tool for the study of HIV-1 Env as well. PMID:8676479

  5. Human Immunodeficiency Virus Type 1 Populations in Blood and Semen

    PubMed Central

    Delwart, Eric L.; Mullins, James I.; Gupta, Phalguni; Learn, Gerald H.; Holodniy, Mark; Katzenstein, David; Walker, Bruce D.; Singh, Mandaleshwar K.

    1998-01-01

    Transmission of human immunodeficiency virus type 1 (HIV-1) usually results in outgrowth of viruses with macrophage-tropic phenotype and consensus non-syncytium-inducing (NSI) V3 loop sequences, despite the presence of virus with broader host range and the syncytium-inducing (SI) phenotype in the blood of many donors. We examined proviruses in contemporaneous peripheral blood mononuclear cells (PBMC) and nonspermatozoal semen mononuclear cells (NSMC) of five HIV-1-infected individuals to determine if this preferential outgrowth could be due to compartmentalization and thus preferential transmission of viruses of the NSI phenotype from the male genital tract. Phylogenetic reconstructions of ∼700-bp sequences covering the second constant region through the fifth variable region (C2 to V5) of the viral envelope gene revealed distinct variant populations in the blood versus the semen in two patients with AIDS and in one asymptomatic individual (patient 613), whereas similar variant populations were found in both compartments in two other asymptomatic individuals. Variants with amino acids in the V3 loop that predict the SI phenotype were found in both AIDS patients and in patient 613; however, the distribution of these variants between the two compartments was not consistent. SI variants were found only in the PBMC of one AIDS patient but only in the NSMC of the other, while they were found in both compartments in patient 613. It is therefore unlikely that restriction of SI variants from the male genital tract accounts for the observed NSI transmission bias. Furthermore, no evidence for a semen-specific signature amino acid sequence was detected. PMID:9420266

  6. Human immunodeficiency virus type 1 populations in blood and semen.

    PubMed

    Delwart, E L; Mullins, J I; Gupta, P; Learn, G H; Holodniy, M; Katzenstein, D; Walker, B D; Singh, M K

    1998-01-01

    Transmission of human immunodeficiency virus type 1 (HIV-1) usually results in outgrowth of viruses with macrophage-tropic phenotype and consensus non-syncytium-inducing (NSI) V3 loop sequences, despite the presence of virus with broader host range and the syncytium-inducing (SI) phenotype in the blood of many donors. We examined proviruses in contemporaneous peripheral blood mononuclear cells (PBMC) and non-spermatozoal semen mononuclear cells (NSMC) of five HIV-1-infected individuals to determine if this preferential outgrowth could be due to compartmentalization and thus preferential transmission of viruses of the NSI phenotype from the male genital tract. Phylogenetic reconstructions of approximately 700-bp sequences covering the second constant region through the fifth variable region (C2 to V5) of the viral envelope gene revealed distinct variant populations in the blood versus the semen in two patients with AIDS and in one asymptomatic individual (patient 613), whereas similar variant populations were found in both compartments in two other asymptomatic individuals. Variants with amino acids in the V3 loop that predict the SI phenotype were found in both AIDS patients and in patient 613; however, the distribution of these variants between the two compartments was not consistent. SI variants were found only in the PBMC of one AIDS patient but only in the NSMC of the other, while they were found in both compartments in patient 613. It is therefore unlikely that restriction of SI variants from the male genital tract accounts for the observed NSI transmission bias. Furthermore, no evidence for a semen-specific signature amino acid sequence was detected.

  7. 76 FR 72417 - Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-23

    ... HUMAN SERVICES Centers for Disease Control and Prevention Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) Through Solid Organ Transplantation AGENCY: Centers for Disease Control and Prevention (CDC),...

  8. 76 FR 58517 - Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-21

    ... HUMAN SERVICES Centers for Disease Control and Prevention Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) Through Solid Organ Transplantation AGENCY: Centers for Disease Control and Prevention (CDC),...

  9. 75 FR 51273 - Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected Populations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-19

    ... HUMAN SERVICES Centers for Disease Control and Prevention (CDC) Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected Populations AGENCY: Centers for Disease Control and... funding available to make awards under the Centers for Disease Control and Prevention Funding...

  10. Cytoskeletal proteins inside human immunodeficiency virus type 1 virions.

    PubMed Central

    Ott, D E; Coren, L V; Kane, B P; Busch, L K; Johnson, D G; Sowder, R C; Chertova, E N; Arthur, L O; Henderson, L E

    1996-01-01

    We have identified three types of cytoskeletal proteins inside human immunodeficiency virus type 1 (HIV-1) virions by analyzing subtilisin-digested particles. HIV-1 virions were digested with protease, and the treated particles were isolated by sucrose density centrifugation. This method removes both exterior viral proteins and proteins associated with microvesicles that contaminate virion preparations. Since the proteins inside the virion are protected from digestion by the viral lipid envelope, they can be isolated and analyzed after treatment. Experiments presented here demonstrated that this procedure removed more than 95% of the protein associated with microvesicles. Proteins in digested HIV-1(MN) particles from infected H9 and CEM(ss) cell lines were analyzed by high-pressure liquid chromatography, protein sequencing, and immunoblotting. The data revealed that three types of cytoskeletal proteins are present in virions at different concentrations relative to the molar level of Gag: actin (approximately 10 to 15%), ezrin and moesin (approximately 2%), and cofilin (approximately 2 to 10%). Our analysis of proteins within virus particles detected proteolytic fragments of alpha-smooth muscle actin and moesin that were cleaved at sites which might be recognized by HIV-1 protease. These cleavage products are not present in microvesicles from uninfected cells. Therefore, these processed proteins are most probably produced by HIV-1 protease digestion. The presence of these fragments, as well as the incorporation of a few specific cytoskeletal proteins into virions, suggests an active interaction between cytoskeletal and viral proteins. PMID:8892894

  11. Role of liver transplantation in human immunodeficiency virus positive patients

    PubMed Central

    Joshi, Deepak; Agarwal, Kosh

    2015-01-01

    End-stage liver disease (ESLD) is a leading cause of morbidity and mortality amongst human immunodeficiency virus (HIV)-positive individuals. Chronic hepatitis B and hepatitis C virus (HCV) infection, drug-induced hepatotoxicity related to combined anti-retro-viral therapy, alcohol related liver disease and non-alcohol related fatty liver disease appear to be the leading causes. It is therefore, anticipated that more HIV-positive patients with ESLD will present as potential transplant candidates. HIV infection is no longer a contraindication to liver transplantation. Key transplantation outcomes such as rejection and infection rates as well as medium term graft and patient survival match those seen in the non-HIV infected patients in the absence of co-existing HCV infection. HIV disease does not seem to be negatively impacted by transplantation. However, HIV-HCV co-infection transplant outcomes remain suboptimal due to recurrence. In this article, we review the key challenges faced by this patient cohort in the pre- and post-transplant period. PMID:26604639

  12. Natural simian immunodeficiency virus transmission in mandrills: a family affair?

    PubMed Central

    Fouchet, David; Verrier, Delphine; Ngoubangoye, Barthélémy; Souquière, Sandrine; Makuwa, Maria; Kazanji, Mirdad; Gonzalez, Jean-Paul; Pontier, Dominique

    2012-01-01

    Understanding how pathogens spread and persist in the ecosystem is critical for deciphering the epidemiology of diseases of significance for global health and the fundamental mechanisms involved in the evolution of virulence and host resistance. Combining long-term behavioural and epidemiological data collected in a naturally infected mandrill population and a Bayesian framework, the present study investigated unknown aspects of the eco-epidemiology of simian immunodeficiency virus (SIV), the recent ancestor of HIV. Results show that, in contrast to what is expected from aggressive and sexual transmission (i.e. the two commonly accepted transmission modes for SIV), cases of SIVmnd-1 subtype were significantly correlated among related individuals (greater than 30% of the observed cases). Challenging the traditional view of SIV, this finding suggests the inheritance of genetic determinants of susceptibility to SIV and/or a role for behavioural interactions among maternal kin affecting the transmission of the virus, which would highlight the underappreciated role of sociality in the spread of infectious diseases. Outcomes of this study also provide novel insights into the role of host social structure in the evolution of pathogens. PMID:22673358

  13. Complementation of human immunodeficiency virus (HIV-1) gag particle formation.

    PubMed

    Zhoa, Y; Jones, I M; Hockley, D J; Nermut, M V; Roy, P

    1994-03-01

    The human immunodeficiency virus gag precursor protein Pr55Gag exhibits the ability of particle assembly when expressed using recombinant baculoviruses. In order to delineate the sequences required for particle formation, two mutants of Gag (D1 and D2) were constructed in which 10 amino acids within the CA domain were deleted. Both mutants yielded stable high levels of Gag antigen following expression in Spodoptera frugiperda insect cells. Electron microscopy of sections through infected cells revealed that neither mutant was able to assemble particles although targeting of the protein to the plasma membrane still occurred. The Gag antigen that accumulated beneath the plasma membrane exhibited distinctive morphologies when compared to each other and to parental (Pr46Gag) particles. Particle assembly was rescued when S. frugiperda cells were coinfected with both AcD1 and AcD2 viruses, or with AcD1 and a carboxyl-terminal deletion of Gag (Pr41.5) which was previously shown not to form particles (J.B.M., D.J. Hockley, M.V. Nermot, and I.M. Jones, 1992, J. Gen. Virol. 73, 3079-3086). The genetic complementation of Gag-driven assembly is discussed.

  14. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas

    PubMed Central

    Barbian, Hannah J.; Decker, Julie M.; Bibollet-Ruche, Frederic; Galimidi, Rachel P.; West, Anthony P.; Learn, Gerald H.; Parrish, Nicholas F.; Iyer, Shilpa S.; Li, Yingying; Pace, Craig S.; Song, Ruijiang; Huang, Yaoxing; Denny, Thomas N.; Mouquet, Hugo; Martin, Loic; Acharya, Priyamvada; Zhang, Baoshan; Kwong, Peter D.; Mascola, John R.; Verrips, C. Theo; Strokappe, Nika M.; Rutten, Lucy; McCoy, Laura E.; Weiss, Robin A.; Brown, Corrine S.; Jackson, Raven; Silvestri, Guido; Connors, Mark; Burton, Dennis R.; Shaw, George M.; Nussenzweig, Michel C.; Bjorkman, Pamela J.; Ho, David D.; Farzan, Michael

    2015-01-01

    ABSTRACT Broadly cross-reactive neutralizing antibodies (bNabs) represent powerful tools to combat human immunodeficiency virus type 1 (HIV-1) infection. Here, we examined whether HIV-1-specific bNabs are capable of cross-neutralizing distantly related simian immunodeficiency viruses (SIVs) infecting central (Pan troglodytes troglodytes) (SIVcpzPtt) and eastern (Pan troglodytes schweinfurthii) (SIVcpzPts) chimpanzees (n = 11) as well as western gorillas (Gorilla gorilla gorilla) (SIVgor) (n = 1). We found that bNabs directed against the CD4 binding site (n = 10), peptidoglycans at the base of variable loop 3 (V3) (n = 5), and epitopes at the interface of surface (gp120) and membrane-bound (gp41) envelope glycoproteins (n = 5) failed to neutralize SIVcpz and SIVgor strains. In addition, apex V2-directed bNabs (n = 3) as well as llama-derived (heavy chain only) antibodies (n = 6) recognizing both the CD4 binding site and gp41 epitopes were either completely inactive or neutralized only a fraction of SIVcpzPtt strains. In contrast, one antibody targeting the membrane-proximal external region (MPER) of gp41 (10E8), functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, and CD4-218.3-E51-mim2), as well as mono- and bispecific anti-human CD4 (iMab and LM52) and CCR5 (PRO140, PRO140-10E8) receptor antibodies neutralized >90% of SIVcpz and SIVgor strains with low-nanomolar (0.13 to 8.4 nM) potency. Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5 and neutralized SIVcpz in chimpanzee CD4+ T cells, with 50% inhibitory concentrations (IC50s) ranging from 3.6 to 40.5 nM. These findings provide new insight into the protective capacity of anti-HIV-1 bNabs and identify candidates for further development to combat SIVcpz infection. PMID:25900654

  15. Mutation in the primer binding site of the type 1 human immunodeficiency virus genome affects virus production and infectivity.

    PubMed Central

    Nagashunmugam, T; Velpandi, A; Goldsmith, C S; Zaki, S R; Kalyanaraman, V S; Srinivasan, A

    1992-01-01

    In an effort to understand the contribution of the primer-binding site (PBS) region to human immunodeficiency virus (HIV) replication, we have constructed a mutant HIV proviral DNA with an alteration in the 5' end of the PBS. The PBS mutant proviral DNA was characterized by transfection of the viral DNA into CD4+ and non-CD4+ target cells. The results indicate that mutation in the PBS reduced the level of viral particles released into the medium of transfected cells in comparison to wild-type proviral DNA. The viral particles were noninfectious upon transmission to established CD4+ cell lines and phytohemagglutinin-stimulated peripheral blood lymphocytes. Electron microscopic analysis of the transfected cells revealed no abnormalities in the structure of the virion directed by the mutant proviral DNA. Also, the protein and RNA contents of the mutant virions were similar to the wild type. The quantitation of intracellular viral structural protein in the transfected cells, however, indicated that the PBS mutation may have an effect on the assembly of viral particles in addition to completely abolishing reverse transcription of viral RNA into DNA. These results provide evidence that the PBS region of the viral genome has multiple functions in HIV-1 replication. Images PMID:1373895

  16. Simian Immunodeficiency Virus Infection in Wild-Caught Chimpanzees from Cameroon

    PubMed Central

    Nerrienet, Eric; Santiago, Mario L.; Foupouapouognigni, Yacouba; Bailes, Elizabeth; Mundy, Nicolas I.; Njinku, Bernadette; Kfutwah, Anfumbom; Muller-Trutwin, Michaela C.; Barre-Sinoussi, Françoise; Shaw, George M.; Sharp, Paul M.; Hahn, Beatrice H.; Ayouba, Ahidjo

    2005-01-01

    Simian immunodeficiency viruses (SIVcpz) infecting chimpanzees (Pan troglodytes) in west central Africa are the closest relatives to all major variants of human immunodeficiency virus type 1 ([HIV-1]; groups M, N and O), and have thus been implicated as the source of the human infections; however, information concerning the prevalence, geographic distribution, and subspecies association of SIVcpz still remains limited. In this study, we tested 71 wild-caught chimpanzees from Cameroon for evidence of SIVcpz infection. Thirty-nine of these were of the central subspecies (Pan troglodytes troglodytes), and 32 were of the Nigerian subspecies (Pan troglodytes vellerosus), as determined by mitochondrial DNA analysis. Serological analysis determined that one P. t. troglodytes ape (CAM13) harbored serum antibodies that cross-reacted strongly with HIV-1 antigens; all other apes were seronegative. To characterize the newly identified virus, 14 partially overlapping viral fragments were amplified from fecal virion RNA and concatenated to yield a complete SIVcpz genome (9,284 bp). Phylogenetic analyses revealed that SIVcpzCAM13 fell well within the radiation of the SIVcpzPtt group of viruses, as part of a clade including all other SIVcpzPtt strains as well as HIV-1 groups M and N. However, SIVcpzCAM13 clustered most closely with SIVcpzGAB1 from Gabon rather than with SIVcpzCAM3 and SIVcpzCAM5 from Cameroon, indicating the existence of divergent SIVcpzPtt lineages within the same geographic region. These data, together with evidence of recombination among ancestral SIVcpzPtt lineages, indicate long-standing endemic infection of central chimpanzees and reaffirm a west central African origin of HIV-1. Whether P. t. vellerosus apes are naturally infected with SIVcpz requires further study. PMID:15613358

  17. BK virus infection in human immunodeficiency virus-infected patients.

    PubMed

    Ledesma, J; Muñoz, P; Garcia de Viedma, D; Cabrero, I; Loeches, B; Montilla, P; Gijon, P; Rodriguez-Sanchez, B; Bouza, E

    2012-07-01

    The aim of this study is to evaluate the prevalence of BK virus (BKV) infection in HIV-positive patients receiving highly active antiretroviral therapy (HAART) in our hospital. The presence of BKV was analysed in urine and plasma samples from 78 non-selected HIV-infected patients. Clinical data were recorded using a pre-established protocol. We used a nested PCR to amplify a specific region of the BKV T-large antigen. Positive samples were quantified using real-time PCR. Mean CD4 count in HIV-infected patients was 472 cells/mm3 and median HIV viral load was <50 copies/mL. BKV viraemia was detected in only 1 HIV-positive patient, but 57.7% (45 out of 78) had BKV viruria, which was more common in patients with CD4 counts>500 cells/mm3 (74.3% vs 25.7%; p=0.007). Viruria was present in 21.7% of healthy controls (5 out of 23 samples, p=0.02). All viral loads were low (<100 copies/mL), and we could not find any association between BKV infection and renal or neurological manifestations. We provide an update on the prevalence of BKV in HIV-infected patients treated with HAART. BKV viruria was more common in HIV-infected patients; however, no role for BKV has been demonstrated in this population.

  18. Nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase.

    PubMed

    Sharma, Prem L; Nurpeisov, Viktoria; Hernandez-Santiago, Brenda; Beltran, Thierry; Schinazi, Raymond F

    2004-01-01

    The development of novel compounds that can effectively inhibit both wild type and the most consensus resistant strains of human immunodeficiency virus type 1 (HIV-1) is the primary focus in HIV disease management. Combination therapy, comprising at least three classes of drugs, has become the standard of care for acquired immunodeficiency syndrome (AIDS) or HIV-infected individuals. The drug cocktail can comprise all three classes of HIV inhibitors, including nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI). Due to their competitive mode of inhibition and requirement for metabolic activation, almost all NRTI drugs lack the virological potency of NNRTI or PI drugs. However, data from clinical trials indicate that sustained viral suppression could not be achieved with NRTI, NNRTI or PIs alone. Therefore, the NRTIs will remain essential components of highly active antiretroviral therapy (HAART) for the foreseeable future, because they enhance the virological potency of the regimen, they do not bind excessively to protein and most regimens are small pills/tablets given once a day. It has become apparent in recent years that the prolonged use of certain NRTIs exhibits adverse events as a class, limiting the length of time for which they can be safely used. Of major clinical concern is their association with the potentially fatal lactic acidaemia and hepatic steatosis. These class events, as well as individual drug effects, such as peripheral neuropathy, are linked to delayed mitochondrial destruction. In addition to toxicity, the development of resistance-conferring mutations against exposure to nucleoside analogs currently in use influences long-term therapeutic benefits. Of critical importance for the evaluation of new NRTIs are recent studies showing that the efficiency of discrimination or excision by pyrophosphorolysis in the presence of nucleotides of a given NRTI is a key

  19. Detection of feline immunodeficiency virus (FIV) nucleic acids in FIV-seronegative cats.

    PubMed Central

    Dandekar, S; Beebe, A M; Barlough, J; Phillips, T; Elder, J; Torten, M; Pedersen, N

    1992-01-01

    A study was undertaken to determine the rate of viral transmission among naive specific-pathogen-free (SPF) cats living in close contact with feline immunodeficiency virus (FIV)-infected cats. Twenty SPF cats were housed in the same rooms with experimentally FIV-infected seropositive and virus culture-positive cats for 2 to 4 years and were monitored for the presence of FIV nucleic acids and antibodies. Only 1 of the 20 cats became seropositive and virus culture positive and developed signs of disease. Genomic DNA from bone marrow and peripheral blood mononuclear cells (PBMC) of 10 of 19 healthy-appearing seronegative cats became positive for FIV DNA by the polymerase chain reaction. Twenty-eight SPF cats housed as groups in separate quarters and never exposed to FIV-infected cats were uniformly negative for FIV DNA. FIV RNA transcripts were detected in concanavalin A-stimulated PBMC cultures from 4 of 10 FIV DNA-positive, seronegative cats by in situ hybridization. PBMC from three of four naive SPF cats acquired FIV nucleic acids after the cats were transfused with blood and bone marrow from FIV genome-positive, seronegative donors. Three of five FIV-seronegative cats housed for years with naturally FIV-infected cats in a private household were also found to harbor FIV DNA, indicating that the same phenomenon occurred in the field. These findings demonstrate that cats living in close contact with FIV-infected seropositive cats can acquire FIV nucleic acids without developing detectable levels of serum antibodies or disease. Images PMID:1318395

  20. Seroprevalence of human herpesvirus 8 in human immunodeficiency virus 1-positive and human immunodeficiency virus 1-negative populations in Japan.

    PubMed

    Fujii, T; Taguchi, H; Katano, H; Mori, S; Nakamura, T; Nojiri, N; Nakajima, K; Tadokoro, K; Juji, T; Iwamoto, A

    1999-02-01

    To determine the seroprevalence of human herpesvirus 8 (HHV8) among human immunodeficiency virus 1 (HIV-1)-positive (HIV-1+) and HIV-1-negative (HIV-1-) populations in Japan, 276 HIV-1+ patients and 1,000 HIV-1- blood donors were enrolled in this study. Antibodies against HHV8 latency-associated nuclear antigen (LANA) were examined through indirect immunofluorescent assay by using a B-cell line that was infected latently with HHV8 (body cavity-based lymphoma 1). An HHV8- and Epstein-Barr virus-negative B-cell line (Ramos) was used as a control. Thirty-two seropositive cases against LANA (anti-LANA+) were identified among the 276 HIV-1+ patients who were studied. Five cases were foreigners living in Japan. The risk factor of all 27 Japanese cases was unprotected sexual intercourse, and the great majority of these cases (23 in 27; 85%) reported homosexual/bisexual behavior. Anti-LANA+ status correlated with the presence of sexually transmitted diseases, such as amoeba and HBV infection, further suggesting male homosexual behavior as the main route of HHV8 transmission in Japan. Only two LANA+ cases were identified among 1,000 HIV- blood donors in Japan; thus, seroprevalence of HHV8 identified by LANA was estimated to be 0.2% among HIV-1- populations in this country. PMID:9892401

  1. An inducible transcription factor activates expression of human immunodeficiency virus in T cells

    NASA Astrophysics Data System (ADS)

    Nabel, Gary; Baltimore, David

    1987-04-01

    Human immunodeficiency virus (HIV) production from latently infected T lymphocytes can be induced with compounds that activate the cells to secrete lymphokines1,2. The elements in the HIV genome which control activation are not known but expression might be regulated through a variety of DNA elements. The cis-acting control elements of the viral genome are enhancer and promoter regions. The virus also encodes trans-acting factors specified by the tat-III (refs 3-6) and art genes7. We have examined whether products specific to activated T cells might stimulate viral transcription by binding to regions on viral DNA. Activation of T cells, which increases HIV expression up to 50-fold, correlated with induction of a DNA binding protein indistinguishable from a recognized transcription factor, called NF-κB (ref. 8), with binding sites in the viral enhancer. Mutation of these binding sites abolished inducibility. That NF-κB acts in synergy with the viral tat-III gene product to enhance HIV expression in T cells may have implications for the pathogenesis of AIDS (acquired immune deficiency syndrome).

  2. Early stages of simian immunodeficiency virus infection in lymph nodes. Evidence for high viral load and successive populations of target cells.

    PubMed Central

    Chakrabarti, L.; Isola, P.; Cumont, M. C.; Claessens-Maire, M. A.; Hurtrel, M.; Montagnier, L.; Hurtrel, B.

    1994-01-01

    Lymph nodes obtained from 14 macaques sacrificed at early time points following experimental inoculation with simian immunodeficiency virus were analyzed by in situ hybridization for virus load and virus cellular tropism. The lymph nodes presented a remarkably high viral load during the early phase of infection, as viral RNA was detected in as many as 2% of lymph node cells 1 week after inoculation. At this stage, macrophages and T4 lymphocytes were identified by combined immunohistochemistry and in situ hybridization as the target cells of the virus. Simian immunodeficiency virus-positive macrophages concentrated in the subcapsular sinuses, suggesting an entry of infected cells via the afferent lymphatics. A shift in the pattern of viral infection was observed at 2 weeks after inoculation, with a concentration of viral RNA in the germinal centers of the developing lymphoid follicles. Follicular dendritic cells were found to be the major target of the virus at this stage. Follicular dendritic cells were associated with high levels of viral RNA but little or no detectable viral DNA, suggesting that the virus was present mostly in the form of viral particles trapped at the cell surface. Follicular dendritic cell-associated virus persisted at high levels for 2 months before subsiding, indicating that follicular dendritic cells constituted a major reservoir of the virus during the early stages of simian immunodeficiency virus infection. Images Figure 2 Figure 4 Figure 5 Figure 6 PMID:8203463

  3. Human immunodeficiency virus superinfection and recombination: current state of knowledge and potential clinical consequences.

    PubMed

    Blackard, Jason T; Cohen, Daniel E; Mayer, Kenneth H

    2002-04-15

    Superinfection with multiple strains or subtypes of the human and simian immunodeficiency viruses has been documented. Recent increases in the prevalences of both unprotected anal intercourse and sexually transmitted diseases among men who have sex with men indicate that these men continue to practice unsafe sex and, therefore, are at risk for superinfection with the human immunodeficiency virus (HIV). Recurrent exposure to HIV among seropositive individuals who engage in high-risk behaviors can have serious consequences, because superinfection is a necessary first step for viral recombination to occur. Recombination may produce more virulent viruses, drug-resistant viruses, or viruses with altered cell tropism. Additionally, recombinant viruses and superinfection can accelerate disease progression and increase the likelihood of sexual transmission by increasing virus load in the blood and genital tract. The extent of superinfection and recombination in persons living with HIV is unknown. The implications of HIV superinfection and the generation of recombinant viruses are discussed. PMID:11915000

  4. Role of Active and Inactive Cytotoxic Immune Response in Human Immunodeficiency Virus Dynamics

    PubMed Central

    Toro Zapata, Hernan Dario; Caicedo Casso, Angelica Graciela; Bichara, Derdei; Lee, Sunmi

    2014-01-01

    Objectives Mathematical models can be helpful to understand the complex dynamics of human immunodeficiency virus infection within a host. Most of work has studied the interactions of host responses and virus in the presence of active cytotoxic immune cells, which decay to zero when there is no virus. However, recent research highlights that cytotoxic immune cells can be inactive but never be depleted. Methods We propose a mathematical model to investigate the human immunodeficiency virus dynamics in the presence of both active and inactive cytotoxic immune cells within a host. We explore the impact of the immune responses on the dynamics of human immunodeficiency virus infection under different disease stages. Results Standard mathematical and numerical analyses are presented for this new model. Specifically, the basic reproduction number is computed and local and global stability analyses are discussed. Conclusion Our results can give helpful insights when designing more effective drug schedules in the presence of active and inactive immune responses. PMID:24955306

  5. Persistent nonproductive infection of Epstein-Barr virus-transformed human B lymphocytes by human immunodeficiency virus type 1.

    PubMed Central

    Dahl, K E; Burrage, T; Jones, F; Miller, G

    1990-01-01

    We have studied the interaction of different strains of human immunodeficiency virus type 1 (HIV-1) with an Epstein-Barr virus-transformed human B-lymphocyte line, X50-7. Previously we found that some HIV-1 strains replicated rapidly and were exclusively cytolytic; others induced persistent noncytopathic infection associated with continued shedding of extracellular virus (K. Dahl, K. Martin, and G. Miller, J. Virol. 61:1602-1608, 1987). We now describe a third form of cell-virus relationship in which infection by strain IIIB is maintained in a highly cell-associated state in a small subpopulation (less than 2%) of X50-7 cells. Neither viral subcomponents nor infectious virus was detectable in culture supernatants; however, the carrier lines were fusogenic and HIV-1 could be recovered following prolonged cocultivation with susceptible cells. In these chronic carrier cultures, virions were not seen budding at the cell surface, but a few were found within cytoplasmic vesicles. HIV-1 infection of first- and second-generation cell subclones of the carrier cell line rapidly evolved from a productive to a cell-associated state. There were low levels of HIV DNA, and RNA in the fusogenic secondary clones, but most clones lacked HIV-1 DNA, failed to express HIV-1 RNA, and exhibited no properties associated with HIV-1 infection. The experiments indicate that HIV-1 can be sequestered in human B lymphocytes. The cell cloning experiments introduce the possibility that the HIV-1 provirus may be lost from some lymphocytes. Images PMID:2157058

  6. Variability of human immunodeficiency virus-1 in the female genital reservoir during genital reactivation of herpes simplex virus type 2.

    PubMed

    LeGoff, J; Roques, P; Jenabian, M-A; Charpentier, C; Brochier, C; Bouhlal, H; Gresenguet, G; Frost, E; Pepin, J; Mayaud, P; Belec, L

    2015-09-01

    Clinical and subclinical genital herpes simplex virus type 2 (HSV-2) reactivations have been associated with increases in human immunodeficiency virus (HIV)-1 genital shedding. Whether HSV-2 shedding contributes to the selection of specific genital HIV-1 variants remains unknown. We evaluated the genetic diversity of genital and blood HIV-1 RNA and DNA in 14 HIV-1/HSV-2-co-infected women, including seven with HSV-2 genital reactivation, and seven without as controls. HIV-1 DNA and HIV-1 RNA env V1-V3 sequences in paired blood and genital samples were compared. The HSV-2 selection pressure on HIV was estimated according to the number of synonymous substitutions (dS), the number of non-synonymous substitutions (dN) and the dS/dN ratio within HIV quasi-species. HIV-1 RNA levels in cervicovaginal secretions were higher in women with HSV-2 replication than in controls (p0.02). Plasma HIV-1 RNA and genital HIV-1 RNA and DNA were genetically compartmentalized. No differences in dS, dN and the dS/dN ratio were observed between the study groups for either genital HIV-1 RNA or plasma HIV-1 RNA. In contrast, dS and dN in genital HIV-1 DNA were significantly higher in patients with HSV-2 genital reactivation (p <0.01 and p <0.05, respectively). The mean of the dS/dN ratio in genital HIV-1 DNA was slightly higher in patients with HSV-2 genital replication, indicating a trend for purifying selection (p 0.056). HSV-2 increased the genetic diversity of genital HIV-1 DNA. These observations confirm molecular interactions between HSV-2 and HIV-1 at the genital tract level. PMID:26003280

  7. Immune reconstitution syndrome in a human immunodeficiency virus infected child due to giardiasis leading to shock.

    PubMed

    Nandy, Sneha; Shah, Ira

    2015-01-01

    Human immunodeficiency virus (HIV)-associated immune reconstitution inflammatory syndrome has been reported in association with tuberculosis, herpes zoster (shingles), Cryptococcus neoformans, Kaposi's sarcoma, Pneumocystis pneumonia, hepatitis B virus, hepatitis C virus, herpes simplex virus, Histoplasma capsulatum, human papillomavirus, and Cytomegalovirus. However, it has never been documented with giardiasis. We present a 7-year-old HIV infected girl who developed diarrhea and shock following the initiation of antiretroviral therapy, and her stool showed the presence of giardiasis. PMID:26985424

  8. Modeling the Effects of Morphine on Simian Immunodeficiency Virus Dynamics

    PubMed Central

    Vaidya, Naveen K.; Ribeiro, Ruy M.; Perelson, Alan S.; Kumar, Anil

    2016-01-01

    Complications of HIV-1 infection in individuals who utilize drugs of abuse is a significant problem, because these drugs have been associated with higher virus replication and accelerated disease progression as well as severe neuropathogenesis. To gain further insight it is important to quantify the effects of drugs of abuse on HIV-1 infection dynamics. Here, we develop a mathematical model that incorporates experimentally observed effects of morphine on inducing HIV-1 co-receptor expression. For comparison we also considered viral dynamic models with cytolytic or noncytolytic effector cell responses. Based on the small sample size Akaike information criterion, these models were inferior to the new model based on changes in co-receptor expression. The model with morphine affecting co-receptor expression agrees well with the experimental data from simian immunodeficiency virus infections in morphine-addicted macaques. Our results show that morphine promotes a target cell subpopulation switch from a lower level of susceptibility to a state that is about 2-orders of magnitude higher in susceptibility to SIV infection. As a result, the proportion of target cells with higher susceptibility remains extremely high in morphine conditioning. Such a morphine-induced population switch not only has adverse effects on the replication rate, but also results in a higher steady state viral load and larger CD4 count drops. Moreover, morphine conditioning may pose extra obstacles to controlling viral load during antiretroviral therapy, such as pre-exposure prophylaxis and post infection treatments. This study provides, for the first time, a viral dynamics model, viral dynamics parameters, and related analytical and simulation results for SIV dynamics under drugs of abuse. PMID:27668463

  9. [Antiretroviral therapy in human immunodeficiency virus infection: an update].

    PubMed

    Chaix, F; Goujard, C

    2009-06-01

    Since the onset of the human immunodeficiency virus (HIV) epidemic, the care of infected patients improved dramatically. Whereas the disease was almost always fatal, the development of new drugs and new therapeutic strategies now allow a prolonged survival. However, the complexity of patient care is increasing and physicians face new clinical events and treatment toxicities. Recent molecules and follow-up according to the recent French recommendations will be presented here. The objectives of the treatment is to decrease mortality and morbidity of the HIV infection, by restoring near normal CD4+ T cell counts and qualitative T CD4+ responses, associated with a sustained reduction in viral replication. This objective must be reached by minimizing toxicity of antiretroviral drugs. Newly developed drugs that are better-tolerated and new therapeutic classes should improve outcome at all stages of HIV infection. Whereas viral eradication remains unrealistic and protective vaccines will not be soon available, direct consequences of long term HIV infection and issues related to an ageing HIV infected population raise up new research topics. Prevention of new infections, improvement in the precocity of care by a better-targeted screening and assessment of therapy before an established immune deficiency appear as the main priorities for the coming years. PMID:19237230

  10. Tuberculous meningitis in patients infected with human immunodeficiency virus.

    PubMed

    Garg, Ravindra Kumar; Sinha, Manish Kumar

    2011-01-01

    Tuberculosis is the most common opportunistic infection in human immunodeficiency virus (HIV) infected persons. HIV-infected patients have a high incidence of tuberculous meningitis as well. The exact incidence and prevalence of tuberculous meningitis in HIV-infected patients are not known. HIV infection does not significantly alter the clinical manifestations, laboratory, radiographic findings, or the response to therapy. Still, some differences have been noted. For example, the histopathological examination of exudates in HIV-infected patients shows fewer lymphocytes, epithelioid cells, and Langhan's type of giant cells. Larger numbers of acid-fast bacilli may be seen in the cerebral parenchyma and meninges. The chest radiograph is abnormal in up to 46% of patients with tuberculous meningitis. Tuberculous meningitis is likely to present with cerebral infarcts and mass lesions. Cryptococcal meningitis is important in differential diagnosis. The recommended duration of treatment in HIV-infected patients is 9-12 months. The benefit of adjunctive corticosteroids is uncertain. Antiretroviral therapy and antituberculosis treatment should be initiated at the same time, regardless of CD4 cell counts. Tuberculous meningitis may be a manifestation of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. Some studies have demonstrated a significant impact of HIV co-infection on mortality from tuberculous meningitis. HIV-infected patients with multidrug-resistant tuberculous meningitis have significantly higher mortality. The best way to prevent HIV-associated tuberculous meningitis is to diagnose and isolate infectious cases of tuberculosis promptly and administer appropriate treatment.

  11. Stability of the gorilla microbiome despite simian immunodeficiency virus infection.

    PubMed

    Moeller, Andrew H; Peeters, Martine; Ayouba, Ahidjo; Ngole, Eitel Mpoudi; Esteban, Amadine; Hahn, Beatrice H; Ochman, Howard

    2015-02-01

    Simian immunodeficiency viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in faecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. Here, we examine the effects of SIVgor, a close relative of SIVcpz of chimpanzees and HIV-1 of humans, on the gut bacterial communities residing within wild gorillas, revealing that gorilla gut microbiomes are exceptionally robust to SIV infection. In contrast to the microbiomes of HIV-1-infected humans and SIVcpz-infected chimpanzees, SIVgor-infected gorilla microbiomes exhibit neither rises in the frequencies of opportunistic pathogens nor elevated rates of microbial turnover within individual hosts. Regardless of SIV infection status, gorilla microbiomes assort into enterotypes, one of which is compositionally analogous to those identified in humans and chimpanzees. The other gorilla enterotype appears specialized for a leaf-based diet and is enriched in environmentally derived bacterial genera. We hypothesize that the acquisition of this gorilla-specific enterotype was enabled by lowered immune system control over the composition of the microbiome. Our results indicate differences between the pathology of SIVgor and SIVcpz/HIV-1 infections, demonstrating the utility of investigating host microbial ecology as a means for studying disease in wild primates of high conservation priority.

  12. Testicular dysfunction in human immunodeficiency virus-infected men.

    PubMed

    Poretsky, L; Can, S; Zumoff, B

    1995-07-01

    This review pertains to gonadal function in men with human immunodeficiency virus (HIV) infection, who often exhibit clinical and biochemical evidence of hypogonadism. Hypogonadotropic hypogonadism appears to be the most commonly encountered abnormality, although complete anterior pituitary insufficiency and primary gonadal failure have been reported. Levels of sex hormone-binding globulin (SHBG) are either unchanged or increased. Plasma levels of estrogens, progesterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), and prolactin vary. Pathologically, except for involvement by opportunistic infections, no significant abnormality in the hypothalamic-pituitary area has been described, but evidence of orchitis is commonly present. The cause(s) of these abnormalities remains unclear. The possible factors leading to hypogonadism in HIV-infected men include HIV infection itself, opportunistic infections, chronic debilitating illness, and effects of cytokines on the hypothalamic-pituitary-gonadal axis. Further studies are needed to clarify the cause(s) of testicular dysfunction in HIV-infected men and its clinical significance, treatment, relevance to the progression of HIV infection, and influence on the immune system.

  13. Selective destruction of cells infected with human immunodeficiency virus

    DOEpatents

    Keener, William K.; Ward, Thomas E.

    2003-09-30

    Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a variant of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

  14. Selective Destruction Of Cells Infected With The Human Immunodeficiency Virus

    DOEpatents

    Keener, William K.; Ward, Thomas E.

    2006-03-28

    Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a varient of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

  15. Hepatitis B and human immunodeficiency virus co-infection

    PubMed Central

    Phung, Bao-Chau; Sogni, Philippe; Launay, Odile

    2014-01-01

    Hepatitis B and human immunodeficiency virus (HBV and HIV) infection share transmission patterns and risk factors, which explains high prevalence of chronic HBV infection in HIV infected patients. The natural course of HBV disease is altered by the HIV infection with less chance to clear acute HBV infection, faster progression to cirrhosis and higher risk of liver-related death in HIV-HBV co-infected patients than in HBV mono-infected ones. HIV infected patients with chronic hepatitis B should be counseled for liver damage and surveillance of chronic hepatitis B should be performed to screen early hepatocellular carcinoma. Noninvasive tools are now available to evaluate liver fibrosis. Isolated hepatitis B core antibodies (anti-HBc) are a good predictive marker of occult HBV infection. Still the prevalence and significance of occult HBV infection is controversial, but its screening may be important in the management of antiretroviral therapy. Vaccination against HBV infection is recommended in non-immune HIV patients. The optimal treatment for almost all HIV-HBV co-infected patients should contain tenofovir plus lamivudine or emtricitabine and treatment should not be stopped to avoid HBV reactivation. Long term tenofovir therapy may lead to significant decline in hepatitis B surface Antigen. The emergence of resistant HBV strains may compromise the HBV therapy and vaccine therapy. PMID:25516647

  16. Update on kidney transplantation in human immunodeficiency virus infected recipients.

    PubMed

    Nashar, Khaled; Sureshkumar, Kalathil K

    2016-07-01

    Improved survival of human immunodeficiency virus (HIV) infected patients with chronic kidney disease following the introduction of antiretroviral therapy resulted in the need to revisit the topic of kidney transplantation in these patients. Large cohort studies have demonstrated favorable outcomes and proved that transplantation is a viable therapeutic option. However, HIV-infected recipients had higher rates of rejection. Immunosuppressive therapy did not negatively impact the course of HIV infection. Some of the immunosuppressive drugs used following transplantation exhibit antiretroviral effects. A close collaboration between infectious disease specialists and transplant professionals is mandatory in order to optimize transplantation outcomes in these patients. Transplantation from HIV(+) donors to HIV(+) recipients has been a subject of intense debate. The HIV Organ Policy Equity act provided a platform to research this area further and to develop guidelines. The first HIV(+) to HIV(+) kidney transplant in the United States and the first HIV(+) to HIV(+) liver transplant in the world were recently performed at the Johns Hopkins University Medical Center. PMID:27458559

  17. Inhibition of productive human immunodeficiency virus-1 infection by cobalamins.

    PubMed

    Weinberg, J B; Sauls, D L; Misukonis, M A; Shugars, D C

    1995-08-15

    Various cobalamins act as important enzyme cofactors and modulate cellular function. We investigated cobalamins for their abilities to modify productive human immunodeficiency virus-1 (HIV-1) infection of hematopoietic cells in vitro. We show that hydroxocobalamin (OH-Cbl), methylcobalamin (Me-Cbl), and adenosylcobalamin Ado-Cbl (Ado-Cbl) inhibit HIV-1 infection of normal human blood monocytes and lymphocytes. The inhibitory effects were noted when analyzing the monocytotropic strains HIV-1-BaL and HIV-1-ADA as well as the lymphocytotropic strain HIV-1-LAI. Cobalamins did not modify binding of gp120 to CD4 or block early steps in viral life cycle, inhibit reverse transcriptase, inhibit induction of HIV-1 expression from cells with established or latent infection, or modify monocyte interferon-alpha production. Because of the ability to achieve high blood and tissue levels of cobalamins in vivo and the general lack of toxicity, cobalamins should be considered as potentially useful agents for the treatment of HIV-1 infection. PMID:7632933

  18. Recombination increases human immunodeficiency virus fitness, but not necessarily diversity.

    PubMed

    Vijay, N N V; Vasantika; Ajmani, Rahul; Perelson, Alan S; Dixit, Narendra M

    2008-06-01

    Recombination can facilitate the accumulation of mutations and accelerate the emergence of resistance to current antiretroviral therapies for human immunodeficiency virus (HIV) infection. Yet, since recombination can also dissociate favourable combinations of mutations, the benefit of recombination to HIV remains in question. The confounding effects of mutation, multiple infections of cells, random genetic drift and fitness selection that underlie HIV evolution render the influence of recombination difficult to unravel. We developed computer simulations that mimic the genomic diversification of HIV within an infected individual and elucidate the influence of recombination. We find, interestingly, that when the effective population size of HIV is small, recombination increases both the diversity and the mean fitness of the viral population. When the effective population size is large, recombination increases viral fitness but decreases diversity. In effect, recombination enhances (lowers) the likelihood of the existence of multi-drug resistant strains of HIV in infected individuals prior to the onset of therapy when the effective population size is small (large). Our simulations are consistent with several recent experimental observations, including the evolution of HIV diversity and divergence in vivo. The intriguing dependencies on the effective population size appear due to the subtle interplay of drift, selection and epistasis, which we discuss in the light of modern population genetics theories. Current estimates of the effective population size of HIV have large discrepancies. Our simulations present an avenue for accurate determination of the effective population size of HIV in vivo and facilitate establishment of the benefit of recombination to HIV.

  19. Syphilis, leprosy, and human immunodeficiency virus coinfection: a challenging diagnosis.

    PubMed

    Souza, Claudia Fd; Bornhausen-Demarch, Eduardo; Prata, Aline G; de Andrade, Felipe C; Fernandes, Mariana P; Lopes, Marcia Ra; Nery, José Ac

    2013-08-01

    The association between syphilis, leprosy, and human immunodeficiency virus (HIV) is not well documented, and the emergence of isolated cases raises the interest and indicates that this triple coinfection can occur. We report the case of a 42-year-old man from Rio de Janeiro, Brazil, who presented with erythematous papules on the trunk, back, and upper and lower extremities; an erythematous plaque on the upper abdomen; and an erythematous violaceous plaque on the right thigh with altered sensitivity. Laboratory investigation showed a reagent VDRL test (1:512) and positive test results for Treponema pallidum hemagglutination. Treatment with benzathine penicillin (2,400,000 U intramuscularly) was started (2 doses 1 week apart). On follow-up 40 days later, the lesions showed partial improvement with persistence of the plaques on the right thigh and upper abdomen as well as a new similar plaque on the back. Further laboratory examinations showed negative bacilloscopy, positive HIV test, and histologic findings consistent with tuberculoid leprosy. The patient was started on multidrug therapy for paucibacillary leprosy with clinical improvement; the patient also was monitored by the HIV/AIDS department. We emphasize the importance of clinical suspicion for a coinfection case despite the polymorphism of these diseases as well as the precise interpretation of laboratory and histopathology examinations to correctly manage atypical cases. PMID:24087779

  20. Update on kidney transplantation in human immunodeficiency virus infected recipients

    PubMed Central

    Nashar, Khaled; Sureshkumar, Kalathil K

    2016-01-01

    Improved survival of human immunodeficiency virus (HIV) infected patients with chronic kidney disease following the introduction of antiretroviral therapy resulted in the need to revisit the topic of kidney transplantation in these patients. Large cohort studies have demonstrated favorable outcomes and proved that transplantation is a viable therapeutic option. However, HIV-infected recipients had higher rates of rejection. Immunosuppressive therapy did not negatively impact the course of HIV infection. Some of the immunosuppressive drugs used following transplantation exhibit antiretroviral effects. A close collaboration between infectious disease specialists and transplant professionals is mandatory in order to optimize transplantation outcomes in these patients. Transplantation from HIV+ donors to HIV+ recipients has been a subject of intense debate. The HIV Organ Policy Equity act provided a platform to research this area further and to develop guidelines. The first HIV+ to HIV+ kidney transplant in the United States and the first HIV+ to HIV+ liver transplant in the world were recently performed at the Johns Hopkins University Medical Center. PMID:27458559

  1. Markers predicting progression of human immunodeficiency virus-related disease.

    PubMed Central

    Tsoukas, C M; Bernard, N F

    1994-01-01

    Human immunodeficiency virus (HIV) interacts with the immune system throughout the course of infection. For most of the disease process, HIV activates the immune system, and the degree of activation can be assessed by measuring serum levels of molecules such as beta 2-microglobulin and neopterin, as well as other serum and cell surface phenotype markers. The levels of some of these markers correlate with clinical progression of HIV disease, and these markers may be useful as surrogate markers for development of clinical AIDS. Because the likelihood and timing of development of clinical AIDS following seroconversion, for any particular individual, are not readily predictable, the use of nonclinical disease markers has become critically important to patient management. Surrogate markers of HIV infection are, by definition, measurable traits that correlate with disease progression. An ideal marker should identify patients at highest risk of disease progression, provide information on how long an individual has been infected, help in staging HIV disease, predict development of opportunistic infections associated with AIDS, monitor the therapeutic efficacy of immunomodulating or antiviral treatments, and the easily quantifiable, reliable, clinically available, and affordable. This review examines the current state of knowledge and the role of surrogate markers in the natural history and treatment of HIV infection. The clinical usefulness of each marker is assessed with respect to the criteria outlined for the ideal surrogate marker for HIV disease progression. PMID:8118788

  2. Human immunodeficiency virus type 1 infection of the brain.

    PubMed Central

    Atwood, W J; Berger, J R; Kaderman, R; Tornatore, C S; Major, E O

    1993-01-01

    Direct infection of the central nervous system by human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, was not appreciated in the early years of the AIDS epidemic. Neurological complications associated with AIDS were largely attributed to opportunistic infections that arose as a result of the immunocompromised state of the patient and to depression. In 1985, several groups succeeded in isolating HIV-1 directly from brain tissue. Also that year, the viral genome was completely sequenced, and HIV-1 was found to belong to a neurotropic subfamily of retrovirus known as the Lentivirinae. These findings clearly indicated that direct HIV-1 infection of the central nervous system played a role in the development of AIDS-related neurological disease. This review summarizes the clinical manifestations of HIV-1 infection of the central nervous system and the related neuropathology, the tropism of HIV-1 for specific cell types both within and outside of the nervous system, the possible mechanisms by which HIV-1 damages the nervous system, and the current strategies for diagnosis and treatment of HIV-1-associated neuropathology. Images PMID:8269391

  3. Exercise dysfunction in patients seropositive for the human immunodeficiency virus

    SciTech Connect

    Johnson, J.E.; Anders, G.T.; Blanton, H.M.; Hawkes, C.E.; Bush, B.A.; McAllister, C.K.; Matthews, J.I. )

    1990-03-01

    To confirm the presence of exercise dysfunction in patients seropositive for the human immunodeficiency virus (HIV), 32 such patients without AIDS were evaluated with cardiopulmonary exercise testing, pulmonary function testing, bronchoalveolar lavage, chest roentgenography, and gallium scanning. No evidence of pulmonary opportunistic infection was found. When compared to an otherwise similar group of HIV-seronegative controls, the patients exercised to a significantly lower workload (195 +/- 30 versus 227 +/- 31 W, p less than 0.001). The ventilatory anaerobic threshold (VAT) values were also significantly lower for the patients (49.2 +/- 13.0 versus 61.9 +/- 9.1% of maximum predicted VO2, p less than 0.001). Nine of the patients had VAT values less than the 95% confidence interval for the controls. This subgroup exercised to a significantly lower maximum VO2 (69.9 +/- 11.2 versus 95.9 +/- 17.5% of maximum predicted VO2, p less than 0.001) and workload (165 +/- 21 versus 227 +/- 31 W) when compared to the control group. These patients demonstrated a mild tachypnea throughout exercise relative to the controls and had a significant increase in the slope of the heart rate to VO2 relationship. These findings are most consistent with a limitation of oxygen delivery to exercising muscles, which may represent occult cardiac disease in this group.

  4. Real-Time PCR Assay for Clinical Management of Human Immunodeficiency Virus-Infected Patients with Visceral Leishmaniasis

    PubMed Central

    Bossolasco, Simona; Gaiera, Giovanni; Olchini, Davide; Gulletta, Maurizio; Martello, Leonardo; Bestetti, Arabella; Bossi, Laura; Germagnoli, Luca; Lazzarin, Adriano; Uberti-Foppa, Caterina; Cinque, Paola

    2003-01-01

    To evaluate the usefulness of a real-time PCR for Leishmania DNA in the diagnosis and follow-up of patients with human immunodeficiency virus type 1 (HIV-1) and Leishmania coinfection, Leishmania DNA levels were measured in whole peripheral blood from 25 HIV-infected patients with clinical features suggestive of visceral leishmaniasis. Leishmania DNA was detected in 10 of 25 patients with microscopically confirmed visceral leishmaniasis and in none of those without this disease. Following treatment with liposomal amphotericin B, a clinical response was observed in 9 of 10 patients, in association with significantly decreased parasite loads. Seven patients relapsed clinically a median of 110 days after the end of treatment, in association with substantial increases in Leishmania DNA levels. Leishmania DNA levels correlated with the clinical course of visceral leishmaniasis, and their measurement at diagnosis and during and after treatment seems to be useful in the clinical management of HIV-infected patients with this disease. PMID:14605142

  5. Generation of hybrid human immunodeficiency virus utilizing the cotransfection method and analysis of cellular tropism.

    PubMed Central

    Velpandi, A; Nagashunmugam, T; Murthy, S; Cartas, M; Monken, C; Srinivasan, A

    1991-01-01

    Human immunodeficiency viruses (HIV) isolated from infected individuals show tremendous genetic and biologic diversity. To delineate the genetic determinants underlying specific biologic characteristics, such as rate of replication, cytopathic effects, and ability to infect macrophages and T4 lymphoid cells, generation of hybrid HIV using viruses which exhibit distinct biologic features is essential. To develop methods for generating hybrid HIV, we constructed truncated HIV proviral DNA plasmids. Upon digestion with restriction enzymes, these plasmid DNAs were cotransfected into human rhabdomyosarcoma cells to generate hybrid HIV. The hybrid HIVs derived by this method were infectious upon transmission to both phytohemagglutinin-stimulated peripheral blood lymphocytes and established human leukemic T-cell lines. The virus derived from molecular clone pHXB2 (HIVHTLV-III) productively infected CEMx174 cells. On the other hand, molecular clone pARV (HIVSF2)-derived virus did not show productive infection of CEMx174 cells when used as a cell-free virus. The hybrid HIV containing the 3' end of the genome from pARV and the 5' end of the genome from pHXB2 was effective in infecting CEMx174 cells, but the converse hybrid containing 5' pARV and 3' pHXB2 was not effective in infecting CEMx174 cells. These results suggest that differences in the genes outside of env and nef play a role in the ability of the virus to infect a certain cell type. The intracellular ligation method should be useful in the analysis of related and unrelated HIV-1 isolates with common restriction enzyme cleavage sites. Images PMID:1678438

  6. Generation of hybrid human immunodeficiency virus utilizing the cotransfection method and analysis of cellular tropism.

    PubMed

    Velpandi, A; Nagashunmugam, T; Murthy, S; Cartas, M; Monken, C; Srinivasan, A

    1991-09-01

    Human immunodeficiency viruses (HIV) isolated from infected individuals show tremendous genetic and biologic diversity. To delineate the genetic determinants underlying specific biologic characteristics, such as rate of replication, cytopathic effects, and ability to infect macrophages and T4 lymphoid cells, generation of hybrid HIV using viruses which exhibit distinct biologic features is essential. To develop methods for generating hybrid HIV, we constructed truncated HIV proviral DNA plasmids. Upon digestion with restriction enzymes, these plasmid DNAs were cotransfected into human rhabdomyosarcoma cells to generate hybrid HIV. The hybrid HIVs derived by this method were infectious upon transmission to both phytohemagglutinin-stimulated peripheral blood lymphocytes and established human leukemic T-cell lines. The virus derived from molecular clone pHXB2 (HIVHTLV-III) productively infected CEMx174 cells. On the other hand, molecular clone pARV (HIVSF2)-derived virus did not show productive infection of CEMx174 cells when used as a cell-free virus. The hybrid HIV containing the 3' end of the genome from pARV and the 5' end of the genome from pHXB2 was effective in infecting CEMx174 cells, but the converse hybrid containing 5' pARV and 3' pHXB2 was not effective in infecting CEMx174 cells. These results suggest that differences in the genes outside of env and nef play a role in the ability of the virus to infect a certain cell type. The intracellular ligation method should be useful in the analysis of related and unrelated HIV-1 isolates with common restriction enzyme cleavage sites.

  7. Five recombinant simian immunodeficiency virus pseudotypes lead to exclusive transduction of retinal pigmented epithelium in rat.

    PubMed

    Duisit, Ghislaine; Conrath, Hervé; Saleun, Sylvie; Folliot, Sebastien; Provost, Nathalie; Cosset, François-Loïc; Sandrin, Virginie; Moullier, Philippe; Rolling, Fabienne

    2002-10-01

    The purpose of our study was to evaluate lentiviral vector-mediated rat retinal transduction using simian immunodeficiency virus (SIV) pseudotyped with envelope proteins from vesicular stomatitis virus G glycoprotein (VSV-G), Mokola virus G protein (MK-G), amphotropic murine leukemia virus envelope (4070A-Env), influenza A virus hemagglutinin (HA), lymphocytic choriomeningitis virus G protein (LCMV-G), and RD114 retrovirus envelope (RD114-Env). The six pseudotyped lentivirus vectors carried CMV-driven green fluorescent protein (GFP) or beta-galactosidase (beta-gal) reporter genes. Intravitreal and subretinal injections of each pseudotyped recombinant SIV were performed in cohorts of Wistar rats. Our results showed that no transgene expression was detected after intravitreal injection of each pseudotyped SIV vector. Also, no transduction could be detected following subretinal injection of RD114 pseudotyped SIV vectors. However, selective transduction of retinal pigment epithelium (RPE) cells was repeatedly obtained after subretinal delivery of VSV-G, MK-G, 4070A-Env, HA, and LCMV-G pseudotyped SIV. GFP expression was maximum as soon as 4 days postadministration for VSV-G, MK-G, 4070A-Env, and HA pseudotypes, with no evidence of pseudotransduction for VSV-G. Maximum transgene expression was observed 3 weeks postinjection for LCMV-6. Importantly, HA and VSV-G pseudotyped SIV lead to such a high level of transgene expression that GFP-related toxicity occurred. Therefore, when a high level of GFP synthesis is achieved, replacement of enhanced GFP (egfp, Aequorea victoria) by a low-toxicity GFP (Renilla reniformis) cDNA is necessary to allow long-term expression.

  8. Characterization of multiple mRNA species of simian immunodeficiency virus from macaques in a CD4+ lymphoid cell line.

    PubMed Central

    Park, I W; Steen, R; Li, Y

    1991-01-01

    Cytoplasmic poly(A)+ RNA was isolated from CEMX721.174 cells 5 to 10 days after infection with molecularly cloned simian immunodeficiency virus SIVmac239. Expression of SIV RNA was analyzed by Northern (RNA) blot hybridization and by sequencing of cDNA clones. As expected, a splice donor site was demonstrated in the untranslated leader sequence outside the left long terminal repeat. The region between pol and env was found to contain at least two splice donor and six splice acceptor sites. Splice acceptor and donor sites in the intergenic region were suitably positioned for expression of vpx, vpr, tat, and rev. Splice acceptor sites at nucleotides 8802 and 8805 were demonstrated in singly and doubly spliced RNAs with the potential of expressing nef and the second exons of tat and rev. Our results demonstrate a complex pattern of alternative splicing of SIV mRNAs. The results are very similar to what has been observed in human immunodeficiency virus type 1-infected cells, suggesting that both human and simian immunodeficiency viruses are subject to multiple levels of regulation. Images PMID:1674547

  9. Seroprevalence of feline leukemia virus and feline immunodeficiency virus infection among cats in Canada

    PubMed Central

    Little, Susan; Sears, William; Lachtara, Jessica; Bienzle, Dorothee

    2009-01-01

    The purposes of this study were to determine the seroprevalence of feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) infection among cats in Canada and to identify risk factors for seropositivity. Signalment, lifestyle factors, and test results for FeLV antigen and FIV antibody were analyzed for 11 144 cats from the 10 Canadian provinces. Seroprevalence for FIV antibody was 4.3% and seroprevalence for FeLV antigen was 3.4%. Fifty-eight cats (0.5%) were seropositive for both viruses. Seroprevalence varied geographically. Factors such as age, gender, health status, and lifestyle were significantly associated with risk of FeLV and FIV seropositivity. The results suggest that cats in Canada are at risk of retrovirus infection and support current recommendations that the retrovirus status of all cats should be known. PMID:19721785

  10. In vivo pathogenic properties of two clonal human immunodeficiency virus type 1 isolates.

    PubMed Central

    Jamieson, B D; Pang, S; Aldrovandi, G M; Zha, J; Zack, J A

    1995-01-01

    We have investigated the in vivo pathogenic properties of two molecularly cloned strains of human immunodeficiency virus type 1 (HIV-1), HIV-1NL4-3 and HIV-1JR-CSF, in human fetal thymus/liver implants in severe combined immunodeficient mice. Studies comparing their in vivo replication kinetics and abilities to induce CD4+ thymocyte depletion were performed. HIV-1NL4-3 replicated in vivo with faster kinetics and induced greater levels of CD4+ thymocyte depletion than did HIV-1JR-CSF. These results demonstrate that different viral isolates have different pathogenic properties in this system. In the SCID-hu model, this pathogenesis most likely occurs in the absence of an immune response. Therefore, we investigated whether the absence of immune selection resulted in extensive genetic variation and the generation of viral quasispecies. To this end, DNA corresponding to the fourth variable domain region of the viral envelope gp120 protein recovered from biopsy samples at 6 weeks postinfection was sequenced. Little genetic variation was noted in either HIV-1JR-CSF- or HIV-1NL4-3-infected implants. The mutation levels demonstrated in both viral strains were more reflective of the acute rather than the chronic phase of HIV-1 infection in humans. These results suggest that the SCID-hu mouse model can be used to study the in vivo pathogenicity of different HIV-1 isolates in the absence of host immune selective pressures. PMID:7666526

  11. Simian virus 40-induced disease in rhesus monkeys with simian acquired immunodeficiency syndrome.

    PubMed Central

    Horvath, C. J.; Simon, M. A.; Bergsagel, D. J.; Pauley, D. R.; King, N. W.; Garcea, R. L.; Ringler, D. J.

    1992-01-01

    Simian virus 40 (SV40) disease was diagnosed in four rhesus monkeys that died with SIV-induced acquired immunodeficiency syndrome (AIDS). One juvenile monkey seroconverted for SV40 6 months after inoculation with SIV and developed severe bilateral tubulointerstitial nephritis. In contrast, progressive multifocal leukoencephalopathy (PML) occurred in two adult monkeys that were seropositive for SV40 before SIV inoculation, as well as a third adult that was naturally infected with SIV and seropositive for SV40 5 years before death. Large intranuclear inclusions containing abundant polyomavirus particles were limited to either renal tubular epithelial cells or oligodendrocytes. In situ DNA hybridization for SV40 large T antigen further demonstrated that SV40 nucleic acid was localized to either kidney or brain tissue. By immunohistochemical analysis, areas of central nervous system inflammation and demyelination were shown to contain CD68+ macrophages (gitter cells), aggregates of CD8+ T lymphocytes, and numerous gemistocytic astrocytes that labeled for glial fibrillary acidic protein. These observations indicate that rhesus monkeys with SIV-induced AIDS are predisposed to polyomaviral disease, in which SV40 nucleic acid is observed in renal tissue in primary infections and brain tissue after viral reactivation. Furthermore, this organ-specific replication suggests that tissue-tropic strains of SV40 may develop in immunodeficient monkeys. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1376560

  12. Effects of long terminal repeat mutations on human immunodeficiency virus type 1 replication.

    PubMed Central

    Lu, Y; Stenzel, M; Sodroski, J G; Haseltine, W A

    1989-01-01

    The effects of deletions within three functional regions of the long terminal repeat of human immunodeficiency virus type 1 upon the ability of the long terminal repeat to direct production of the chloramphenicol acetyltransferase gene product and upon the ability of viruses that carry the mutations to replicate in human cell lines was investigated. The results show that the enhancer and TATAA sequences were required for efficient virus replication. Deletion of the negative regulatory element (NRE) yielded a virus that replicated more rapidly than did an otherwise isogeneic NRE-positive virus. The suppressive effect of the NRE did not depend upon the negative regulatory gene (nef), as both NRE-positive and NRE-negative viruses were defective for nef. We conclude that factors specified by the cell interact with the NRE sequences to retard human immunodeficiency virus type 1 replication. PMID:2760991

  13. Human immunodeficiency virus type 1 replication within cystic lymphoepithelial lesion of the salivary gland.

    PubMed

    Labouyrie, E; Merlio, J P; Beylot-Barry, M; Delord, B; Vergier, B; Brossard, G; Lacoste, D; Beylot, J; Leng, B; Fleury, H

    1993-07-01

    Cystic lymphoepithelial lesions of salivary glands (CLLSG) are nodular or diffuse salivary gland enlargements that are observed in patients who tested positive for human immunodeficiency virus type 1 (HIV-1). Two cases of CLLSG are reported. Particular emphasis is placed on the presence of HIV-1 major-core protein (P24), HIV-1 RNA sequences, Epstein-Barr virus (EBV) DNA sequences, and lymphocyte receptor gene rearrangement. Lymphoid alterations consisted of explosive hyperplasia with a prominent follicular reticular dendritic cell (DRC) network and numerous intrafollicular CD8+ lymphocytes. Intrafollicular DRC strongly expressed HIV-1 major-core protein and HIV-1 RNA, indicating that most DRCs actively replicated the HIV-1 virus. The presence of active HIV-1 replication within DRC and the absence of clonal EBV infected lymphoid population strongly suggest that CLLSG pathogenesis is primarily induced by HIV-1. The presence of oligoclonal immunoglobulin gene rearrangements in our cases, however, suggest the need of long-term follow-up of such patients to determine whether CLLSG could be a benign prelymphomatous disease.

  14. Specific proliferative T cell responses and antibodies elicited by vaccination with simian immunodeficiency virus Nef do not confer protection against virus challenge.

    PubMed

    Wade-Evans, A M; Stott, J; Hanke, T; Stebbings, R; Berry, N; Lines, J; Sangster, R; Silvera, P; Walker, B; MacManus, S; Davis, G; Cowie, J; Arnold, C; Hull, R; Almond, N

    2001-11-01

    The efficacy of immunizing with a combination of simian immunodeficiency virus (SIV) Nef vaccines was evaluated. Four vaccinates received three intradermal immunizations with recombinant vaccinia virus that expressed SIV Nef, followed by three intramuscular immunizations with rDNA also expressing SIV Nef. Finally, the four vaccinates received two subcutaneous boosts with recombinant SIV Nef protein. This immunization protocol elicited anti-Nef antibodies in all of the vaccinates as well as specific proliferative responses. However, specific cytotoxic T cell responses were not detected before virus challenge. All vaccinates were challenged intravenously with 10 MID(50) of SIVmacJ5 along with four controls. All eight subjects became infected after SIV challenge and there were no group-specific differences in virus load as measured by virus titration and vRNA analysis. The results of this study support indirectly the report from Gallimore and colleagues (Nat Med 1995;1:1667) suggesting that CD8(+) T lymphocyte responses are required for Nef-based vaccines to restrict SIV infection. If Nef-based vaccines are to be beneficial in controlling infection with immunodeficiency viruses, then it will be necessary to develop more effective immunization protocols that elicit potent CD8(+) cell responses reproducibly.

  15. Role of Vif in Stability of the Human Immunodeficiency Virus Type 1 Core

    PubMed Central

    Öhagen, Åsa; Gabuzda, Dana

    2000-01-01

    The Vif protein of human immunodeficiency virus type 1 (HIV-1) is important for virion infectivity. Previous studies have shown that vif-defective virions exhibit structural abnormalities in the virus core and are defective in the ability to complete proviral DNA synthesis in acutely infected cells. We developed novel assays to assess the relative stability of the core in HIV-1 virions. Using these assays, we examined the role of Vif in the stability of the HIV-1 core. The integrity of the core was examined following virion permeabilization or removal of the lipid envelope and treatment with various triggers, including S100 cytosol, deoxynucleoside triphosphates, detergents, NaCl, and buffers of different pH to mimic aspects of the uncoating and disassembly process which occurs after virus entry but preceding or during reverse transcription. vif mutant cores were more sensitive to disruption by all triggers tested than wild-type cores, as determined by endogenous reverse transcriptase (RT) assays, biochemical analyses, and electron microscopy. RT and the p7 nucleocapsid protein were released more readily from vif mutant virions than from wild-type virions, suggesting that the internal nucleocapsid is less stably packaged in the absence of Vif. Purified cores could be isolated from wild-type but not vif mutant virions by sedimentation through detergent-treated gradients. These results demonstrate that Vif increases the stability of virion cores. This may permit efficient viral DNA synthesis by preventing premature degradation or disassembly of viral nucleoprotein complexes during early events after virus entry. PMID:11070000

  16. Immunogenicity and efficacy of immunodeficiency virus-like particles pseudotyped with the G protein of vesicular stomatitis virus

    SciTech Connect

    Kuate, Seraphin; Stahl-Hennig, Christiane; Stoiber, Heribert; Nchinda, Godwin; Floto, Anja; Franz, Monika; Sauermann, Ulrike; Bredl, Simon; Deml, Ludwig; Ignatius, Ralf; Norley, Steve; Racz, Paul; Tenner-Racz, Klara; Steinman, Ralph M.; Wagner, Ralf; Uberla, Klaus . E-mail: klaus.ueberla@ruhr-uni-bochum.de

    2006-07-20

    Vaccination with exogenous antigens such as recombinant viral proteins, immunodeficiency virus-derived whole inactivated virus particles, or virus-like particles (VLP) has generally failed to provide sufficient protection in animal models for AIDS. Pseudotyping VLPs with the vesicular stomatitis virus G protein (VSV-G), which is known to mediate entry into dendritic cells, might allow more efficient stimulation of immune responses. Therefore, we pseudotyped noninfectious immunodeficiency virus-like particles with VSV-G and carried out a preliminary screen of their immunogenicity and vaccination efficacy. Incorporation of VSV-G into HIV-1 VLPs led to hundred-fold higher antibody titers to HIV-1 Gag and enhancement of T cell responses in mice. Repeated vaccination of rhesus monkeys for 65 weeks with VSV-G pseudotyped simian immunodeficiency virus (SIV)-like particles (VLP[G]) provided initial evidence for efficient suppression of viral load after mucosal challenge with the SIVmac239 virus. Challenge of monkeys after a 28 week vaccination regimen with VLP[G] led to a reduction in peak viremia, but persistent suppression of viral load was not achieved. Due to limitations in the number of animals available for this study, improved efficacy of VSV-G pseudotyped VLPs in nonhuman primates could not be demonstrated. However, mouse experiments revealed that pseudotyping of VLPs with fusion-competent VSV-G clearly improves their immunogenicity. Additional strategies, particularly adjuvants, should be considered to provide greater protection against a challenge with pathogenic immunodeficiency virus.

  17. Differential Cell Tropism of Feline Immunodeficiency Virus Molecular Clones In Vivo

    PubMed Central

    Dean, Gregg A.; Himathongkham, Sunee; Sparger, Ellen E.

    1999-01-01

    Independent studies have demonstrated different cell tropisms for molecular clones of feline immunodeficiency virus (FIV). In this report, we examined three clones, FIV-pF34, FIV-14, and FIV-pPPR, for replication in Crandell feline kidney (CrFK) cells, feline peripheral blood mononuclear cells (PBMC), and feline macrophage cultures. Importantly, cell tropism for these three clones was also examined in vivo. FIV-pF34 replication was efficient in CrFK cells but severely restricted in PBMC, whereas replication of FIV-pPPR was vigorous in PBMC but severely restricted in CrFK cells. FIV-14 replication was productive in both CrFK cells and PBMC. Interestingly, all three molecular clones replicated with similar efficiencies in primary feline monocyte-derived macrophages. In vivo, FIV-pF34 proved least efficient for establishing persistent infection, and proviral DNA when detectable, was localized predominately to nonlymphoid cell populations (macrophages). FIV-pPPR proved most efficient for induction of a persistent viremia in vivo, and proviral DNA was localized predominately in CD4+ and CD8+ lymphocyte subsets. FIV-14 inoculation of cats resulted in an infection characterized by seroconversion and localization of proviral DNA in CD4+ lymphocytes only. Results of this study on diverse FIV molecular clones revealed that in vitro replication efficiency of an FIV isolate in PBMC directly correlated with replication efficiency in vivo, whereas proficiency for replication in macrophages in vitro was not predictive for replication potential in vivo. Also, infection of both CD4+ and CD8+ lymphocyte subsets was associated with higher virus load in vivo. Results of the studies on these three FIV clones, which exhibited differential cell tropism, indicated a correlation between in vitro and in vivo cell tropism and virus replication. PMID:10074104

  18. Correlation of virus load in plasma and lymph node tissue in human immunodeficiency virus infection. INCAS Study Group. Italy, Netherlands, Canada, Australia, and (United) States.

    PubMed

    Harris, M; Patenaude, P; Cooperberg, P; Filipenko, D; Thorne, A; Raboud, J; Rae, S; Dailey, P; Chernoff, D; Todd, J; Conway, B; Montaner, J S

    1997-11-01

    The impact of long-term changes in plasma viremia, produced by effective combination antiretroviral therapy, on human immunodeficiency virus (HIV) burden within tissue reservoirs is unknown. Fifteen patients who had received at least 1 year of therapy with two or three drug combinations of zidovudine, didanosine, and nevirapine had suitable samples of lymph node tissue obtained by ultrasound-guided core needle biopsy. HIV RNA was extracted from homogenized tissue samples and quantitated using a modified branched DNA assay. Results were correlated with antiretroviral treatment effect on the basis of plasma virus load measurements over the preceding 12-18 months. A statistically significant negative correlation was observed between magnitude of treatment effect on plasma viremia and lymph node virus load. These data suggest that combinations of antiretroviral drugs that produce sustained suppression of plasma HIV RNA may also be able to reduce the virus burden in lymphoid tissues.

  19. Human immunodeficiency virus type 1 envelope-specific cytotoxic T lymphocytes response dynamics after prime-boost vaccine regimens with human immunodeficiency virus type 1 canarypox and pseudovirions.

    PubMed

    Arp, J; Rovinski, B; Sambhara, S; Tartaglia, J; Dekaban, G

    1999-01-01

    Virus-specific cytotoxic T lymphocytes (CTLs) may represent significant immune mechanisms in the control of human immunodeficiency virus (HIV) infection and, therefore, CTL induction may be a fundamental goal in the development of an efficacious acquired immunodeficiency syndrome (AIDS) vaccine. In the current study, prime-boost protocols were used to investigate the potential of noninfectious human immunodeficiency virus type 1 (HIV-1) pseudovirions (HIV PSV) in enhancing HIV-specific CTL responses in Balb/c mice primed with the recombinant canarypox vector, vCP205, encoding HIV-1 gp120 (MN strain) in addition to Gag/Protease (HIB strain). The prime-boost immunization regimens were administered intramuscularly and involved injections of vCP205 followed by boosts with HIV PSV. Previous vaccination strategies solely involving vCP205 had induced good cellular immune responses in uninfected human volunteers, despite some limitations. The use of genetically engineered HIV PSV was a logical step in the evaluation of whole noninfectious virus or inactivated virus vaccine strategies, particularly as a potential boosting agent for vCP205-primed recipients. Based on this current study, HIV PSV appeared to have the capability to effectively induce and boost cell-mediated HIV-1-specific responses. In order to observe the immune effects of HIV PSV in a prime-boost immunization strategy, both HIV vaccine immunogens required careful titration in vivo. This suggests that careful consideration should be given to the optimization of immunization protocols destined for human use.

  20. REVIEW OF CONTROL OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION IN NIGERIA.

    PubMed

    Dami, N; Shehu, N Y; Dami, S; Iroezindu, M O

    2015-01-01

    The global scourge of human immunodeficiency virus (HIV) infection is inundating, especially in sub-Saharan Africa and in particular Nigeria which is home to 10% of the world's HIV-infected persons. The target of the millennium development goal 6 is to halt and reverse the spread of HIV/AIDS by 2015. HIV control in Nigeria was initially shrouded in denial and apathy. Subsequently, a more pragmatic approach was launched during the tenure of President Olusegun Obasanjo. Several policies were formulated. The national prevalence of HIV witnessed some progressive decline and is currently 4.1%. There is now improvement in both HIV awareness and counselling and testing. Greater access to antiretroviral therapy and other support services have also been witnessed with over 300,000 persons currently on drugs. Notable achievements have been recorded in prevention of mother to child transmission (PMTC). However, with increased access to antiretroviral therapy, antiretroviral drug resistance has become inevitable. Acquired drug resistance is high-82% and transmitted drug resistance ranges between 0.7 and 4.5%. The achievements were largely facilitated by international partnerships which have become more streamlined in recent years. A sustained shift to indigenously sourced financial and manpower resource has become imperative. It is also important to integrate HIV facilities with other existing health care facilities for sustainability and cost-effectiveness. In an attempt to strengthen the national response, President Goodluck Ebele Jonathan launched the President's Comprehensive Response Plan for HIV/AIDS in Nigeria. It is hoped that this well-articulated policy would be well implemented to significantly reverse the epidemic. PMID:27487603

  1. Declined Neural Efficiency in Cognitively Stable Human Immunodeficiency Virus Patients

    PubMed Central

    Ernst, Thomas; Yakupov, Renat; Nakama, Helenna; Crocket, Grace; Cole, Michael; Watters, Michael; Ricardo-Dukelow, Mary Lynn; Chang, Linda

    2009-01-01

    Objective To determine whether brain activation changes in clinically and neurocognitively normal human immunodeficiency virus (HIV)–infected and in HIV-seronegative control (SN) participants over a 1-year period. Methods Functional magnetic resonance imaging (fMRI) was performed in 32 SN and 31 HIV patients (all with stable combination antiretroviral treatment) at baseline and after 1 year. Each participant performed a set of visual attention tasks with increasing attentional load (from tracking two, three, or four balls). All HIV and SN participants had normal neuropsychological function at both examinations. Results Over 1 year, HIV patients showed no change in their neurocognitive status or in task performance during fMRI. However, HIV patients showed significant 1-year increases in fMRI signals in the prefrontal and posterior parietal cortices for the more difficult tasks, whereas SN control participants showed only decreases in brain activation in these regions. This resulted in significant interactions between HIV status and time of study in left insula, left parietal, left temporal, and several frontal regions (left and right middle frontal gyrus, and anterior cingulate). Interpretation Because fMRI task performance remained unchanged in both groups, the HIV patients appeared to maintain performance by increasing usage of the attention network, whereas the control participants reduced usage of the attention network after 1 year. These findings suggest improved efficiency or a practice effect in the SN participants but declined efficiency of the neural substrate in HIV patients, possibly because of ongoing brain injury associated with the HIV infection, despite their apparent stable clinical course. PMID:19334060

  2. Measuring domestic violence in human immunodeficiency virus-positive women

    PubMed Central

    Patrikar, Seema; Verma, AK; Bhatti, VK; Shatabdi, S

    2012-01-01

    Background Violence affects the lives of millions of women worldwide, in all socioeconomic classes. Violence and the fear of violence are emerging as important risk factor contributing to the vulnerability to human immunodeficiency virus (HIV) infection for women. The objective of the present cross sectional study is to compare the experiences of domestic violence between HIV-positive and HIV-negative married women seeking treatment in a tertiary care hospital. Methods The study is conducted in a tertiary care hospital in Pune on a randomly selected 150 married women (75 HIV-positive and 75 HIV-negative). Informed consent was obtained from all the women and also a trained counsellor was present during the process of data collection. The data was collected by interview method by taking precautions as laid down in the World Health Organization's ethical and safety recommendations for research on domestic violence and using modified conflict tactics scale (CTS). The definition of violence followed is as per the Declaration on the Elimination of Violence against Women, adopted by the United Nations General Assembly in 1993. Results The percentage of women reporting domestic violence is 44.7% (95% confidence interval [CI] = 36.84–52.68). The proportion of physical, emotional and sexual violence reported is 38% (95% CI = 30.49–45.96), 24% (95% CI = 17.67–31.31), and 14.7% (95% CI = 9.66–21.02), respectively. The odds of reporting violence of all forms is significantly higher among HIV-positive women than among HIV-negative women (P<0.05). Univariate and multivariate logistic regression is carried out to examine the possible predictors of domestic violence. Conclusion The findings suggest high proportion of HIV-positive women report violence then HIV-negative women which must be addressed through multilevel prevention approaches. PMID:24669053

  3. REVIEW OF CONTROL OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION IN NIGERIA.

    PubMed

    Dami, N; Shehu, N Y; Dami, S; Iroezindu, M O

    2015-01-01

    The global scourge of human immunodeficiency virus (HIV) infection is inundating, especially in sub-Saharan Africa and in particular Nigeria which is home to 10% of the world's HIV-infected persons. The target of the millennium development goal 6 is to halt and reverse the spread of HIV/AIDS by 2015. HIV control in Nigeria was initially shrouded in denial and apathy. Subsequently, a more pragmatic approach was launched during the tenure of President Olusegun Obasanjo. Several policies were formulated. The national prevalence of HIV witnessed some progressive decline and is currently 4.1%. There is now improvement in both HIV awareness and counselling and testing. Greater access to antiretroviral therapy and other support services have also been witnessed with over 300,000 persons currently on drugs. Notable achievements have been recorded in prevention of mother to child transmission (PMTC). However, with increased access to antiretroviral therapy, antiretroviral drug resistance has become inevitable. Acquired drug resistance is high-82% and transmitted drug resistance ranges between 0.7 and 4.5%. The achievements were largely facilitated by international partnerships which have become more streamlined in recent years. A sustained shift to indigenously sourced financial and manpower resource has become imperative. It is also important to integrate HIV facilities with other existing health care facilities for sustainability and cost-effectiveness. In an attempt to strengthen the national response, President Goodluck Ebele Jonathan launched the President's Comprehensive Response Plan for HIV/AIDS in Nigeria. It is hoped that this well-articulated policy would be well implemented to significantly reverse the epidemic.

  4. Exercise and Human Immunodeficiency Virus (HIV-1) Infection

    NASA Technical Reports Server (NTRS)

    Lawless, DeSales; Jackson, Catherine G. R.; Greenleaf, John E.

    1995-01-01

    The human immune system is highly efficient and remarkably protective when functioning properly. Similar to other physiological systems, it functions best when the body is maintained with a balanced diet, sufficient rest and a moderately stress-free lifestyle. It can be disrupted by inappropriate drug use and extreme emotion or exertion. The functioning of normal or compromised immune systems can be enhanced by properly prescribed moderate exercise conditioning regimens in healthy people, and in some human immunodeficiency virus (HIV-1)-infected patients but not in others who unable to complete an interval training program. Regular exercise conditioning in healthy people reduces cardiovascular risk factors, increases stamina, facilitates bodyweight control, and reduces stress by engendering positive feelings of well-being. Certain types of cancer may also be suppressed by appropriate exercise conditioning. Various exercise regimens are being evaluated as adjunct treatments for medicated patients with the HIV-1 syndrome. Limited anecdotal evidence from patients suggests that moderate exercise conditioning is per se responsible for their survival well beyond expectancy. HIV-1-infected patients respond positively, both physiologically and psychologically, to moderate exercise conditioning. However, the effectiveness of any exercise treatment programme depends on its mode, frequency, intensity and duration when prescribed o complement the pathological condition of the patient. The effectiveness of exercise conditioning regimens in patients with HIV-1 infection is reviewed in this article. In addition, we discuss mechanisms and pathways, involving the interplay of psychological and physiological factors, through which the suppressed immune system can be enhanced. The immune modulators discussed are endogenous opioids, cytokines, neurotransmitters and other hormones. Exercise conditioning treatment appears to be more effective when combined with other stress management

  5. Leishmania and human immunodeficiency virus coinfection: the first 10 years.

    PubMed Central

    Alvar, J; Cañavate, C; Gutiérrez-Solar, B; Jiménez, M; Laguna, F; López-Vélez, R; Molina, R; Moreno, J

    1997-01-01

    Over 850 Leishmania-human immunodeficiency virus (HIV) coinfection cases have been recorded, the majority in Europe, where 7 to 17% of HIV-positive individuals with fever have amastigotes, suggesting that Leishmania-infected individuals without symptoms will express symptoms of leishmaniasis if they become immunosuppressed. However, there are indirect reasons and statistical data demonstrating that intravenous drug addiction plays a specific role in Leishmania infantum transmission: an anthroponotic cycle complementary to the zoonotic one has been suggested. Due to anergy in patients with coinfection, L. infantum dermotropic zymodemes are isolated from patient viscera and a higher L. infantum phenotypic variability is seen. Moreover, insect trypanosomatids that are currently considered nonpathogenic have been isolated from coinfected patients. HIV infection and Leishmania infection each induce important analogous immunological changes whose effects are multiplied if they occur concomitantly, such as a Th1-to-Th2 response switch; however, the consequences of the viral infection predominate. In fact, a large proportion of coinfected patients have no detectable anti-Leishmania antibodies. The microorganisms share target cells, and it has been demonstrated in vitro how L. infantum induces the expression of latent HIV-1. Bone marrow culture is the most useful diagnostic technique, but it is invasive. Blood smears and culture are good alternatives. PCR, xenodiagnosis, and circulating-antigen detection are available only in specialized laboratories. The relationship with low levels of CD4+ cells conditions the clinical presentation and evolution of disease. Most patients have visceral leishmaniasis, but asymptomatic, cutaneous, mucocutaneous, diffuse cutaneous, and post-kala-azar dermal leishmaniasis can be produced by L. infantum. The digestive and respiratory tracts are frequently parasitized. The course of coinfection is marked by a high relapse rate. There is a lack

  6. Phylogenetic Analysis of Human Immunodeficiency Virus Type 2 Group B

    PubMed Central

    Cella, Eleonora; Lo Presti, Alessandra; Giovanetti, Marta; Veo, Carla; Lai, Alessia; Dicuonzo, Giordano; Angeletti, Silvia; Ciotti, Marco; Zehender, Gianguglielmo; Ciccozzi, Massimo

    2016-01-01

    Context: Human immunodeficiency virus type 2 (HIV-2) infections are mainly restricted to West Africa; however, in the recent years, the prevalence of HIV-2 is a growing concern in some European countries and the Southwestern region of India. Despite the presence of different HIV-2 groups, only A and B Groups have established human-to-human transmission chains. Aims: This work aimed to evaluate the phylogeographic inference of HIV-2 Group B worldwide to estimate their data of origin and the population dynamics. Materials and Methods: The evolutionary rates, the demographic history for HIV-2 Group B dataset, and the phylogeographic analysis were estimated using a Bayesian approach. The viral gene flow analysis was used to count viral gene out/in flow among different locations. Results: The root of the Bayesian maximum clade credibility tree of HIV-2 Group B dated back to 1957. The demographic history of HIV-2 Group B showed that the epidemic remained constant up to 1970 when started an exponential growth. From 1985 to early 2000s, the epidemic reached a plateau, and then it was characterized by two bottlenecks and a new plateau at the end of 2000s. Phylogeographic reconstruction showed that the most probable location for the root of the tree was Ghana. Regarding the viral gene flow of HIV-2 Group B, the only observed viral gene flow was from Africa to France, Belgium, and Luxembourg. Conclusions: The study gives insights into the origin, history, and phylogeography of HIV-2 Group B epidemic. The growing number of infections of HIV-2 worldwide indicates the need for strengthening surveillance. PMID:27621561

  7. Phylogenetic Analysis of Human Immunodeficiency Virus Type 2 Group B

    PubMed Central

    Cella, Eleonora; Lo Presti, Alessandra; Giovanetti, Marta; Veo, Carla; Lai, Alessia; Dicuonzo, Giordano; Angeletti, Silvia; Ciotti, Marco; Zehender, Gianguglielmo; Ciccozzi, Massimo

    2016-01-01

    Context: Human immunodeficiency virus type 2 (HIV-2) infections are mainly restricted to West Africa; however, in the recent years, the prevalence of HIV-2 is a growing concern in some European countries and the Southwestern region of India. Despite the presence of different HIV-2 groups, only A and B Groups have established human-to-human transmission chains. Aims: This work aimed to evaluate the phylogeographic inference of HIV-2 Group B worldwide to estimate their data of origin and the population dynamics. Materials and Methods: The evolutionary rates, the demographic history for HIV-2 Group B dataset, and the phylogeographic analysis were estimated using a Bayesian approach. The viral gene flow analysis was used to count viral gene out/in flow among different locations. Results: The root of the Bayesian maximum clade credibility tree of HIV-2 Group B dated back to 1957. The demographic history of HIV-2 Group B showed that the epidemic remained constant up to 1970 when started an exponential growth. From 1985 to early 2000s, the epidemic reached a plateau, and then it was characterized by two bottlenecks and a new plateau at the end of 2000s. Phylogeographic reconstruction showed that the most probable location for the root of the tree was Ghana. Regarding the viral gene flow of HIV-2 Group B, the only observed viral gene flow was from Africa to France, Belgium, and Luxembourg. Conclusions: The study gives insights into the origin, history, and phylogeography of HIV-2 Group B epidemic. The growing number of infections of HIV-2 worldwide indicates the need for strengthening surveillance.

  8. Hepatitis B Virus Infection in Human Immunodeficiency Virus Infected Southern African Adults: Occult or Overt – That Is the Question

    PubMed Central

    Bell, Trevor G.; Makondo, Euphodia; Martinson, Neil A.; Kramvis, Anna

    2012-01-01

    Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share transmission routes and are endemic in sub-Saharan Africa. The objective of the present study was to use the Taormina definition of occult HBV infection, together with stringent amplification conditions, to determine the prevalence and characteristics of HBV infection in antiretroviral treatment (ART)-naïve HIV+ve adults in a rural cohort in South Africa. The presence of HBV serological markers was determined by enzyme linked immunoassay (ELISA) tests. HBV DNA-positivity was determined by polymerase chain reaction (PCR) of at least two of three different regions of the HBV genome. HBV viral loads were determined by real-time PCR. Liver fibrosis was determined using the aspartate aminotransferase-to-platelet ratio index. Of the 298 participants, 231 (77.5%) showed at least one HBV marker, with 53.7% HBV DNA−ve (resolved) and 23.8% HBV DNA+ve (current) [8.7% HBsAg+ve: 15.1% HBsAg−ve]. Only the total number of sexual partners distinguished HBV DNA+ve and HBV DNA−ve participants, implicating sexual transmission of HBV and/or HIV. It is plausible that sexual transmission of HBV and/or HIV may result in a new HBV infection, superinfection and re-activation as a consequence of immunesuppression. Three HBsAg−ve HBV DNA+ve participants had HBV viral loads <200 IU/ml and were therefore true occult HBV infections. The majority of HBsAg−ve HBV DNA+ve participants did not differ from HBsAg+ve HBV DNA+ve (overt) participants in terms of HBV viral loads, ALT levels or frequency of liver fibrosis. Close to a quarter of HIV+ve participants were HBV DNA+ve, of which the majority were HBsAg−ve and were only detected using nucleic acid testing. Detection of HBsAg−ve HBV DNA+ve subjects is advisable considering they were clinically indistinguishable from HBsAg+ve HBV DNA+ve individuals and should not be overlooked, especially if lamivudine is included in the ART. PMID:23049685

  9. A monoclonal antibody to human immunodeficiency virus type 1 which mediates cellular cytotoxicity and neutralization.

    PubMed Central

    Broliden, P A; Ljunggren, K; Hinkula, J; Norrby, E; Akerblom, L; Wahren, B

    1990-01-01

    Monoclonal antibodies (MAbs) were raised against human immunodeficiency virus type 1 gp120. One MAb, P4/D10, was found to mediate highly efficient antibody-dependent cellular cytotoxicity and virus neutralization. The reactivity was located to a major neutralizing region (amino acids 304 to 323) on gp120. Five other MAbs with a similar epitopic reactivity did not show any antibody-dependent cellulan cytotoxicity activity but had a virus-neutralizing capacity. PMID:2296090

  10. Susceptibility of human immunodeficiency virus to antiviral agents measured by infectious virus yield reduction.

    PubMed

    Dianzani, F; Capobianchi, M R; Antonelli, G; Amicucci, P; De Marco, F

    1989-01-01

    Under single growth cycle conditions in C8166 lymphoblastoid cells human immunodeficiency virus shows a replication curve which is completed at 24 h post-infection. At lower multiplicity of infection virus yield peaks at approximately 72 h post-infection but in both cases the titer of the virus released in the medium is negligible with respect to that which remains cell-associated. A method based on back-titration of virus in cryolysates of C8166 cells infected with HIV and treated with antiviral compounds has been used to evaluate HIV sensitivity to such agents. Under single growth cycle conditions dose response curves appear linear and permit rapid and accurate determination of the endpoint activity. Under multiple growth cycle conditions the inhibitory activity may be measured during the exponential growth phase, at 48 h post-infection. This method, which directly measures production of infectious virus rather than indirect probes of viral replication such as reverse transcriptase or antigen production, offers the advantage of a precise determination of the degree of activity of antivirals also acting on viral assembly or release.

  11. Dual infection with dengue virus 3 and human immunodeficiency virus 1 in Havana, Cuba.

    PubMed

    Gonzalez, Daniel; Limonta, Daniel; Bandera, Juan Francisco; Perez, Jorge; Kouri, Gustavo; Guzman, Maria G

    2009-01-01

    Although dengue virus (DEN) endemic regions overlap with human immunodeficiency virus 1 (HIV) high incidence areas, little has been documented on HIV and DEN mixed infection. Here we report DEN/HIV concurrent infections recorded during the DEN-3 epidemic in 2001-2002 in Havana. Serologic-confirmed DEN is described in two HIV-infected subjects with dengue fever symptoms. Although patients had dengue disease, the CD4+ cells remained within normal levels and no accelerated progression of HIV disease was observed. To our knowledge, DEN cases caused by DEN-3 in HIV-infected individuals have not been reported previously. Further research is needed to diagnose this likely underreported mixed viral infection in DEN endemic areas.

  12. Improbability of Effective Vaccination Against Human Immunodeficiency Virus Because of Its Intracellular Transmission and Rectal Portal of Entry

    NASA Astrophysics Data System (ADS)

    Sabin, Albert B.

    1992-09-01

    The worldwide effort to produce a vaccine against AIDS continues to disregard the fact that even human immunodeficiency virus (HIV)-specific neutralizing antibodies and cell-mediated immunity are ineffective against virus within cells without viral antigens on the cell membrane-and that much of HIV infection is transmitted in this manner. According to a recent report, a simian immunodeficiency virus vaccine that protected monkeys against an intravenous challenge with cell-free virus was, as predicted, ineffective against an intravenous challenge with the same amount of virus in infected cells. Moreover, antibody and HIV have been found to coexist in cell-free plasma from asymptomatic and symptomatic patients. Excluding direct introduction of HIV into the bloodstream, the most common and efficient form of transmission of HIV infection is by receptive anal intercourse, and semen contains large numbers of infected cells per milliliter. Recent reports showing that colorectal cells can be persistently infected by HIV and that HIV RNA and cDNA are present in the cells of the colon of dead AIDS patients indicate that either cell-free or intracellular HIV has the capacity to multiply at the portal of entry in the colorectal area without interference from neutralizing antibodies. The available data provide no basis for testing any HIV vaccine in human beings either before or after infection. The main challenge is to find a way to kill cells with chromosomally integrated HIV cDNA without harming normal cells, perhaps by identifying repressor proteins that might be produced by the cells with integrated HIV cDNA and thus could become specific targets for cell-killing drugs.

  13. Slow CD4+ T-Cell Recovery in Human Immunodeficiency Virus/Hepatitis B Virus-Coinfected Patients Initiating Truvada-Based Combination Antiretroviral Therapy in Botswana

    PubMed Central

    Anderson, Motswedi; Gaseitsiwe, Simani; Moyo, Sikhulile; Thami, Kerapetse P.; Mohammed, Terence; Setlhare, Ditiro; Sebunya, Theresa K.; Powell, Eleanor A.; Makhema, Joseph; Blackard, Jason T.; Marlink, Richard; Essex, Max; Musonda, Rosemary M.

    2016-01-01

    Background. Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection has emerged as an important cause of morbidity and mortality. We determined the response to Truvada-based first-line combination antiretroviral therapy (cART) in HIV/HBV-coinfected verus HIV-monoinfected patients in Botswana. Methods. Hepatitis B virus surface antigen (HBsAg), HBV e antigen (HBeAg), and HBV deoxyribonucleic acid (DNA) load were determined from baseline and follow-up visits in a longitudinal cART cohort of Truvada-based regimen. We assessed predictors of HBV serostatus and viral suppression (undetectable HBV DNA) using logistic regression techniques. Results. Of 300 participants, 28 were HBsAg positive, giving an HIV/HBV prevalence of 9.3% (95% confidence interval [CI], 6.3–13.2), and 5 of these, 17.9% (95% CI, 6.1–36.9), were HBeAg positive. There was a reduced CD4+ T-cell gain in HIV/HBV-coinfected compared with HIV-monoinfected patients. Hepatitis B virus surface antigen and HBeAg loss was 38% and 60%, respectively, at 24 months post-cART initiation. The HBV DNA suppression rates increased with time on cART from 54% to 75% in 6 and 24 months, respectively. Conclusions. Human immunodeficiency virus/HBV coinfection negatively affected immunologic recovery compared with HIV-1C monoinfection. Hepatitis B virus screening before cART initiation could help improve HBV/HIV treatment outcomes and help determine treatment options when there is a need to switch regimens. PMID:27800524

  14. Personal and psychosocial characteristics associated with psychiatric conditions among women with human immunodeficiency virus.

    PubMed

    Sherbourne, Cathy; Griffith Forge, Nell; Kung, Fuan-Yue; Orlando, Maria; Tucker, Joan

    2003-01-01

    This study presents information on correlates of mental health and substance abuse problems among women with human immunodeficiency virus (HIV), a particularly vulnerable, poor and minority population. Data are from 847 women in the HIV Cost and Services Utilization Study, a national probability sample of adults with known human immunodeficiency virus infection. Fifty-five percent of women manifested a probable psychiatric condition. Results indicated that increased risk for psychiatric conditions among these women was associated with younger age, having acquired immunodeficiency virus (rather than asymptomatic), using avoidant coping strategies, reporting increased conflict with others, and prior physical abuse, needing income assistance, and putting off going to the doctor because of caring for someone else. Findings suggest we need to address women's need for safety from assaultive partners and that we may need special programs for women burdened with having to care for others.

  15. Decline in CD4+ cell numbers in cats with naturally acquired feline immunodeficiency virus infection.

    PubMed

    Hoffmann-Fezer, G; Thum, J; Ackley, C; Herbold, M; Mysliwietz, J; Thefeld, S; Hartmann, K; Kraft, W

    1992-03-01

    T-cell subsets were studied by fluorescence-activated cell sorter analysis in 57 feline immunodeficiency virus (FIV)-seropositive cats with naturally acquired FIV infection to see whether CD4(+)-CD8+ alterations were comparable to those observed in human immunodeficiency virus-infected patients. CD4+ values were decreased and CD8+ values were increased. The CD4+/CD8+ ratio was reduced to 1.6, compared with 3.3 in 33 FIV-seronegative control cats. Variance analysis of data showed a significant influence of FIV seropositivity, sex, and spaying of female cats on CD4+ values. CD8+ values were significantly influenced by FIV seropositivity, age, and breed. These findings indicate a similarity between FIV and human immunodeficiency virus infections, as far as alterations of T-cell subsets are concerned. PMID:1310760

  16. Recent key advances in human immunodeficiency virus medicine and implications for China

    PubMed Central

    2010-01-01

    In this article we summarize several recent major developments in human immunodeficiency virus treatment, prevention, outcome, and social policy change. Updated international guidelines endorse more aggressive treatment strategies and safer antiretroviral drugs. New antiretroviral options are being tested. Important lessons were learned in the areas of human immunodeficiency virus vaccines and microbicide gels from clinical studies, and additional trials in prevention, especially pre-exposure prophylaxis, are nearing completion. Insight into the role of the virus in the pathogenesis of diseases traditionally thought to be unrelated to acquired immunodeficiency syndrome has become a driving force for earlier and universal therapy. Lastly, we review important achievements of and future challenges facing China as she steps into her eighth year of the National Free Antiretroviral Treatment Program. PMID:20500898

  17. Successful Orthotopic Heart Transplantation and Immunosuppressive Management in 2 Human Immunodeficiency Virus-Seropositive Patients.

    PubMed

    Conte, Antonio Hernandez; Kittleson, Michelle M; Dilibero, Deanna; Hardy, W David; Kobashigawa, Jon A; Esmailian, Fardad

    2016-02-01

    Few orthotopic heart transplantations have been performed in patients infected with the human immunodeficiency virus since the first such case was reported in 2001. Since that time, advances in highly active antiretroviral therapy have resulted in potent and durable suppression of the causative human immunodeficiency virus-accompanied by robust immune reconstitution, reversal of previous immunodeficiency, a marked decrease in opportunistic and other infections, and near-normal long-term survival. Although human immunodeficiency virus infection is not an absolute contraindication, few centers in the United States and Canada have performed heart transplantations in this patient population; these patients have been de facto excluded from this procedure in North America. Re-evaluation of the reasons for excluding these patients from cardiac transplantation is warranted in light of such significant advances in antiretroviral therapy. This case report documents successful orthotopic heart transplantation in 2 patients infected with human immunodeficiency virus, and we describe their antiretroviral therapy and immunosuppressive management challenges. Both patients were doing well without sequelae 43 and 38 months after transplantation.

  18. The human immunodeficiency virus-reverse transcriptase inhibition activity of novel pyridine/pyridinium-type fullerene derivatives.

    PubMed

    Yasuno, Takumi; Ohe, Tomoyuki; Takahashi, Kyoko; Nakamura, Shigeo; Mashino, Tadahiko

    2015-08-15

    In the present study, we describe the synthesis of a novel set of pyridine/pyridinium-type fullerene derivatives. The products were assessed for human immunodeficiency virus-reverse transcriptase inhibition activities. All novel fullerene derivatives showed potent human immunodeficiency virus-reverse transcriptase inhibition without cytotoxicity.

  19. 38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... partner and that the disclosure is necessary to protect the health of the spouse or sexual partner. (c) A... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject...

  20. 38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... partner and that the disclosure is necessary to protect the health of the spouse or sexual partner. (c) A... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject...

  1. 38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... partner and that the disclosure is necessary to protect the health of the spouse or sexual partner. (c) A... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject...

  2. 38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1... immunodeficiency virus to public health authorities. (a) In the case of any record which is maintained in connection with the performance of any program or activity relating to infection with the HIV,...

  3. 38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1... immunodeficiency virus to public health authorities. (a) In the case of any record which is maintained in connection with the performance of any program or activity relating to infection with the HIV,...

  4. 38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject to... indicating that a patient is infected with the HIV if the disclosure is made to the spouse of the patient,...

  5. 38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject to... indicating that a patient is infected with the HIV if the disclosure is made to the spouse of the patient,...

  6. Reversion of a human immunodeficiency virus type 1 integrase mutant at a second site restores enzyme function and virus infectivity.

    PubMed Central

    Taddeo, B; Carlini, F; Verani, P; Engelman, A

    1996-01-01

    The integration of a DNA copy of the retroviral RNA genome into the host cell genome is essential for viral replication. The virion-associated integrase protein, encoded by the 3' end of the viral pol gene, is required for integration. Stable virus-producing T-cell lines were established for replication-defective human immunodeficiency virus type 1 carrying single amino acid substitutions at conserved residues in the catalytic domain of integrase. Phenotypically reverted virus was detected 12 weeks after transfection with the integrase mutant carrying the P-109-->S mutation (P109S). Unlike the defective P109S virus, the revertant virus (designated P109SR) grew in CD4+ SupT1 cells. In addition to the Ser substitution at Pro-109, P109SR had a second substitution of Ala for Thr at position 125 in integrase. Site-directed mutagenesis was used to show that the P109S T125A genotype was responsible for the P109SR replication phenotype. The T125A substitution also rescued the in vitro enzyme activities of recombinant P109S integrase protein. P109S integrase did not display detectable 3' processing or DNA strand transfer activity, although 5 to 10% of wild-type disintegration activity was detected. P109S T125A integrase displayed nearly wild-type levels of 3' processing, DNA strand transfer, and disintegration activities, confirming that T125A is a second-site intragenic suppressor of P109S. P109S integrase ran as a large aggregate on a size exclusion column, whereas wild-type integrase ran as a monomer and P109S T125A integrase ran as a mixed population. Pro-109 and Thr-125 are not immediately adjacent in the crystal structure of the integrase catalytic domain. We suggest that the T125A substitution restores integrase function by stabilizing a structural alteration(s) induced by the P109S mutation. PMID:8970947

  7. An integrated system to study multiply substituted human immunodeficiency virus type 1 reverse transcriptase.

    PubMed

    Boretto, J; Longhi, S; Navarro, J M; Selmi, B; Sire, J; Canard, B

    2001-05-01

    We describe a gene system allowing the facile production of multiply substituted reverse transcriptases (RTs), the enzymatic characterization of these purified RTs, and the study of these mutations in the defined genetic background of the macrophagetropic, non-laboratory-adapted human immunodeficiency virus type 1 (HIV-1) AD8 strain. Thirteen unique silent restriction sites were introduced in the pol gene encoding HIV-1 RT, allowing easy introduction of mutations. To simplify genetic manipulation and generate p66/p51 heterodimers in Escherichia coli, a gene construct of the viral protease alone was optimized for expression from a separate vector carrying a p15A origin of replication. Active-site titration experiments using pre-steady-state kinetics showed that our system yields a higher proportion of active enzyme than that obtained by alternate methods. To facilitate phenotype/genotype correlations, the modified RT gene was designed to be easily reintroduced into a recombinant proviral AD8 HIV-1 DNA. Infectious viruses made from this vector were undistinguishable from wild-type AD8 HIV-1, an isolate able to infect peripheral blood mononuclear cells and macrophages. Thus, the pol gene can tolerate many silent mutations in the polymerase domain without affecting the functionality of the HIV-1 genome. The system was validated biochemically and virologically using the V75T substitution associated with stavudine resistance.

  8. Transcriptional Activation of the Integrated Chromatin-Associated Human Immunodeficiency Virus Type 1 Promoter

    PubMed Central

    El Kharroubi, Aboubaker; Piras, Graziella; Zensen, Ralf; Martin, Malcolm A.

    1998-01-01

    The regulation of human immunodeficiency virus type 1 (HIV-1) gene expression involves a complex interplay between cellular transcription factors, chromatin-associated proviral DNA, and the virus-encoded transactivator protein, Tat. Here we show that Tat transactivates the integrated HIV-1 long terminal repeat (LTR), even in the absence of detectable basal promoter activity, and this transcriptional activation is accompanied by chromatin remodeling downstream of the transcription initiation site, as monitored by increased accessibility to restriction endonucleases. However, with an integrated promoter lacking both Sp1 and NF-κB sites, Tat was unable to either activate transcription or induce changes in chromatin structure even when it was tethered to the HIV-1 core promoter upstream of the TATA box. Tat responsiveness was observed only when Sp1 or NF-κB was bound to the promoter, implying that Tat functions subsequent to the formation of a specific transcription initiation complex. Unlike Tat, NF-κB failed to stimulate the integrated transcriptionally silent HIV-1 promoter. Histone acetylation renders the inactive HIV-1 LTR responsive to NF-κB, indicating that a suppressive chromatin structure must be remodeled prior to transcriptional activation by NF-κB. Taken together, these results suggest that Sp1 and NF-κB are required for the assembly of transcriptional complexes on the integrated viral promoter exhibiting a continuum of basal activities, all of which are fully responsive to Tat. PMID:9566873

  9. Transcriptional activation of the integrated chromatin-associated human immunodeficiency virus type 1 promoter.

    PubMed

    El Kharroubi, A; Piras, G; Zensen, R; Martin, M A

    1998-05-01

    The regulation of human immunodeficiency virus type 1 (HIV-1) gene expression involves a complex interplay between cellular transcription factors, chromatin-associated proviral DNA, and the virus-encoded transactivator protein, Tat. Here we show that Tat transactivates the integrated HIV-1 long terminal repeat (LTR), even in the absence of detectable basal promoter activity, and this transcriptional activation is accompanied by chromatin remodeling downstream of the transcription initiation site, as monitored by increased accessibility to restriction endonucleases. However, with an integrated promoter lacking both Sp1 and NF-kappaB sites, Tat was unable to either activate transcription or induce changes in chromatin structure even when it was tethered to the HIV-1 core promoter upstream of the TATA box. Tat responsiveness was observed only when Sp1 or NF-kappaB was bound to the promoter, implying that Tat functions subsequent to the formation of a specific transcription initiation complex. Unlike Tat, NF-kappaB failed to stimulate the integrated transcriptionally silent HIV-1 promoter. Histone acetylation renders the inactive HIV-1 LTR responsive to NF-kappaB, indicating that a suppressive chromatin structure must be remodeled prior to transcriptional activation by NF-kappaB. Taken together, these results suggest that Sp1 and NF-kappaB are required for the assembly of transcriptional complexes on the integrated viral promoter exhibiting a continuum of basal activities, all of which are fully responsive to Tat. PMID:9566873

  10. In vitro infection of natural killer cells with different human immunodeficiency virus type 1 isolates.

    PubMed Central

    Chehimi, J; Bandyopadhyay, S; Prakash, K; Perussia, B; Hassan, N F; Kawashima, H; Campbell, D; Kornbluth, J; Starr, S E

    1991-01-01

    Natural killer (NK) cells are a discrete subset of leukocytes, distinct from T and B lymphocytes. NK cells mediate spontaneous non-MHC-restricted killing of a wide variety of target cells without prior sensitization and appear to be involved in initial protection against certain viral infections. Depressed NK cell-mediated cytotoxicity, one of the many immunological defects observed in AIDS patients, may contribute to secondary virus infections. Here we report that clonal and purified polyclonal populations of NK cells, which expressed neither surface CD4 nor CD4 mRNA, were susceptible to infection with various isolates of human immunodeficiency virus type 1 (HIV-1). Viral replication was demonstrated by detection of p24 antigen intracellularly and in culture supernatants, by the presence of HIV DNA within infected cells, and by the ability of supernatants derived from HIV-infected NK cells to infect peripheral blood mononuclear cells or CD4+ cell lines. Infection of NK cells was not blocked by anti-CD4 or anti-Fc gamma RIII monoclonal antibodies. NK cells from HIV-infected and uninfected cultures were similar in their ability to lyse three different target cells. Considerable numbers of cells died in HIV-infected NK cell cultures. These results suggest that loss of NK cells in AIDS patients is a direct effect of HIV infection but that reduced NK cell function involves another mechanism. The possibility that NK cells serve as a potential reservoir for HIV-1 must be considered. Images PMID:1672164

  11. Genital ulcers: etiology, clinical diagnosis, and associated human immunodeficiency virus infection in Kingston, Jamaica.

    PubMed

    Behets, F M; Brathwaite, A R; Hylton-Kong, T; Chen, C Y; Hoffman, I; Weiss, J B; Morse, S A; Dallabetta, G; Cohen, M S; Figueroa, J P

    1999-05-01

    Individuals presenting consecutively with genital ulcers in Kingston, Jamaica, underwent serological testing for human immunodeficiency virus (HIV) infection, chlamydial infection, and syphilis. Ulcer material was analyzed by multiplex polymerase chain reaction (M-PCR) analysis. DNA from herpes simplex virus (HSV), Haemophilus ducreyi, and Treponema pallidum was detected in 158 (52.0%), 72 (23.7%), and 31 (10.2%) of 304 ulcer specimens. Of the 304 subjects, 67 (22%) were HIV-seropositive and 64 (21%) were T. pallidum-seroreactive. Granuloma inguinale was clinically diagnosed in nine (13.4%) of 67 ulcers negative by M-PCR analysis and in 12 (5.1%) of 237 ulcers positive by M-PCR analysis (P = .03). Lymphogranuloma venereum was clinically diagnosed in eight patients. Compared with M-PCR analysis, the sensitivity and specificity of a clinical diagnosis of syphilis, herpes, and chancroid were 67.7%, 53.8%, and 75% and 91.2%, 83.6%, and 75.4%, respectively. Reactive syphilis serology was 74% sensitive and 85% specific compared with M-PCR analysis. Reported contact with a prostitute in the preceding 3 months was associated with chancroid (P = .009), reactive syphilis serology (P = .011), and HIV infection (P = .007). The relatively poor accuracy of clinical and locally available laboratory diagnoses pleads for syndromic management of genital ulcers in Jamaica. Prevention efforts should be intensified.

  12. Selection, recombination, and G----A hypermutation of human immunodeficiency virus type 1 genomes.

    PubMed Central

    Vartanian, J P; Meyerhans, A; Asjö, B; Wain-Hobson, S

    1991-01-01

    Human immunodeficiency virus type 1 (HIV-1) isolates are genetically so heterogeneous that they must be described in terms of populations of related but distinct genomes called quasispecies. A recent study of the influence of ex vivo culturing on HIV-1 quasispecies demonstrated that usually low-abundance genomes outgrew the more prominent forms. Here it is shown that multiple passages of an HIV-1 isolate on peripheral blood mononuclear cells resulted in the outgrowth of very minor forms. A single passage of equal proportions of supernatants to either of the established lymphocyte and monocyte cell lines Molt-3 and U937-2, respectively, resulted in the isolation of different sets of minor forms. Recombination between component sequences was observed. Extensive and monotonous base substitutions of G----A (G----A hypermutation) were evident in many sequences. A strong preference for the transition within the GpA dinucleotide was observed. Dislocation mutagenesis, in this case, a -1 slippage or dislocation of the primer with respect to the template, during DNA synthesis by the HIV-1 reverse transcriptase would explain this bias. When the consequences of polymerase errors, recombination, hypermutation, and instability are added to the genetic description of HIV-1, the real complexity of this virus starts to become apparent. PMID:2002543

  13. Structure-based mutagenesis of the catalytic domain of human immunodeficiency virus type 1 integrase.

    PubMed Central

    Engelman, A; Liu, Y; Chen, H; Farzan, M; Dyda, F

    1997-01-01

    Two different crystal structures of the human immunodeficiency virus type 1 (HIV-1) integrase (IN) catalytic domain were analyzed for interactions at the enzyme active site. Gln-62 and Glu-92 interact with active-site residue Asp-64, and Lys-136 interacts with active-site residue Asp-116 across a dimer interface. Conservative and nonconservative substitutions were introduced at these positions to probe the roles of these interactions in HIV-1 integration. Purified mutant proteins were assayed for in vitro 3' processing, DNA strand transfer, and disintegration activities, and HIV-1 mutants were assayed for virion protein composition, reverse transcription, and infectivities in human cell lines. Each of the mutant IN proteins displayed wild-type disintegration activity, indicating that none of the interactions is essential for catalysis. Mutants carrying Gln or Ala for Glu-92 displayed wild-type activities, but substituting Lys for Glu-92 reduced in vitro 3' processing and DNA strand transfer activities 5- to 10-fold and yielded a replication-defective IN active-site mutant viral phenotype. Substituting Glu for Gln-62 reduced in vitro 3' processing and DNA strand transfer activities 5- to 10-fold without grossly affecting viral replication kinetics, suggesting that HIV-1 can replicate in T-cell lines with less than the wild-type level of IN activity. The relationship between IN solubility and HIV-1 replication was also investigated. We previously showed that substituting Lys for Phe-185 dramatically increased the solubility of recombinant IN but caused an HIV-1 particle assembly defect. Mutants carrying His at this position displayed increased solubility and wild-type replication kinetics, showing that increased IN solubility per se is not detrimental to virus growth. PMID:9094622

  14. Practice Bulletin No. 167 Summary: Gynecologic Care for Women and Adolescents With Human Immunodeficiency Virus.

    PubMed

    2016-10-01

    In the United States in 2013, there were an estimated 226,000 women and adolescents living with human immunodeficiency virus (HIV) infection (1). Women with HIV are living longer, healthier lives, so the need for routine and problem-focused gynecologic care has increased. The purpose of this document is to educate clinicians about basic health screening and care, family planning, prepregnancy care, and managing common gynecologic problems for women and adolescents who are infected with HIV. For information on screening guidelines, refer to the American College of Obstetricians and Gynecologists' Committee Opinion No. 596, Routine Human Immunodeficiency Virus Screening (2). PMID:27661642

  15. Practice Bulletin No. 167: Gynecologic Care for Women and Adolescents With Human Immunodeficiency Virus.

    PubMed

    2016-10-01

    In the United States in 2013, there were an estimated 226,000 women and adolescents living with human immunodeficiency virus (HIV) infection (1). Women with HIV are living longer, healthier lives, so the need for routine and problem-focused gynecologic care has increased. The purpose of this document is to educate clinicians about basic health screening and care, family planning, prepregnancy care, and managing common gynecologic problems for women and adolescents who are infected with HIV. For information on screening guidelines, refer to the American College of Obstetricians and Gynecologists' Committee Opinion No. 596, Routine Human Immunodeficiency Virus Screening (2). PMID:27661659

  16. C5A Protects Macaques from Vaginal Simian-Human Immunodeficiency Virus Challenge

    PubMed Central

    Veazey, Ronald S.; Chatterji, Udayan; Bobardt, Michael; Russell-Lodrigue, Kasi E.; Li, Jian; Wang, Xiaolei

    2015-01-01

    A safe and effective vaginal microbicide could decrease human immunodeficiency virus (HIV) transmission in women. Here, we evaluated the safety and microbicidal efficacy of a short amphipathic peptide, C5A, in a rhesus macaque model. We found that a vaginal application of C5A protects 89% of the macaques from a simian-human immunodeficiency virus (SHIV-162P3) challenge. We observed no signs of lesions or inflammation in animals vaginally treated with repeated C5A applications. With its noncellular cytotoxic activity and rare mechanism of action, C5A represents an attractive microbicidal candidate. PMID:26552985

  17. Inhibition of simian immunodeficiency virus by foamy virus vectors expressing siRNAs

    SciTech Connect

    Park, Jeonghae; Nadeau, Peter; Zucali, James R.; Johnson, Calvin M.; Mergia, Ayalew . E-mail: mergiaa@mail.vetmed.ufl.edu

    2005-12-20

    Viral vectors available for gene therapy are either inefficient or suffer from safety concerns for human applications. Foamy viruses are non-pathogenic retroviruses that offer several unique opportunities for gene transfer in various cell types from different species. In this report, we describe the use of simian foamy virus type 1 (SFV-1) vector to examine the efficacy of therapeutic genes. Hairpin short-interfering RNA (siRNA) that targets the simian immunodeficiency virus (SIV) rev/env was placed under the control of the PolIII U6 snRNA promoter for expression and screened for silencing target genes using cognate target-reporter fusions. We have identified an effective siRNA (designated R2) which reduces the rev and env gene expression by 89% and 95%, respectively. Using the simian foamy virus type 1 (SFV-1) based vector, we delivered the PolIII expressed R2 siRNA into cultured cells and challenged with SIV. The results show that the R2 siRNA is a potent inhibitor of SIV replication as determined by p27 expression and reverse transcriptase assays. Vectors based on a non-pathogenic SFV-1 vector may provide a safe and efficient alternative to currently available vectors, and the SIV model will help devise protocols for effective anti-HIV gene therapy.

  18. Pharmacologic management of human immunodeficiency virus wasting syndrome.

    PubMed

    Badowski, Melissa; Pandit, Neha Sheth

    2014-08-01

    Pharmacologic interventions for human immunodeficiency virus (HIV) wasting have been studied since the 1990s, but the results of these interventions have been difficult to compare because the studies used different HIV wasting definitions and assessed various patient outcomes. Thus, we performed a systematic review of the current literature to identify studies that evaluated pharmacologic management of HIV wasting and to compare and contrast treatment options. Further, we provide a comprehensive review of these treatment options and describe the definition of HIV wasting used in each study, the outcomes assessed, and whether antiretroviral therapy was used during the HIV wasting treatment. Literature searches of the PubMed/Medline (1946-2014) and Google Scholar databases were performed, and a review of the bibliographies of retrieved articles was performed to identify additional references. Only English-language articles pertaining to humans and HIV-infected individuals were evaluated. Thirty-six studies were identified that assessed pharmacologic interventions to treat HIV wasting. Appetite stimulants, such as megestrol acetate, have been shown to increase total body weight (TBW) and body mass index in HIV-infected patients with wasting. Studies evaluating dronabinol showed conflicting data on TBW increases, but the drug may have minimal benefit on body composition compared with other appetite stimulants. Testosterone has been shown to be effective in HIV wasting for those who suffer from hypogonadism. Recombinant human growth hormone has been evaluated for HIV wasting and has shown promising results for TBW and lean body mass increases. Thalidomide has been studied; however, its use is limited due to its toxicities. Although megestrol acetate and dronabinol are approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV wasting, it is important to recognize other comorbidities such as depression or hypogonadism that may contribute to the

  19. Variants selected by treatment of human immunodeficiency virus-infected cells with an immunotoxin

    PubMed Central

    1990-01-01

    An immunotoxin has been made by coupling anti-human immunodeficiency virus (HIV) envelope antibody 907 to ricin A chain (907-RAC). 907 recognizes an epitope within the immunodominant PB-1 loop of gp120. Variant cells were selected by cloning persistently infected H9/human T lymphocyte virus IIIB cells in the presence of the immunotoxin. Clones resistant to 907-RAC arose at a frequency of 0.1-1.0%. Seven clones were selected for intensive analysis. When studied, these clones fell into two distinct groups, members of which appeared to be identical, suggesting that the variation arose before the selection process. In contrast to the parent cells, none of the cloned variants produced infectious HIV. The first set of clones, designated the "E" variants, expressed decreased levels of the HIV envelope on the cell surface. However, levels of intracellular HIV antigens and reverse transcriptase were equal to or greater than that of the parental cell line. Radioimmunoprecipitation demonstrated that the gp160 was truncated to 145 kD (gp120 was normal length), capable of binding to CD4, and, unlike normal gp160, was released in its unprocessed form into the cellular supernatant. Sequence analysis demonstrated that a deletion at codon 687 of the envelope gene resulted in the production of this truncated protein. Ultrastructural analysis of E variants demonstrated some budding forms of virus, but also large numbers of HIV within intracellular vesicles. The second set of variants, the "F" series, produced no HIV antigens, reverse transcriptase, nor was there ultrastructural evidence of virus. However, proviral DNA was present. Virus could not be induced with agents known to activate latent HIV. These cells also lacked cell surface CD4 and could not be infected with HIV. These studies demonstrate that variation in HIV can affect the phenotype of the cells carrying the altered virus, allowing for escape from immunologic destruction. The E variants may serve as prototypes for

  20. Shedding of Hepatitis C Virus in Semen of Human Immunodeficiency Virus-Infected Men

    PubMed Central

    Turner, Samuel S.; Gianella, Sara; Yip, Marcus J-S.; van Seggelen, Wouter O.; Gillies, Robert D.; Foster, Andrew L.; Barbati, Zachary R.; Smith, Davey M.; Fierer, Daniel S.

    2016-01-01

    Background. The epidemic of sexually transmitted hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) has been documented for over a decade. Despite this, there is no consensus as to the risk factors for sexual acquisition of HCV in these men. Methods. We obtained paired semen and blood samples at 2-week intervals from HIV-infected MSM with recent and chronic HCV infection and quantified HCV in semen. Results. Hepatitis C virus was quantified in 59 semen specimens from 33 men. Hepatitis C virus was shed in 16 (27%) of semen specimens from 11 (33%) of the men. Median HCV viral load (VL) in semen was 1.49 log10 IU/mL. Hepatitis C virus VL in blood was significantly higher at the time of HCV shedding in semen than when HCV shedding in semen was not detected (P = .002). Furthermore, there was a significant correlation between the HCV VL in blood and semen overall (rs = 0.41; P = .001), and in the subgroup with recent HCV infection (rs = 0.37; P = .02), but not in the subgroup with chronic HCV infection (rs = 0.34; P = .1). Conclusions. One third of HIV-infected MSM coinfected with HCV shed HCV into their semen. Based on the HCV VL in semen in this study, an average ejaculate would deliver up to 6630 IU of virus into the rectum of the receptive partner. Therefore, our data strongly support that condoms should be used during anal intercourse among MSM to prevent transmission of HCV. PMID:27186582

  1. Shedding of Hepatitis C Virus in Semen of Human Immunodeficiency Virus-Infected Men.

    PubMed

    Turner, Samuel S; Gianella, Sara; Yip, Marcus J-S; van Seggelen, Wouter O; Gillies, Robert D; Foster, Andrew L; Barbati, Zachary R; Smith, Davey M; Fierer, Daniel S

    2016-03-01

    Background.  The epidemic of sexually transmitted hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) has been documented for over a decade. Despite this, there is no consensus as to the risk factors for sexual acquisition of HCV in these men. Methods.  We obtained paired semen and blood samples at 2-week intervals from HIV-infected MSM with recent and chronic HCV infection and quantified HCV in semen. Results.  Hepatitis C virus was quantified in 59 semen specimens from 33 men. Hepatitis C virus was shed in 16 (27%) of semen specimens from 11 (33%) of the men. Median HCV viral load (VL) in semen was 1.49 log10 IU/mL. Hepatitis C virus VL in blood was significantly higher at the time of HCV shedding in semen than when HCV shedding in semen was not detected (P = .002). Furthermore, there was a significant correlation between the HCV VL in blood and semen overall (rs = 0.41; P = .001), and in the subgroup with recent HCV infection (rs = 0.37; P = .02), but not in the subgroup with chronic HCV infection (rs = 0.34; P = .1). Conclusions.  One third of HIV-infected MSM coinfected with HCV shed HCV into their semen. Based on the HCV VL in semen in this study, an average ejaculate would deliver up to 6630 IU of virus into the rectum of the receptive partner. Therefore, our data strongly support that condoms should be used during anal intercourse among MSM to prevent transmission of HCV. PMID:27186582

  2. A DNA Virus of Drosophila

    PubMed Central

    Unckless, Robert L.

    2011-01-01

    Little is known about the viruses infecting most species. Even in groups as well-studied as Drosophila, only a handful of viruses have been well-characterized. A viral metagenomic approach was used to explore viral diversity in 83 wild-caught Drosophila innubila, a mushroom feeding member of the quinaria group. A single fly that was injected with, and died from, Drosophila C Virus (DCV) was added to the sample as a control. Two-thirds of reads in the infected sample had DCV as the best BLAST hit, suggesting that the protocol developed is highly sensitive. In addition to the DCV hits, several sequences had Oryctes rhinoceros Nudivirus, a double-stranded DNA virus, as a best BLAST hit. The virus associated with these sequences was termed Drosophila innubila Nudivirus (DiNV). PCR screens of natural populations showed that DiNV was both common and widespread taxonomically and geographically. Electron microscopy confirms the presence of virions in fly fecal material similar in structure to other described Nudiviruses. In 2 species, D. innubila and D. falleni, the virus is associated with a severe (∼80–90%) loss of fecundity and significantly decreased lifespan. PMID:22053195

  3. Highly efficient inhibition of human immunodeficiency virus type 1 reverse transcriptase by aptamers functionalized gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Shiang, Yen-Chun; Ou, Chung-Mao; Chen, Shih-Ju; Ou, Ting-Yu; Lin, Han-Jia; Huang, Chih-Ching; Chang, Huan-Tsung

    2013-03-01

    We have developed aptamer (Apt)-conjugated gold nanoparticles (Apt-Au NPs, 13 nm in diameter) as highly effective inhibitors for human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT). Two Apts, RT1t49 (Aptpol) and ODN 93 (AptRH), which recognize the polymerase and RNase H regions of HIV-1 RT, are used to conjugate Au NPs to prepare Aptpol-Au NPs and AptRH-Au NPs, respectively. In addition to DNA sequence, the surface density of the aptamers on Au NPs (nApt-Au NPs; n is the number of aptamer molecules on each Au NP) and the linker length number (Tm; m is the base number of the deoxythymidine linker) between the aptamer and Au NPs play important roles in determining their inhibition activity. A HIV-lentiviral vector-based antiviral assay has been applied to determine the inhibitory effect of aptamers or Apt-Au NPs on the early stages of their replication cycle. The nuclease-stable G-quadruplex structure of 40AptRH-T45-Au NPs shows inhibitory efficiency in the retroviral replication cycle with a decreasing infectivity (40.2%).We have developed aptamer (Apt)-conjugated gold nanoparticles (Apt-Au NPs, 13 nm in diameter) as highly effective inhibitors for human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT). Two Apts, RT1t49 (Aptpol) and ODN 93 (AptRH), which recognize the polymerase and RNase H regions of HIV-1 RT, are used to conjugate Au NPs to prepare Aptpol-Au NPs and AptRH-Au NPs, respectively. In addition to DNA sequence, the surface density of the aptamers on Au NPs (nApt-Au NPs; n is the number of aptamer molecules on each Au NP) and the linker length number (Tm; m is the base number of the deoxythymidine linker) between the aptamer and Au NPs play important roles in determining their inhibition activity. A HIV-lentiviral vector-based antiviral assay has been applied to determine the inhibitory effect of aptamers or Apt-Au NPs on the early stages of their replication cycle. The nuclease-stable G-quadruplex structure of 40AptRH-T45

  4. Role of Feline Immunodeficiency Virus in Lymphomagenesis--Going Alone or Colluding?

    PubMed

    Kaye, Sarah; Wang, Wenqi; Miller, Craig; McLuckie, Alicia; Beatty, Julia A; Grant, Chris K; VandeWoude, Sue; Bielefeldt-Ohmann, Helle

    2016-01-01

    Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of domestic and nondomestic feline species. Infection in domestic cats leads to immune dysfunction via mechanisms similar to those caused by human immunodeficiency virus (HIV) and, as such, is a valuable natural animal model for acquired immunodeficiency syndrome (AIDS) in humans. An association between FIV and an increased incidence of neoplasia has long been recognized, with frequencies of up to 20% in FIV-positive cats recorded in some studies. This is similar to the rate of neoplasia seen in HIV-positive individuals, and in both species neoplasia typically requires several years to arise. The most frequently reported type of neoplasia associated with FIV infection is lymphoma. Here we review the possible mechanisms involved in FIV lymphomagenesis, including the possible involvement of coinfections, notably those with gamma-herpesviruses.

  5. Kinetics and inhibition of reverse transcriptase from human and simian immunodeficiency viruses.

    PubMed Central

    Wu, J C; Chernow, M; Boehme, R E; Suttmann, R T; McRoberts, M J; Prisbe, E J; Matthews, T R; Marx, P A; Chuang, R Y; Chen, M S

    1988-01-01

    Reverse transcriptase from the simian immunodeficiency virus (SIV) was found to have kinetic behavior similar to that of enzyme from the human immunodeficiency virus (HIV). Michaelis constants for the substrates TTP and dGTP and inhibition constants for the inhibitors 3'-azido-3'-deoxythymidine 5'-triphosphate, 2',3'-dideoxythymidine 5'-triphosphate, and 2'-3'-dideoxyguanosine 5'-triphosphate were obtained for SIV reverse transcriptase and were found to be similar to the corresponding values for HIV reverse transcriptase. Thus, the interaction of SIV reverse transcriptase with nucleotide analogs appears to be indistinguishable from that of the HIV enzyme, suggesting that SIV/simian acquired immunodeficiency syndrome (SAIDS) is a potentially good model of AIDS. PMID:2469388

  6. SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates.

    PubMed

    Lahouassa, Hichem; Daddacha, Waaqo; Hofmann, Henning; Ayinde, Diana; Logue, Eric C; Dragin, Loïc; Bloch, Nicolin; Maudet, Claire; Bertrand, Matthieu; Gramberg, Thomas; Pancino, Gianfranco; Priet, Stéphane; Canard, Bruno; Laguette, Nadine; Benkirane, Monsef; Transy, Catherine; Landau, Nathaniel R; Kim, Baek; Margottin-Goguet, Florence

    2012-03-01

    SAMHD1 restricts the infection of dendritic and other myeloid cells by human immunodeficiency virus type 1 (HIV-1), but in lentiviruses of the simian immunodeficiency virus of sooty mangabey (SIVsm)-HIV-2 lineage, SAMHD1 is counteracted by the virion-packaged accessory protein Vpx. Here we found that SAMHD1 restricted infection by hydrolyzing intracellular deoxynucleoside triphosphates (dNTPs), lowering their concentrations to below those required for the synthesis of the viral DNA by reverse transcriptase (RT). SAMHD1-mediated restriction was alleviated by the addition of exogenous deoxynucleosides. An HIV-1 with a mutant RT with low affinity for dNTPs was particularly sensitive to SAMHD1-mediated restriction. Vpx prevented the SAMHD1-mediated decrease in dNTP concentration and induced the degradation of human and rhesus macaque SAMHD1 but had no effect on mouse SAMHD1. Nucleotide-pool depletion could be a general mechanism for protecting cells from infectious agents that replicate through a DNA intermediate. PMID:22327569

  7. An 11-kDa form of human immunodeficiency virus protease expressed in Escherichia coli is sufficient for enzymatic activity.

    PubMed Central

    Graves, M C; Lim, J J; Heimer, E P; Kramer, R A

    1988-01-01

    In order to define the protease domain of human immunodeficiency virus 1, various regions of the pol open reading frame were cloned and expressed in Escherichia coli. Antiserum directed against the conserved retroviral protease active site was used to identify pol precursor and processed species containing the presumed protease domain. The smallest product that accumulates is about 11 kDa as measured by NaDodSO4/PAGE. This size agrees with that predicted from the presence in this region of two Phe-Pro sequences, which is one of the cleavage sites recognized by HIV protease. DNA encoding only the predicted 11-kDa protein was cloned, bypassing the need for autoprocessing, and the protein was expressed to a high level in E. coli. This form is active as demonstrated by its ability to specifically cleave protease-deficient pol protein in vivo in E. coli. Extracts of E. coli containing the 11-kDa protease also process human immunodeficiency virus gag substrates in vitro. These results demonstrate that the 11-kDa protease is sufficient for enzymatic activity and are consistent with a major role for this form in virus maturation. Images PMID:3282230

  8. Intracellular proteins of feline immunodeficiency virus and their antigenic relationship with equine infectious anaemia virus proteins.

    PubMed

    Egberink, H F; Ederveen, J; Montelaro, R C; Pedersen, N C; Horzinek, M C; Koolen, M J

    1990-03-01

    Feline immunodeficiency virus (FIV) grown in cat lymphocyte and thymocyte cultures was labelled with L-[35S]methionine or [3H]glucosamine and virus-coded proteins were identified using immunoprecipitation. Polypeptides with apparent Mr values of 15K, 24K, 43K, 50K, 120K and 160K were detected. An additional polypeptide of 10K was detected by Western blot analysis. The two highest Mr species sometimes appeared as one band, of which only the 120K polypeptide was glycosylated. In the presence of tunicamycin gp120 was no longer detectable and a non-glycosylated precursor of 75K was found instead. Pulse-chase experiments suggested that the smaller polypeptides p24 and p15 are cleavage products of both p160 and p50. Western blot analysis using a rabbit serum directed against p26 of equine infectious anaemia virus (EIAV) and an anti-EIAV horse serum from a field case of infection revealed a cross-reactivity with p24 of FIV. Cat sera collected late after experimental FIV infection recognized p26 of EIAV, indicating a reciprocal cross-reactivity. PMID:1690264

  9. Human immunodeficiency virus type 1 infection of mature CD3hiCD8+ thymocytes.

    PubMed Central

    Lee, S; Goldstein, H; Baseler, M; Adelsberger, J; Golding, H

    1997-01-01

    Although CD4+ cells are the primary targets of human immunodeficiency virus type 1 (HIV-1) infection, earlier reports have suggested that intrathymic infection of CD8+ cells may occur. However, it was unclear whether HIV-1-infected CD8+ thymocytes were truly mature single-positive (SP) cells. In the present study, SCID mice implanted with human fetal thymus and liver tissues (SCID-hu mice) were infected with three primary isolates of HIV-1 and infected thymocytes were analyzed to assess maturational status. After intra-implant or intraperitoneal injection with HIV-1, thymocytes were sorted by three-color flow cytometric analysis into mature populations of CD3hiCD4+ and CD3hiCD8+ SP cells of > 99% purity (< 0.3% CD4-containing cells in the CD8+ population). The presence of HIV-1 provirus in the sorted thymocyte populations was determined by quantitative PCR. A fraction of mature CD3hiCD8+ thymocytes contained HIV-1 proviral DNA, and evidence of viral mRNA transcription in these cells was demonstrated by in situ hybridization. In contrast, when uninfected CD3hiCD8+ thymocytes were cocultured with HIV-1-infected CD4+ thymocytes, no evidence of productive HIV-1 infection was detected. Thus, HIV-1 infection of CD8+ thymocytes in the SCID-hu mouse does not occur by direct contact with the virus. Rather, cell surface CD4 is required; therefore, precursor cells are the likely primary target of HIV-1 infection in the thymus. During ontogeny, some of these infected cells continue their differentiation into mature CD8+ SP thymocytes that contain proviral DNA and express viral RNA. PMID:9261389

  10. Feline leukemia virus and feline immunodeficiency virus infections in a cat with lymphoma.

    PubMed

    Shelton, G H; McKim, K D; Cooley, P L; Dice, P F; Russell, R G; Grant, C K

    1989-01-15

    Lymphoma was diagnosed in a 7-year-old domestic cat found to be infected with FeLV and feline immunodeficiency virus (FIV). The cat was affected by chronic disorders suggestive of immunosuppression, including gingivitis, periodontitis, keratitis, and abscesses. Despite treatment, peripheral keratitis of the left eye progressed, resulting in uveitis, chronic glaucoma, and eventual corneal rupture. Microscopic retinal and optic disk pathologic processes also were suspected. Abnormal jaw movements that were believed to be indicative of neurologic disease were observed. Approximately 17 months later, the cat developed generalized lymphadenopathy, hepatosplenomegaly, and bilateral renomegaly. Lymphoblastic lymphoma and glomerulonephritis were diagnosed histologically. Manganese- and magnesium-dependent reverse transcriptase activity were detected in supernatants from lymph node and spleen mononuclear cell cultures, suggesting T-lymphocyte infection with FeLV and FIV. PMID:2537274

  11. Effect of different donor cells on human immunodeficiency virus type 1 replication and selection in vitro.

    PubMed Central

    Spira, A I; Ho, D D

    1995-01-01

    We sought to determine the effects of different host cells on human immunodeficiency virus type 1 (HIV-1) infection in vitro. First, 17 primary viruses of various phenotypes were examined for replicative capacity in peripheral blood mononuclear cells (PBMC) from 10 healthy donors. While the range of infection was variable over a 40-fold range, it was substantially less than that previously reported (L. M. Williams and M. W. Cloyd, Virology 184:723-728, 1991). In particular, no donor cells demonstrated total resistance to HIV-1 infection. We next cocultured PBMC from an HIV-1-infected patient with stimulated PBMC from three healthy donors to determine the effect of host cells on selection for a particular HIV-1 quasispecies. By using DNA sequencing, it was found that the dominant quasispecies (AD30-15) after culture was nearly identical in the cells of different donors. Furthermore, after 6 months in vivo, the patient developed a dominant proviral population in PBMC that was most closely related to the quasispecies preferentially selected in vitro, although this quasispecies was only a minor fraction of the sequences present earlier in PBMC. In subsequent biological characterizations, it was found that AD30-15 grew much better in PBMC and macrophages than did other related quasispecies. Hence, we conclude that the primary mechanism of in vitro selection for a particular HIV-1 variant in this case is mediated by the phenotypic properties of the virus and is less dependent on host cell origin. The findings reported here have important practical implications for studies of HIV-1 replication in primary cells derived from healthy donors. PMID:7983738

  12. Molecular Epidemiology of Simian Immunodeficiency Virus Infection in Wild-Living Gorillas▿

    PubMed Central

    Neel, Cécile; Etienne, Lucie; Li, Yingying; Takehisa, Jun; Rudicell, Rebecca S.; Ndong Bass, Innocent; Moudindo, Joseph; Mebenga, Aimé; Esteban, Amandine; Van Heuverswyn, Fran; Liegeois, Florian; Kranzusch, Philip J.; Walsh, Peter D.; Sanz, Crickette M.; Morgan, David B.; Ndjango, Jean-Bosco N.; Plantier, Jean-Christophe; Locatelli, Sabrina; Gonder, Mary K.; Leendertz, Fabian H.; Boesch, Christophe; Todd, Angelique; Delaporte, Eric; Mpoudi-Ngole, Eitel; Hahn, Beatrice H.; Peeters, Martine

    2010-01-01

    Chimpanzees and gorillas are the only nonhuman primates known to harbor viruses closely related to HIV-1. Phylogenetic analyses showed that gorillas acquired the simian immunodeficiency virus SIVgor from chimpanzees, and viruses from the SIVcpz/SIVgor lineage have been transmitted to humans on at least four occasions, leading to HIV-1 groups M, N, O, and P. To determine the geographic distribution, prevalence, and species association of SIVgor, we conducted a comprehensive molecular epidemiological survey of wild gorillas in Central Africa. Gorilla fecal samples were collected in the range of western lowland gorillas (n = 2,367) and eastern Grauer gorillas (n = 183) and tested for SIVgor antibodies and nucleic acids. SIVgor antibody-positive samples were identified at 2 sites in Cameroon, with no evidence of infection at 19 other sites, including 3 in the range of the Eastern gorillas. In Cameroon, based on DNA and microsatellite analyses of a subset of samples, we estimated the prevalence of SIVgor to be 1.6% (range, 0% to 4.6%), which is significantly lower than the prevalence of SIVcpzPtt in chimpanzees (5.9%; range, 0% to 32%). All newly identified SIVgor strains formed a monophyletic lineage within the SIVcpz radiation, closely related to HIV-1 groups O and P, and clustered according to their field site of origin. At one site, there was evidence for intergroup transmission and a high intragroup prevalence. These isolated hot spots of SIVgor-infected gorilla communities could serve as a source for human infection. The overall low prevalence and sporadic distribution of SIVgor could suggest a decline of SIVgor in wild populations, but it cannot be excluded that SIVgor is still more prevalent in other parts of the geographical range of gorillas. PMID:19906908

  13. Simple in vitro methods for titrating feline immunodeficiency virus (FIV) and FIV neutralizing antibodies.

    PubMed

    Tozzini, F; Matteucci, D; Bandecchi, P; Baldinotti, F; Poli, A; Pistello, M; Siebelink, K H; Ceccherini-Nelli, L; Bendinelli, M

    1992-06-01

    The feline immunodeficiency virus (FIV) readily produced syncytia in Crandell feline kidney (CrFK) cells adapted to a medium containing 0.5% fetal calf serum, a variety of growth factors and other supplements. This finding has been exploited to develop simple and sensitive virus titration and neutralization assays. High titre neutralizing antibodies were detected in cats infected naturally and experimentally with FIV, but not in uninfected animals.

  14. [Analysis of genetic recombination between human immunodeficiency virus type 1 (HIV-1) and HIV-2].

    PubMed

    Motomura, Kazushi

    2009-03-01

    It is estimated that one million people are dually infected with Human Immunodeficiency Virus type-I (HIV-1) and type-II (HIV-2) in West Africa and parts of India. HIV-1 and HIV-2 use the same receptor and coreceptors for entry into cells, and thus target the same cell populations in the host. Additionally, we first examined whether RNAs from HIV-1 and HIV-2 can be copackaged into the same virion. Therefore these properties suggest that in the dually infected population, it is likely that some cells can be infected by both HIV-1 and HIV-2, thereby providing opportunities for these two viruses to interact with each other. We constructed recombination assay system for measurement recombination frequencies and analyzed recombination rate between HIV-1 and HIV-2. We used modified near-full-length viruses that each contained a green fluorescent protein gene (gfp) with a different inactivating mutation. Thus, a functional gfp could be reconstituted via recombination, which was used to detect copackaging of HIV-1 and HIV-2 RNAs. In this study, approximately 0.2% of infection events generated the GFP phenotype. Therefore, the appearance of the GFP+ phenotype in the current system is approximately 35-fold lower than that between two homologous HIV-1 or HIV-2 viruses. We then mapped the general structures of the recombinant viruses and characterized the recombination junctions by DNA sequencing. We observed several different recombination patterns including those only had crossovers in gfp. The most common hybrid genomes had heterologous LTRs. Although infrequent, crossovers were also identified in the viral sequences. Such chimeric HIV-1 and HIV-2 viruses have yet to be observed in the infected population. It is unclear whether the lack of observed chimeras is due to the divergence between HIV-1 and HIV-2 being too great for such an event to occur, or whether such events could occur but have not yet been observed. Given the number of coinfected people, the potential for

  15. Statin Effects to Reduce Hepatosteatosis as Measured by Computed Tomography in Patients With Human Immunodeficiency Virus

    PubMed Central

    Lo, Janet; Lu, Michael T.; Kim, Elli A.; Nou, Eric; Hallett, Travis R.; Park, Jakob; Hoffmann, Udo; Grinspoon, Steven K.

    2016-01-01

    Hepatosteatosis is highly prevalent among patients living with human immunodeficiency virus. In a 1-year, randomized, double-blind trial of atorvastatin or placebo, atorvastatin increased liver/spleen ratio among patients with nonalcoholic fatty liver disease, indicating a reduction in hepatosteatosis. This reduction in hepatosteatosis is associated with reduction in low-density lipoprotein cholesterol with statin therapy. PMID:27419149

  16. Evaluation of Serum Creatinine Changes With Integrase Inhibitor Use in Human Immunodeficiency Virus-1 Infected Adults

    PubMed Central

    Lindeman, Tara A.; Duggan, Joan M.; Sahloff, Eric G.

    2016-01-01

    This retrospective chart review evaluated changes in serum creatinine and creatinine clearance (CrCl) after initiation of an integrase inhibitor (INSTI)-based regimen as initial treatment in human immunodeficiency virus-infected adults. Serum creatinine and CrCl changes were similar to those seen in clinical trials for INSTIs. No renal-related serious adverse events or discontinuations occurred. PMID:27092314

  17. Human Immunodeficiency Virus (HIV) Testing and False Disclosures in Heterosexual College Students

    ERIC Educational Resources Information Center

    Marelich, William D.; Clark, Tonya

    2004-01-01

    The authors assessed factors that motivate individuals to report negative human immunodeficiency virus (HIV) antibody test results, although they had never been tested. In particular, they investigated sexual intimacy motives associated with the needs for affiliation, sex, and dominance as contributing factors for faulty disclosures. Participants…

  18. Case Study: Delirium in an Adolescent Girl with Human Immunodeficiency Virus-Associated Dementia

    ERIC Educational Resources Information Center

    Scharko, Alexander M.; Baker, Eva H.; Kothari, Priti; Khattak, Hina; Lancaster, Duniya

    2006-01-01

    Delirium and human immunodeficiency virus (HIV)-associated dementia are well recognized neuropsychiatric consequences of HIV infection in adults. Almost nothing is known regarding the management of delirium in HIV-infected children and adolescents. HIV-related progressive encephalopathy is thought to represent the pediatric form of HIV-associated…

  19. Prevalence of Human Immunodeficiency Virus Testing and Associated Risk Factors in College Students

    ERIC Educational Resources Information Center

    Dennison, Olivia; Wu, Qishan; Ickes, Melinda

    2014-01-01

    Objective: This study documents the prevalence of human immunodeficiency virus (HIV) testing in a sample of college students and examines associated demographic and behavioral characteristics. Participants: College students aged 18 or older were randomly selected to participate in a health behavior survey at a southeastern university in September…

  20. Association of human immunodeficiency virus-induced immunosuppression with human papillomavirus infection and cervical intraepithelial neoplasia.

    PubMed

    Henry, M J; Stanley, M W; Cruikshank, S; Carson, L

    1989-02-01

    Human papillomavirus infection plays an important causal role in cervical intraepithelial neoplasia and carcinoma. The rate of infection with human papillomavirus as well as the incidence of cervical intraepithelial neoplasia and carcinoma are increased in immunosuppressed patients. We report a possible association between infection with human immunodeficiency virus and cervical intraepithelial neoplasia with human papillomavirus infection.

  1. Statin Effects to Reduce Hepatosteatosis as Measured by Computed Tomography in Patients With Human Immunodeficiency Virus.

    PubMed

    Lo, Janet; Lu, Michael T; Kim, Elli A; Nou, Eric; Hallett, Travis R; Park, Jakob; Hoffmann, Udo; Grinspoon, Steven K

    2016-04-01

    Hepatosteatosis is highly prevalent among patients living with human immunodeficiency virus. In a 1-year, randomized, double-blind trial of atorvastatin or placebo, atorvastatin increased liver/spleen ratio among patients with nonalcoholic fatty liver disease, indicating a reduction in hepatosteatosis. This reduction in hepatosteatosis is associated with reduction in low-density lipoprotein cholesterol with statin therapy. PMID:27419149

  2. In Vivo Replication Capacity Rather Than In Vitro Macrophage Tropism Predicts Efficiency of Vaginal Transmission of Simian Immunodeficiency Virus or Simian/Human Immunodeficiency Virus in Rhesus Macaques

    PubMed Central

    Miller, Christopher J.; Marthas, Marta; Greenier, Jennifer; Lu, Ding; Dailey, Peter J.; Lu, Yichen

    1998-01-01

    We used the rhesus macaque model of heterosexual human immunodeficiency virus (HIV) transmission to test the hypothesis that in vitro measures of macrophage tropism predict the ability of a primate lentivirus to initiate a systemic infection after intravaginal inoculation. A single atraumatic intravaginal inoculation with a T-cell-tropic molecular clone of simian immunodeficiency virus (SIV), SIVmac239, or a dualtropic recombinant molecular clone of SIV, SIVmac239/1A11/239, or uncloned dualtropic SIVmac251 or uncloned dualtropic simian/human immunodeficiency virus (SHIV) 89.6-PD produced systemic infection in all rhesus macaques tested. However, vaginal inoculation with a dualtropic molecular clone of SIV, SIVmac1A11, resulted in transient viremia in one of two rhesus macaques. It has previously been shown that 12 intravaginal inoculations with SIVmac1A11 resulted in infection of one of five rhesus macaques (M. L. Marthas, C. J. Miller, S. Sutjipto, J. Higgins, J. Torten, B. L. Lohman, R. E. Unger, H. Kiyono, J. R. McGhee, P. A. Marx, and N. C. Pedersen, J. Med. Primatol. 21:99–107, 1992). In addition, SHIV HXBc2, which replicates in monkey macrophages, does not infect rhesus macaques following multiple vaginal inoculations, while T-cell-tropic SHIV 89.6 does (Y. Lu, P. B. Brosio, M. Lafaile, J. Li, R. G. Collman, J. Sodroski, and C. J. Miller, J. Virol. 70:3045–3050, 1996). These results demonstrate that in vitro measures of macrophage tropism do not predict if a SIV or SHIV will produce systemic infection after intravaginal inoculation of rhesus macaques. However, we did find that the level to which these viruses replicate in vivo after intravenous inoculation predicts the outcome of intravaginal inoculation with each virus. PMID:9525652

  3. Genetic diversity of human immunodeficiency virus type 2: evidence for distinct sequence subtypes with differences in virus biology.

    PubMed Central

    Gao, F; Yue, L; Robertson, D L; Hill, S C; Hui, H; Biggar, R J; Neequaye, A E; Whelan, T M; Ho, D D; Shaw, G M

    1994-01-01

    The virulence properties of human immunodeficiency virus type 2 (HIV-2) are known to vary significantly and to range from relative attenuation in certain individuals to high-level pathogenicity in others. These differences in clinical manifestations may, at least in part, be determined by genetic differences among infecting virus strains. Evaluation of the full spectrum of HIV-2 genetic diversity is thus a necessary first step towards understanding its molecular epidemiology, natural history of infection, and biological diversity. In this study, we have used nested PCR techniques to amplify viral sequences from the DNA of uncultured peripheral blood mononuclear cells from 12 patients with HIV-2 seroreactivity. Sequence analysis of four nonoverlapping genomic regions allowed a comprehensive analysis of HIV-2 phylogeny. The results revealed (i) the existence of five distinct and roughly equidistant evolutionary lineages of HIV-2 which, by analogy with HIV-1, have been termed sequence subtypes A to E; (ii) evidence for a mosaic HIV-2 genome, indicating that coinfection with genetically divergent strains and recombination can occur in HIV-2-infected individuals; and (iii) evidence supporting the conclusion that some of the HIV-2 subtypes may have arisen from independent introductions of genetically diverse sooty mangabey viruses into the human population. Importantly, only a subset of HIV-2 strains replicated in culture: all subtype A viruses grew to high titers, but attempts to isolate representatives of subtypes C, D, and E, as well as the majority of subtype B viruses, remained unsuccessful. Infection with all five viral subtypes was detectable by commercially available serological (Western immunoblot) assays, despite intersubtype sequence differences of up to 25% in the gag, pol, and env regions. These results indicate that the genetic and biological diversity of HIV-2 is far greater than previously appreciated and suggest that there may be subtype

  4. Transcription factor binding sites downstream of the human immunodeficiency virus type 1 transcription start site are important for virus infectivity.

    PubMed Central

    Van Lint, C; Amella, C A; Emiliani, S; John, M; Jie, T; Verdin, E

    1997-01-01

    When transcriptionally active, the human immunodeficiency virus (HIV) promoter contains a nucleosome-free region encompassing both the promoter/enhancer region and a large region (255 nucleotides [nt]) downstream of the transcription start site. We have previously identified new binding sites for transcription factors downstream of the transcription start site (nt 465 to 720): three AP-1 sites (I, II, and III), an AP3-like motif (AP3-L), a downstream binding factor (DBF) site, and juxtaposed Sp1 sites. Here, we show that the DBF site is an interferon-responsive factor (IRF) binding site and that the AP3-L motif binds the T-cell-specific factor NF-AT. Mutations that abolish the binding of each factor to its cognate site are introduced in an infectious HIV-1 molecular clone to study their effect on HIV-1 transcription and replication. Individual mutation of the DBF or AP3-L site as well as the double mutation AP-1(III)/AP3-L did not affect HIV-1 replication compared to that of the wild-type virus. In contrast, proviruses carrying mutations in the Sp1 sites were totally defective in terms of replication. Virus production occurred with slightly delayed kinetics for viruses containing combined mutations in the AP-1(III), AP3-L, and DBF sites and in the AP3-L and DBF-sites, whereas viruses mutated in the AP-1(I,II,III) and AP3-L sites and in the AP-1(I,II,III), AP3-L, and DBF sites exhibited a severely defective replicative phenotype. No RNA-packaging defect could be measured for any of the mutant viruses as determined by quantification of their HIV genomic RNA. Measurement of the transcriptional activity of the HIV-1 promoter after transient transfection of the HIV-1 provirus DNA or of long terminal repeat-luciferase constructs showed a positive correlation between the transcriptional and the replication defects for most mutants. PMID:9223506

  5. A Single-Nucleotide Synonymous Mutation in the gag Gene Controlling Human Immunodeficiency Virus Type 1 Virion Production▿

    PubMed Central

    Hamano, Takaichi; Matsuo, Kazuhiro; Hibi, Yurina; Victoriano, Ann Florence B.; Takahashi, Naoko; Mabuchi, Yosio; Soji, Tsuyoshi; Irie, Shinji; Sawanpanyalert, Pathom; Yanai, Hideki; Hara, Takashi; Yamazaki, Shudo; Yamamoto, Naoki; Okamoto, Takashi

    2007-01-01

    Viral factors as well as host ones play major roles in the disease progression of human immunodeficiency virus type 1 (HIV-1) infection. We have examined cytotoxic T-lymphocyte activity and HIV-1 DNA PCR results of 312 high-risk seronegative drug users in northern Thailand and identified four seronegative cases positive for both assays. Furthermore, we have identified a synonymous mutation in nucleotide position 75 of the gag p17 gene (A426G) of HIV-1 that belongs to the CRF01_AE virus circulating in Thailand. The replication-competent HIV-1 clone containing the A426G mutation demonstrated a dramatic reduction of virion production and perturbation of viral morphogenesis without affecting viral protein synthesis in cells. PMID:17121798

  6. A Naturally Occurring Domestic Cat APOBEC3 Variant Confers Resistance to Feline Immunodeficiency Virus Infection

    PubMed Central

    Yoshikawa, Rokusuke; Izumi, Taisuke; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Ren, Fengrong; Carpenter, Michael A.; Ikeda, Terumasa; Münk, Carsten; Harris, Reuben S.; Miyazawa, Takayuki; Koyanagi, Yoshio

    2015-01-01

    ABSTRACT Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) DNA cytosine deaminases can be incorporated into progeny virions and inhibit lentiviral replication. On the other hand, viral infectivity factor (Vif) of lentiviruses antagonizes A3-mediated antiviral activities by degrading A3 proteins. It is known that domestic cat (Felis catus) APOBEC3Z3 (A3Z3), the ortholog of human APOBEC3H, potently suppresses the infectivity of vif-defective feline immunodeficiency virus (FIV). Although a recent report has shown that domestic cat encodes 7 haplotypes (hap I to hap VII) of A3Z3, the relevance of A3Z3 polymorphism in domestic cats with FIV Vif has not yet been addressed. In this study, we demonstrated that these feline A3Z3 variants suppress vif-defective FIV infectivity. We also revealed that codon 65 of feline A3Z3 is a positively selected site and that A3Z3 hap V is subject to positive selection during evolution. It is particularly noteworthy that feline A3Z3 hap V is resistant to FIV Vif-mediated degradation and still inhibits vif-proficient viral infection. Moreover, the side chain size, but not the hydrophobicity, of the amino acid at position 65 determines the resistance to FIV Vif-mediated degradation. Furthermore, phylogenetic analyses have led to the inference that feline A3Z3 hap V emerged approximately 60,000 years ago. Taken together, these findings suggest that feline A3Z3 hap V may have been selected for escape from an ancestral FIV. This is the first evidence for an evolutionary “arms race” between the domestic cat and its cognate lentivirus. IMPORTANCE Gene diversity and selective pressure are intriguing topics in the field of evolutionary biology. A direct interaction between a cellular protein and a viral protein can precipitate an evolutionary arms race between host and virus. One example is primate APOBEC3G, which potently restricts the replication of primate lentiviruses (e.g., human immunodeficiency virus type 1

  7. Recombination in Eukaryotic Single Stranded DNA Viruses

    PubMed Central

    Martin, Darren P.; Biagini, Philippe; Lefeuvre, Pierre; Golden, Michael; Roumagnac, Philippe; Varsani, Arvind

    2011-01-01

    Although single stranded (ss) DNA viruses that infect humans and their domesticated animals do not generally cause major diseases, the arthropod borne ssDNA viruses of plants do, and as a result seriously constrain food production in most temperate regions of the world. Besides the well known plant and animal-infecting ssDNA viruses, it has recently become apparent through metagenomic surveys of ssDNA molecules that there also exist large numbers of other diverse ssDNA viruses within almost all terrestrial and aquatic environments. The host ranges of these viruses probably span the tree of life and they are likely to be important components of global ecosystems. Various lines of evidence suggest that a pivotal evolutionary process during the generation of this global ssDNA virus diversity has probably been genetic recombination. High rates of homologous recombination, non-homologous recombination and genome component reassortment are known to occur within and between various different ssDNA virus species and we look here at the various roles that these different types of recombination may play, both in the day-to-day biology, and in the longer term evolution, of these viruses. We specifically focus on the ecological, biochemical and selective factors underlying patterns of genetic exchange detectable amongst the ssDNA viruses and discuss how these should all be considered when assessing the adaptive value of recombination during ssDNA virus evolution. PMID:21994803

  8. Frequent perinatal transmission of feline immunodeficiency virus by chronically infected cats.

    PubMed Central

    O'Neil, L L; Burkhard, M J; Hoover, E A

    1996-01-01

    Vertical transmission of feline immunodeficiency virus (FIV) was studied in cats infected with either of two FIV clinical isolates (FIV-B-2542 or FIV-AB-2771) prior to breeding and conception. Queens infected 4 to 30 months (mean = 14 months) prior to conception transmitted FIV to 59 of 83 (71%) kittens; 50.6% were virus positive on the day of birth. To examine potential routes of FIV transmission from mother to offspring, kittens were delivered via either vaginal or cesarean birth and nursed by either their virus-infected natural mothers or uninfected surrogate mothers. Comparison of FIV infection rates at birth with those at 6 months of age in kittens delivered by cesarean and surrogate raised demonstrated that late in utero transmission occurred in approximately 20% of kittens. Comparison of kittens nursed by FIV mothers with those by uninfected surrogate mothers demonstrated a 13.5% increase in infection rate of kittens exposed to milk-borne virus. Isolation of virus from 40% of maternal vaginal wash samples and the slightly greater infection rate in vaginally versus cesarean-delivered surrogate-nursed kittens suggested that intrapartum transmission may occur. In addition, we found that low maternal CD4 count (<200 cells per microl), longer duration of maternal infection (>15 months), and maternal symptoms of clinical immunodeficiency correlated with increased rates of mother-to-kitten FIV transmission, paralleling observations in human immunodeficiency virus-infected women. We conclude that FIV infection provides a model in which to explore aspects of human immunodeficiency virus vertical transmission and intervention difficult to address in human patients. PMID:8627764

  9. Efavirenz Therapy in Rhesus Macaques Infected with a Chimera of Simian Immunodeficiency Virus Containing Reverse Transcriptase from Human Immunodeficiency Virus Type 1

    PubMed Central

    Hofman, Michael J.; Higgins, Joanne; Matthews, Timothy B.; Pedersen, Niels C.; Tan, Chalet; Schinazi, Raymond F.; North, Thomas W.

    2004-01-01

    The specificity of nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) for the RT of human immunodeficiency virus type 1 (HIV-1) has prevented the use of simian immunodeficiency virus (SIV) in the study of NNRTIs and NNRTI-based highly active antiretroviral therapy. However, a SIV-HIV-1 chimera (RT-SHIV), in which the RT from SIVmac239 was replaced with the RT-encoding region from HIV-1, is susceptible to NNRTIs and is infectious to rhesus macaques. We have evaluated the antiviral activity of efavirenz against RT-SHIV and the emergence of efavirenz-resistant mutants in vitro and in vivo. RT-SHIV was susceptible to efavirenz with a mean effective concentration of 5.9 ± 4.5 nM, and RT-SHIV variants selected with efavirenz in cell culture displayed 600-fold-reduced susceptibility. The efavirenz-resistant mutants of RT-SHIV had mutations in RT similar to those of HIV-1 variants that were selected under similar conditions. Efavirenz monotherapy of RT-SHIV-infected macaques produced a 1.82-log-unit decrease in plasma viral-RNA levels after 1 week. The virus load rebounded within 3 weeks in one treated animal and more slowly in a second animal. Virus isolated from these two animals contained the K103N and Y188C or Y188L mutations. The RT-SHIV-rhesus macaque model may prove useful for studies of antiretroviral drug combinations that include efavirenz. PMID:15328115

  10. Linker insertion mutagenesis of the human immunodeficiency virus reverse transcriptase expressed in bacteria: definition of the minimal polymerase domain.

    PubMed Central

    Prasad, V R; Goff, S P

    1989-01-01

    A plasmid construct expressing the p66 version of the human immunodeficiency virus reverse transcriptase as a bacterial fusion protein was subjected to in vitro mutagenesis, and the resulting variant proteins were assayed to define the locations of the two major enzymatic activities. The DNA polymerase activity was localized to the N-terminal portion of the protein; mutations altering or eliminating the C-terminal portion had little or no effect on that activity. The results suggest that, in contrast with previous reports, the p51 subunit found in virions should exhibit DNA polymerase activity. Mutations in many parts of the protein eliminated RNase H activity, suggesting that several areas are needed for proper folding and generation of that activity. Images PMID:2470090

  11. Recursion-based depletion of human immunodeficiency virus-specific naive CD4(+) T cells may facilitate persistent viral replication and chronic viraemia leading to acquired immunodeficiency syndrome.

    PubMed

    Tsukamoto, Tetsuo; Yamamoto, Hiroyuki; Okada, Seiji; Matano, Tetsuro

    2016-09-01

    Although antiretroviral therapy has made human immunodeficiency virus (HIV) infection a controllable disease, it is still unclear how viral replication persists in untreated patients and causes CD4(+) T-cell depletion leading to acquired immunodeficiency syndrome (AIDS) in several years. Theorists tried to explain it with the diversity threshold theory in which accumulated mutations in the HIV genome make the virus so diverse that the immune system will no longer be able to recognize all the variants and fail to control the viraemia. Although the theory could apply to a number of cases, macaque AIDS models using simian immunodeficiency virus (SIV) have shown that failed viral control at the set point is not always associated with T-cell escape mutations. Moreover, even monkeys without a protective major histocompatibility complex (MHC) allele can contain replication of a super infected SIV following immunization with a live-attenuated SIV vaccine, while those animals are not capable of fighting primary SIV infection. Here we propose a recursion-based virus-specific naive CD4(+) T-cell depletion hypothesis through thinking on what may happen in individuals experiencing primary immunodeficiency virus infection. This could explain the mechanism for impairment of virus-specific immune response in the course of HIV infection.

  12. Recursion-based depletion of human immunodeficiency virus-specific naive CD4(+) T cells may facilitate persistent viral replication and chronic viraemia leading to acquired immunodeficiency syndrome.

    PubMed

    Tsukamoto, Tetsuo; Yamamoto, Hiroyuki; Okada, Seiji; Matano, Tetsuro

    2016-09-01

    Although antiretroviral therapy has made human immunodeficiency virus (HIV) infection a controllable disease, it is still unclear how viral replication persists in untreated patients and causes CD4(+) T-cell depletion leading to acquired immunodeficiency syndrome (AIDS) in several years. Theorists tried to explain it with the diversity threshold theory in which accumulated mutations in the HIV genome make the virus so diverse that the immune system will no longer be able to recognize all the variants and fail to control the viraemia. Although the theory could apply to a number of cases, macaque AIDS models using simian immunodeficiency virus (SIV) have shown that failed viral control at the set point is not always associated with T-cell escape mutations. Moreover, even monkeys without a protective major histocompatibility complex (MHC) allele can contain replication of a super infected SIV following immunization with a live-attenuated SIV vaccine, while those animals are not capable of fighting primary SIV infection. Here we propose a recursion-based virus-specific naive CD4(+) T-cell depletion hypothesis through thinking on what may happen in individuals experiencing primary immunodeficiency virus infection. This could explain the mechanism for impairment of virus-specific immune response in the course of HIV infection. PMID:27515208

  13. Pin1 liberates the human immunodeficiency virus type-1 (HIV-1): Must we stop it?

    PubMed

    Hou, Hai; Wang, Jing-Zhang; Liu, Bao-Guo; Zhang, Ting

    2015-07-01

    Acquired immune deficiency syndrome (AIDS) is mainly caused by the human immunodeficiency virus type-1 (HIV-1). To our knowledge, this is the first review focusing on the vital role of Pin1 in the infection of HIV-1 and the development of AIDS. We and others have demonstrated that Pin1, the only known cis-to-trans isomerase recognizing the pThr/pSer-Pro motifs in proteins, plays striking roles in several human diseases. Interestingly, recent evidence gradually indicates that Pin1 regulates several key steps of the life cycle of HIV-1, including the uncoating of the HIV-1 core, the reverse transcription of the RNA genome of HIV-1, and the integration of the HIV-1 cDNA into human chromosomes. Whereas inhibiting Pin1 suppresses all of these key steps and attenuates the replication of HIV-1, at the same time different PIN1 gene variants are correlated with the susceptibility to HIV-1 infection. Furthermore, Pin1 potentially promotes HIV-1 infection by activating multiple oncogenes and inactivating multiple tumor suppressors, extending the life span of HIV-infected cells. These descriptions suggest Pin1 as a promising therapeutic target for the prevention of HIV-1 and highlight the possibility of blocking the development of AIDS by Pin1 inhibitors.

  14. Slower evolution of human immunodeficiency virus type 1 quasispecies during progression to AIDS.

    PubMed Central

    Delwart, E L; Pan, H; Sheppard, H W; Wolpert, D; Neumann, A U; Korber, B; Mullins, J I

    1997-01-01

    The evolution of human immunodeficiency virus type 1 (HIV-1) quasispecies at the envelope gene was studied from the time of infection in 11 men who experienced different rates of CD4+ cell count decline and 6 men with unknown dates of infection by using DNA heteroduplex mobility assays. Quasispecies were genetically homogeneous near the time of seroconversion. Subsequently, slower proviral genetic diversification and higher plasma viremia correlated with rapid CD4+ cell count decline. Except for the fastest progressors to AIDS, highly diverse quasispecies developed in all subjects within 3 to 4 years. High quasispecies diversity was then maintained for years until again becoming more homogeneous in a subset of late-stage AIDS patients. Individuals who maintained high CD4+ cell counts showed continuous genetic turnover of their complex proviral quasispecies, while more closely related sets of variants were found in longitudinal samples of severely immunocompromised patients. The limited number of variants that grew out in short-term PBMC cocultures were rare in the uncultured proviral quasispecies of healthy, long-term infected individuals but more common in vivo in patients with low CD4+ cell counts. The slower evolution of HIV-1 observed during rapid progression to AIDS and in advanced patients may reflect ineffective host-mediated selection pressures on replicating quasispecies. PMID:9311829

  15. Molecular Characterization of the Human Immunodeficiency Virus Type 1 in Women and Their Vertically Infected Children.

    PubMed

    Vaz, Sara Nunes; Giovanetti, Marta; Rego, Filipe Ferreira de Almeida; Oliveira, Tulio de; Danaviah, Siva; Gonçalves, Maria Luiza Freire; Alcantara, Luiz Carlos Junior; Brites, Carlos

    2015-10-01

    Approximately 35 million people worldwide are infected with human immunodeficiency virus (HIV) around 3.2 million of whom are children under 15 years. Mother-to-child-transmission (MTCT) of HIV-1 accounts for 90% of all infections in children. Despite great advances in the prevention of MTCT in Brazil, children are still becoming infected. Samples from 19 HIV-1-infected families were collected. DNA was extracted and fragments from gag, pol, and env were amplified and sequenced directly. Phylogenetic reconstruction was performed. Drug resistance analyses were performed in pol and env sequences. We found 82.1% of subtype B and 17.9% of BF recombinants. A prevalence of 43.9% drug resistance-associated mutations in pol sequences was identified. Of the drug-naive children 33.3% presented at least one mutation related to protease inhibitor/nucleoside reverse transcriptase inhibitor/nonnucleoside reverse transcriptase inhibitor (PI/NRTI/NNRTI) resistance. The prevalence of transmitted drug resistance mutations was 4.9%. On env we found a low prevalence of HR1 (4.9%) and HR2 (14.6%) mutations. PMID:26200738

  16. Dried blood spots, valid screening for viral hepatitis and human immunodeficiency virus in real-life

    PubMed Central

    Mössner, Belinda K; Staugaard, Benjamin; Jensen, Janne; Lillevang, Søren Thue; Christensen, Peer B; Holm, Dorte Kinggaard

    2016-01-01

    AIM To detect chronic hepatitis B (CHB), chronic hepatitis C (CHC) and human immunodeficiency virus (HIV) infections in dried blood spot (DBS) and compare these samples to venous blood sampling in real-life. METHODS We included prospective patients with known viral infections from drug treatment centers, a prison and outpatient clinics and included blood donors as negative controls. Five drops of finger capillary blood were spotted on filter paper, and a venous blood sample was obtained. The samples were analyzed for HBsAg, anti-HBc, anti-HBs, anti-HCV, and anti-HIV levels as well as subjected to a combined nucleic acid test (NAT) for HBV DNA, HCV RNA and HIV RNA. RESULTS Samples from 404 subjects were screened (85 CHB, 116 CHC, 114 HIV and 99 blood donors). DBS had a sensitivity of > 96% and a specificity of > 98% for the detection of all three infections. NAT testing did not improve sensitivity, but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS (68% and 42%). CONCLUSION DBS sampling, combined with an automated analysis system, is a feasible screening method to diagnose chronic viral hepatitis and HIV infections outside of the health care system. PMID:27672281

  17. Molecular Characterization of the Human Immunodeficiency Virus Type 1 in Women and Their Vertically Infected Children

    PubMed Central

    Vaz, Sara Nunes; Giovanetti, Marta; Rego, Filipe Ferreira de Almeida; de Oliveira, Tulio; Danaviah, Siva; Gonçalves, Maria Luiza Freire; Alcantara, Luiz Carlos Junior

    2015-01-01

    Abstract Approximately 35 million people worldwide are infected with human immunodeficiency virus (HIV) around 3.2 million of whom are children under 15 years. Mother-to-child-transmission (MTCT) of HIV-1 accounts for 90% of all infections in children. Despite great advances in the prevention of MTCT in Brazil, children are still becoming infected. Samples from 19 HIV-1-infected families were collected. DNA was extracted and fragments from gag, pol, and env were amplified and sequenced directly. Phylogenetic reconstruction was performed. Drug resistance analyses were performed in pol and env sequences. We found 82.1% of subtype B and 17.9% of BF recombinants. A prevalence of 43.9% drug resistance-associated mutations in pol sequences was identified. Of the drug-naive children 33.3% presented at least one mutation related to protease inhibitor/nucleoside reverse transcriptase inhibitor/nonnucleoside reverse transcriptase inhibitor (PI/NRTI/NNRTI) resistance. The prevalence of transmitted drug resistance mutations was 4.9%. On env we found a low prevalence of HR1 (4.9%) and HR2 (14.6%) mutations. PMID:26200738

  18. Pneumocystis Pneumonia in Human Immunodeficiency Virus-infected Adults and Adolescents: Current Concepts and Future Directions.

    PubMed

    Tasaka, Sadatomo

    2015-01-01

    Pneumocystis jirovecii pneumonia (PCP) is one of the most common opportunistic infections in human immunodeficiency virus-infected adults. Colonization of Pneumocystis is highly prevalent among the general population and could be associated with the transmission and development of PCP in immunocompromised individuals. Although the microscopic demonstration of the organisms in respiratory specimens is still the golden standard of its diagnosis, polymerase chain reaction has been shown to have a high sensitivity, detecting Pneumocystis DNA in induced sputum or oropharyngeal wash. Serum β-D-glucan is useful as an adjunctive tool for the diagnosis of PCP. High-resolution computed tomography, which typically shows diffuse ground-glass opacities, is informative for the evaluation of immunocompromised patients with suspected PCP and normal chest radiography. Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line agent for the treatment of mild to severe PCP, although it is often complicated with various side effects. Since TMP-SMX is widely used for the prophylaxis, the putative drug resistance is an emerging concern.

  19. Dual Simian Foamy Virus/Human Immunodeficiency Virus Type 1 Infections in Persons from Côte d’Ivoire

    PubMed Central

    Switzer, William M.; Tang, Shaohua; Zheng, HaoQiang; Shankar, Anupama; Sprinkle, Patrick S.; Sullivan, Vickie; Granade, Timothy C.; Heneine, Walid

    2016-01-01

    Zoonotic transmission of simian retroviruses in West-Central Africa occurring in primate hunters has resulted in pandemic spread of human immunodeficiency viruses (HIVs) and human T-lymphotropic viruses (HTLVs). While simian foamy virus (SFV) and simian T- lymphotropic virus (STLV)-like infection were reported in healthy persons exposed to nonhuman primates (NHPs) in West-Central Africa, less is known about the distribution of these viruses in Western Africa and in hospitalized populations. We serologically screened for SFV and STLV infection using 1,529 specimens collected between 1985 and 1997 from Côte d’Ivoire patients with high HIV prevalence. PCR amplification and analysis of SFV, STLV, and HIV/SIV sequences from PBMCs was used to investigate possible simian origin of infection. We confirmed SFV antibodies in three persons (0.2%), two of whom were HIV-1-infected. SFV polymerase (pol) and LTR sequences were detected in PBMC DNA available for one HIV-infected person. Phylogenetic comparisons with new SFV sequences from African guenons showed infection likely originated from a Chlorocebus sabaeus monkey endemic to Côte d’Ivoire. 4.6% of persons were HTLV seropositive and PCR testing of PBMCs from 15 HTLV seroreactive persons identified nine with HTLV-1 and one with HTLV-2 LTR sequences. Phylogenetic analysis showed that two persons had STLV-1-like infections, seven were HTLV-1, and one was an HTLV-2 infection. 310/858 (53%), 8/858 (0.93%), and 18/858 (2.1%) were HIV-1, HIV-2, and HIV-positive but undifferentiated by serology, respectively. No SIV sequences were found in persons with HIV-2 antibodies (n = 1) or with undifferentiated HIV results (n = 7). We document SFV, STLV-1-like, and dual SFV/HIV infection in Côte d’Ivoire expanding the geographic range for zoonotic simian retrovirus transmission to West Africa. These findings highlight the need to define the public health consequences of these infections. Studying dual HIV-1/SFV infections in

  20. Dual Simian Foamy Virus/Human Immunodeficiency Virus Type 1 Infections in Persons from Côte d'Ivoire.

    PubMed

    Switzer, William M; Tang, Shaohua; Zheng, HaoQiang; Shankar, Anupama; Sprinkle, Patrick S; Sullivan, Vickie; Granade, Timothy C; Heneine, Walid

    2016-01-01

    Zoonotic transmission of simian retroviruses in West-Central Africa occurring in primate hunters has resulted in pandemic spread of human immunodeficiency viruses (HIVs) and human T-lymphotropic viruses (HTLVs). While simian foamy virus (SFV) and simian T- lymphotropic virus (STLV)-like infection were reported in healthy persons exposed to nonhuman primates (NHPs) in West-Central Africa, less is known about the distribution of these viruses in Western Africa and in hospitalized populations. We serologically screened for SFV and STLV infection using 1,529 specimens collected between 1985 and 1997 from Côte d'Ivoire patients with high HIV prevalence. PCR amplification and analysis of SFV, STLV, and HIV/SIV sequences from PBMCs was used to investigate possible simian origin of infection. We confirmed SFV antibodies in three persons (0.2%), two of whom were HIV-1-infected. SFV polymerase (pol) and LTR sequences were detected in PBMC DNA available for one HIV-infected person. Phylogenetic comparisons with new SFV sequences from African guenons showed infection likely originated from a Chlorocebus sabaeus monkey endemic to Côte d'Ivoire. 4.6% of persons were HTLV seropositive and PCR testing of PBMCs from 15 HTLV seroreactive persons identified nine with HTLV-1 and one with HTLV-2 LTR sequences. Phylogenetic analysis showed that two persons had STLV-1-like infections, seven were HTLV-1, and one was an HTLV-2 infection. 310/858 (53%), 8/858 (0.93%), and 18/858 (2.1%) were HIV-1, HIV-2, and HIV-positive but undifferentiated by serology, respectively. No SIV sequences were found in persons with HIV-2 antibodies (n = 1) or with undifferentiated HIV results (n = 7). We document SFV, STLV-1-like, and dual SFV/HIV infection in Côte d'Ivoire expanding the geographic range for zoonotic simian retrovirus transmission to West Africa. These findings highlight the need to define the public health consequences of these infections. Studying dual HIV-1/SFV infections in

  1. Hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infections in alcoholics.

    PubMed

    Prakash, Om; Mason, Andrew; Luftig, Ronald B; Bautista, Abraham P

    2002-07-01

    Approximately 400,000 individuals in the United States are co-infected with hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) and it is likely that almost one in two of these subjects consumes alcohol. The majority of these patients suffer an accelerated course of liver disease as manifested by the onset of cirrhosis within 5 to 10 years of developing HCV infection, as well as an increased risk of developing hepatocellular carcinoma (HCC). It is thought that chronic alcohol abuse mediates liver damage as a result of increased production of free radicals and proinflammatory cytokines. In the setting of chronic HCV infection, alcohol ingestion has an additional effect of diminishing immune clearance and increasing viral burden to hasten the onset of cirrhosis and HCC. Likewise, chronic HCV and HIV-1 co-infection results in a net increase in HCV burden; higher prevalence rates of HCV transmission to sexual partners and offspring, as well as an accelerated progression to end stage liver disease as compared to individuals with HCV infection alone. Thus, the synergistic effects of alcohol abuse and HIV-1 greatly impact on the morbidity and mortality for patients with HCV coinfection. Ultimately, this cumulative disease process will require far more aggressive management with abstinence and counseling for alcohol abuse; highly active antiretroviral therapy (HAART) for HIV infection and combination anti-viral therapy for HCV infection to stem the rapid progression to end stage liver disease. PMID:12086918

  2. Hepatitis B virus coinfection in human immunodeficiency virus-infected patients: A review

    PubMed Central

    Sun, Hsin-Yun; Sheng, Wang-Huei; Tsai, Mao-Song; Lee, Kuan-Yeh; Chang, Sui-Yuan; Hung, Chien-Ching

    2014-01-01

    Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to the shared modes of transmission, coinfection with HBV and human immunodeficiency virus (HIV) is not uncommon. It is estimated that 10% of HIV-infected patients worldwide are coinfected with HBV. In areas where an HBV vaccination program is implemented, the HBV seroprevalence has declined significantly. In HIV/HBV-coinfected patients, HBV coinfection accelerates immunologic and clinical progression of HIV infection and increases the risk of hepatotoxicity when combination antiretroviral therapy (cART) is initiated, while HIV infection increases the risk of hepatitis events, cirrhosis, and end-stage liver disease related to chronic HBV infection. With the advances in antiviral therapy, concurrent, successful long-term suppression of HIV and HBV replication can be achieved in the cART era. To reduce the disease burden of HBV infection among HIV-infected patients, adoption of safe sex practices, avoidance of sharing needles and diluent, HBV vaccination and use of cART containing tenofovir disoproxil fumarate plus emtricitabine or lamivudine are the most effective approaches. However, due to HIV-related immunosuppression, using increased doses of HBV vaccine and novel approaches to HBV vaccination are needed to improve the immunogenicity of HBV vaccine among HIV-infected patients. PMID:25356024

  3. Prevalence of feline leukemia virus and antibodies to feline immunodeficiency virus in cats in Norway.

    PubMed

    Ueland, K; Lutz, H

    1992-02-01

    Serum samples from 224 Norwegian cats were analyzed for the presence of feline leukemia virus (FeLV) p27 common core antigen, and for antibodies to feline immunodeficiency virus (FIV). Ninety specimens originated from the serum bank at the central referral clinic at the Norwegian College of Veterinary Medicine, which had been collected during the years 1983-1989; 67 sera were submitted from veterinarian practitioners; while 67 sera originated from cats presented for euthanasia. The cats were classified into one "healthy" and one "sick" group. Only 2.2% of sick cats and 1.2% of healthy cats showed FeLV antigenemia, a finding which is lower than which has been reported from many other countries. The prevalence of FIV antibodies was 10.1% in sick cats and 5.9% in healthy cats. Antibodies to FIV was most prevalent in male cats (14.7%) than in female cats (2.1%), and more prevalent among domestic cats (12.0%) compared to pedigree cats (2.4%). Antibodies to FIV in the cats demonstrated increasing prevalence with increasing age. It may be concluded that FeLV causes minor problems in Norwegian cats, while FIV is present in a similar prevalence to what is reported from other countries. PMID:1316024

  4. Insights into human immunodeficiency virus-hepatitis B virus co-infection in India

    PubMed Central

    Chakravarty, Runu; Pal, Ananya

    2015-01-01

    Shared routes of transmission lead to frequent human immunodeficiency virus (HIV)-hepatitis B virus (HBV) co-infection in a host which results in about 10% of HIV positive individuals to have chronic hepatitis B infection worldwide. In post-antiretroviral therapy era, liver diseases have emerged as the leading cause of morbidity and mortality in HIV-infected individuals and HBV co-infection have become the major health issue among this population particularly from the regions with endemic HBV infection. In setting of HIV-HBV co-infection, HIV significantly impacts the natural history of HBV infection, its disease profile and the treatment outcome in negative manner. Moreover, the epidemiological pattern of HBV infection and the diversity in HBV genome (genotypic and phenotypic) are also varied in HIV co-infected subjects as compared to HBV mono-infected individuals. Several reports on the abovementioned issues are available from developed parts of the world as well as from sub-Saharan African countries. In contrast, most of these research areas remained unexplored in India despite having considerable burden of HIV and HBV infections. This review discusses present knowledge from the studies on HIV-HBV co-infection in India and relevant reports from different parts of the world. Issues needed for the future research relevant to HIV-HBV co-infection in India are also highlighted here, including a call for further investigations on this field of study. PMID:26279986

  5. Liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfection: Diagnostic methods and clinical impact

    PubMed Central

    Sagnelli, Caterina; Martini, Salvatore; Pisaturo, Mariantonietta; Pasquale, Giuseppe; Macera, Margherita; Zampino, Rosa; Coppola, Nicola; Sagnelli, Evangelista

    2015-01-01

    Several non-invasive surrogate methods have recently challenged the main role of liver biopsy in assessing liver fibrosis in hepatitis C virus (HCV)-monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients, applied to avoid the well-known side effects of liver puncture. Serological tests involve the determination of biochemical markers of synthesis or degradation of fibrosis, tests not readily available in clinical practice, or combinations of routine tests used in chronic hepatitis and HIV/HCV coinfection. Several radiologic techniques have also been proposed, some of which commonly used in clinical practice. The studies performed to compare the prognostic value of non-invasive surrogate methods with that of the degree of liver fibrosis assessed on liver tissue have not as yet provided conclusive results. Each surrogate technique has shown some limitations, including the risk of over- or under-estimating the extent of liver fibrosis. The current knowledge on liver fibrosis in HIV/HCV-coinfected patients will be summarized in this review article, which is addressed in particular to physicians involved in this setting in their clinical practice. PMID:26523204

  6. Reactivation of Epstein-Barr virus during early infection with human immunodeficiency virus.

    PubMed Central

    Rahman, M A; Kingsley, L A; Atchison, R W; Belle, S; Breinig, M C; Ho, M; Rinaldo, C R

    1991-01-01

    Reactivation of Epstein-Barr virus (EBV) in early human immunodeficiency virus (HIV) infection was investigated in 49 homosexual men who seroconverted to HIV (cases) as compared with 49 matched controls who remained seronegative to HIV during a longitudinal study. EBV infection was reactivated in cases 6 months, but not 12 months, prior to HIV seroconversion as compared with controls and remained reactivated during 18 months of follow-up after HIV seroconversion, as shown by increases in immunoglobulin (Ig) G antibody titers to EBV early antigen. Antibody titers to EBV viral capsid antigen did not differ between cases and controls prior to the time of seroconversion to HIV but were significantly increased among cases by the first seropositive study visit and remained elevated during the 18 months after HIV seroconversion. Total serum IgG levels were increased in cases at the visit of seroconversion, and during 18 months of follow-up, but did not correlate with enhanced IgG production specific for EBV antigens. Significant decreases in numbers of CD4+ cells and increases in numbers of CD8+ cells during this early phase of HIV infection were not associated with changes in patterns of EBV antibody responses. Reactivation of EBV beginning 6 months before HIV seroconversion may have implications regarding the role of this herpesvirus in the pathogenesis of HIV. PMID:1650790

  7. Herpes simplex virus type 1 encephalitis in acquired immunodeficiency syndrome.

    PubMed

    Chrétien, F; Bélec, L; Hilton, D A; Flament-Saillour, M; Guillon, F; Wingertsmann, L; Baudrimont, M; de Truchis, P; Keohane, C; Vital, C; Love, S; Gray, F

    1996-10-01

    Herpes simplex (HSV) infection of the central nervous system is uncommon in AIDS and usually has an atypical topography. This review is centred around the case of a 49-year-old homosexual patient with AIDS who died from diffuse encephalopathy. Neuropathological examination revealed necrotic and haemorrhagic changes involving both temporal lobes, insulae and cingulate gyri. Cowdry type A intranuclear inclusion bodies were abundant but inflammation was minimal. Electron microscopy confirmed characteristic herpes virus particles. Immunocyto-chemistry was positive for HSV type 1 and 2. In situ hybridization and PCR, however, were positive for HSV type 1 but excluded HSV type 2. There was associated cytomegalovirus ventriculitis but clearly separated from HSV encephalitis. There were no histological features of HIV encephalitis and HIV could not be demonstrated by immunocytochemistry or by PCR to demonstrate proviral DNA. Apoptotic neurons were numerous in areas with a severe macrophage reaction. Only two pathological cases with characteristic limbic distribution and necrotic haemorrhagic histologic have been reported previously. The rarity of these reports suggests that in advanced AIDS, the immune reaction causing a typical necrotizing encephalitis cannot be mounted. Distinction between HSV type 1 and 2 infection may be difficult by immunocytochemistry and usually requires in situ hybridization, tissue culture or PCR. In AIDS patients, HSV-1 has been identified as responsible for encephalitis whereas HSV-2 has been more responsible for myelitis. Associated productive HIV infection of the CNS was found in none of the cases. In contrast, cytomegalovirus encephalitis was found in nine of 11 cases of AIDS-associated HSV encephalitis. PMID:8930949

  8. International military human immunodeficiency virus/acquired immunodeficiency syndrome policies and programs: strengths and limitations in current practice.

    PubMed

    Yeager, R; Hendrix, C W; Kingma, S

    2000-02-01

    A survey was conducted to evaluate military human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) policies and programs in 119 countries. Ninety-eight percent of the 62 respondents provide prevention education, 95% in group settings but only 53% individually. Predeployment briefings are more common than postdeployment briefings. Condoms are promoted more often than provided. Seventy-eight respondents report some form of mandatory HIV testing, and 58% perform mandatory recruit testing, with recruitment denied to HIV-positive individuals in 17%. Counseling accompanies mandatory testing less than voluntary testing. In-service care for AIDS patients is universal. Many military prevention programs can be improved through postdeployment briefings and proactive interventions involving education, condom distribution, and counseling combined with testing. Mandatory testing is often inconsistent with stated goals, and AIDS care policies may strain military budgets. Testing based on cost-benefit assessments may increase efficiency in military HIV control. Military budgets may benefit from greater civil-military cost sharing in AIDS care. PMID:10709366

  9. International military human immunodeficiency virus/acquired immunodeficiency syndrome policies and programs: strengths and limitations in current practice.

    PubMed

    Yeager, R; Hendrix, C W; Kingma, S

    2000-02-01

    A survey was conducted to evaluate military human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) policies and programs in 119 countries. Ninety-eight percent of the 62 respondents provide prevention education, 95% in group settings but only 53% individually. Predeployment briefings are more common than postdeployment briefings. Condoms are promoted more often than provided. Seventy-eight respondents report some form of mandatory HIV testing, and 58% perform mandatory recruit testing, with recruitment denied to HIV-positive individuals in 17%. Counseling accompanies mandatory testing less than voluntary testing. In-service care for AIDS patients is universal. Many military prevention programs can be improved through postdeployment briefings and proactive interventions involving education, condom distribution, and counseling combined with testing. Mandatory testing is often inconsistent with stated goals, and AIDS care policies may strain military budgets. Testing based on cost-benefit assessments may increase efficiency in military HIV control. Military budgets may benefit from greater civil-military cost sharing in AIDS care.

  10. New clinical and histological patterns of acute disseminated histoplasmosis in human immunodeficiency virus-positive patients with acquired immunodeficiency syndrome.

    PubMed

    Ollague Sierra, Jose E; Ollague Torres, Jose M

    2013-04-01

    Histoplasmosis has attained increasing relevance in the past 3 decades because of the appearance of the human immunodeficiency virus (HIV). In most immunocompetent persons, the infection is asymptomatic or can produce a respiratory condition with symptoms and radiological images similar to those observed in pulmonary tuberculosis; in non-HIV+ immunocompromised patients, it can cause respiratory symptoms or evolve into a disseminated infection. The same can occur in acquired immunodeficiency syndrome (AIDS) patients. We have observed a series of HIV+ patients with AIDS who presented with cutaneous histoplasmosis and in whom the clinical and histopathological features were highly unusual, including variable mucocutaneous lesions that were difficult to diagnose clinically. These patients displayed unusual, previously undescribed, histological patterns, including lichenoid pattern, nodular pseudomyxoid pattern, pyogenic granuloma-like pattern, perifollicular pattern, and superficial (S), mid (M), and deep perivascular dermatitis; and more commonly encountered patterns, such as histiocytic lobular panniculitis and focal nodular dermatitis. The novel histopathological patterns of cutaneous involvement by histoplasmosis seen in these patients resembled other common inflammatory and infectious conditions and required a high level of suspicion and the application of special stains for organisms for confirmation. These new, clinical, and histological findings do not seem to be commonly encountered in HIV- patients infected with the fungus but seem to be displayed most prominently in HIV+ patients with AIDS.

  11. Human immunodeficiency virus type 1 LTR TATA and TAR region sequences required for transcriptional regulation.

    PubMed

    Garcia, J A; Harrich, D; Soultanakis, E; Wu, F; Mitsuyasu, R; Gaynor, R B

    1989-03-01

    The human immunodeficiency virus (HIV) type 1 LTR is regulated at the transcriptional level by both cellular and viral proteins. Using HeLa cell extracts, multiple regions of the HIV LTR were found to serve as binding sites for cellular proteins. An untranslated region binding protein UBP-1 has been purified and fractions containing this protein bind to both the TAR and TATA regions. To investigate the role of cellular proteins binding to both the TATA and TAR regions and their potential interaction with other HIV DNA binding proteins, oligonucleotide-directed mutagenesis of both these regions was performed followed by DNase I footprinting and transient expression assays. In the TATA region, two direct repeats TC/AAGC/AT/AGCTGC surround the TATA sequence. Mutagenesis of both of these direct repeats or of the TATA sequence interrupted binding over the TATA region on the coding strand, but only a mutation of the TATA sequence affected in vivo assays for tat-activation. In addition to TAR serving as the site of binding of cellular proteins, RNA transcribed from TAR is capable of forming a stable stem-loop structure. To determine the relative importance of DNA binding proteins as compared to secondary structure, oligonucleotide-directed mutations in the TAR region were studied. Local mutations that disrupted either the stem or loop structure were defective in gene expression. However, compensatory mutations which restored base pairing in the stem resulted in complete tat-activation. This indicated a significant role for the stem-loop structure in HIV gene expression. To determine the role of TAR binding proteins, mutations were constructed which extensively changed the primary structure of the TAR region, yet left stem base pairing, stem energy and the loop sequence intact. These mutations resulted in decreased protein binding to TAR DNA and defects in tat-activation, and revealed factor binding specifically to the loop DNA sequence. Further mutagenesis which inverted

  12. Engineered vaginal lactobacillus strain for mucosal delivery of the human immunodeficiency virus inhibitor cyanovirin-N.

    PubMed

    Liu, Xiaowen; Lagenaur, Laurel A; Simpson, David A; Essenmacher, Kirsten P; Frazier-Parker, Courtney L; Liu, Yang; Tsai, Daniel; Rao, Srinivas S; Hamer, Dean H; Parks, Thomas P; Lee, Peter P; Xu, Qiang

    2006-10-01

    Women are at significant risk of human immunodeficiency virus (HIV) infection, with the cervicovaginal mucosa serving as a major portal for virus entry. Female-initiated preventatives, including topical microbicides, are urgently needed to help curtail the HIV/AIDS pandemic. Here we report on the development of a novel, live microbicide that employs a natural vaginal strain of Lactobacillus jensenii engineered to deliver the potent HIV inhibitor cyanovirin-N (CV-N). To facilitate efficient expression of CV-N by this bacterium, the L. jensenii 1153 genome was sequenced, allowing identification of native regulatory elements and sites for the chromosomal integration of heterologous genes. A CV-N expression cassette was optimized and shown to produce high levels of structurally intact CV-N when expressed in L. jensenii. Lactobacillus-derived CV-N was capable of inhibiting CCR5-tropic HIV(BaL) infectivity in vitro with a 50% inhibitory concentration of 0.3 nM. The CV-N expression cassette was stably integrated as a single copy into the bacterial chromosome and resolved from extraneous plasmid DNA without adversely affecting the bacterial phenotype. This bacterial strain was capable of colonizing the vagina and producing full-length CV-N when administered intravaginally to mice during estrus phase. The CV-N-producing Lactobacillus was genetically stable when propagated in vitro and in vivo. This work represents a major step towards the development of an inexpensive yet durable protein-based microbicide to block the heterosexual transmission of HIV in women. PMID:17005802

  13. An Orphan Seven-Transmembrane Domain Receptor Expressed Widely in the Brain Functions as a Coreceptor for Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus

    PubMed Central

    Edinger, Aimee L.; Hoffman, Trevor L.; Sharron, Matthew; Lee, Benhur; Yi, Yanji; Choe, Wonkyu; Kolson, Dennis L.; Mitrovic, Branka; Zhou, Yiqing; Faulds, Daryl; Collman, Ronald G.; Hesselgesser, Joseph; Horuk, Richard; Doms, Robert W.

    1998-01-01

    Both CD4 and an appropriate coreceptor are necessary for infection of cells by human immunodeficiency virus type 1 (HIV-1) and most strains of HIV-2. The chemokine receptors CCR5 and CXCR4 are the major HIV-1 coreceptors, although some virus strains can also utilize alternative coreceptors such as CCR3 to infect cells. In contrast, most if not all simian immunodeficiency virus (SIV) strains use CCR5 as a coreceptor, and many SIV strains can use CCR5 independently of CD4. In addition, several orphan seven-transmembrane receptors which can serve as HIV-1 and SIV coreceptors have been identified. Here we report that APJ, an orphan seven-transmembrane domain receptor with homology to the angiotensin receptor family, functions as a coreceptor for a number of HIV-1 and SIV strains. APJ was expressed widely in the human brain and in NT2N neurons. APJ transcripts were also detected by reverse transcription-PCR in the CD4-positive T-cell line C8166, but not in peripheral blood leukocytes, microglia, phytohemagglutinin (PHA)- or PHA/interleukin-2-stimulated peripheral blood mononuclear cells, monocytes, or monocyte-derived macrophages. The widespread distribution of APJ in the central nervous system coupled with its use as a coreceptor by some HIV-1 strains indicates that it may play a role in neuropathogenesis. PMID:9733831

  14. Infectious Simian/Human Immunodeficiency Virus with Human Immunodeficiency Virus Type 1 Subtype C from an African Isolate: Rhesus Macaque Model

    PubMed Central

    Ndung'u, Thumbi; Lu, Yichen; Renjifo, Boris; Touzjian, Neal; Kushner, Nicholas; Pena-Cruz, Victor; Novitsky, Vladimir A.; Lee, Tun-Hou; Essex, Max

    2001-01-01

    Human immunodeficiency virus type 1 (HIV-1) subtype C is responsible for more than 56% of all infections in the HIV and AIDS pandemic. It is the predominant subtype in the rapidly expanding epidemic in southern Africa. To develop a relevant model that would facilitate studies of transmission, pathogenesis, and vaccine development for this subtype, we generated SHIVMJ4, a simian/human immunodeficiency virus (SHIV) chimera based on HIV-1 subtype C. SHIVMJ4 contains the majority of env, the entire second exon of tat, and a partial sequence of the second exon of rev, all derived from a CCR5-tropic, primary isolate envelope clone from southern Africa. SHIVMJ4 replicated efficiently in human, rhesus, and pig-tailed macaque peripheral blood mononuclear cells (PBMCs) in vitro but not in CEMx174 cells. To assess in vivo infectivity, SHIVMJ4 was intravenously inoculated into four rhesus macaques (Macaca mulatta). All four animals became infected as determined through virus isolation, PCR analysis, and viral loads of 107 to 108 copies of viral RNA per ml of plasma during the primary infection phase. We have established a CCR5-tropic SHIVMJ4/rhesus macaque model that may be useful in the studies of HIV-1 subtype C immunology and biology and may also facilitate the evaluation of vaccines to control the spread of HIV-1 subtype C in southern Africa and elsewhere. PMID:11689623

  15. Construction and Use of a Replication-Competent Human Immunodeficiency Virus (HIV-1) that Expresses the Chloramphenicol Acetyltransferase Enzyme

    NASA Astrophysics Data System (ADS)

    Terwilliger, E. F.; Godin, B.; Sodroski, J. G.; Haseltine, W. A.

    1989-05-01

    The construction and properties of an infectious human immunodeficiency virus (HIV) that expresses the bacterial gene chloramphenicol acetyltransferase are described. This virus can be used in vitro to screen for drugs that inhibit HIV infection. The marked virus may also be used to trace the routes of infection from the site of inoculation in animal experiments.

  16. Human Immunodeficiency Virus/Hepatitis C Virus Coinfection in Spain: Prevalence and Patient Characteristics

    PubMed Central

    Berenguer, Juan; Rivero, Antonio; Jarrín, Inmaculada; Núñez, María J.; Vivancos, María J.; Crespo, Manel; Téllez, María J.; Domingo, Pere; Iribarren, José A.; Artero, Arturo; Márquez, Manuel; Santos, Ignacio; Moreno, Javier; Montero, Marta; González-García, Juan

    2016-01-01

    Background. The purpose of this study was to assess the prevalence of anti-hepatitis C virus (HCV) antibodies (Abs) and active HCV infection in human immunodeficiency virus (HIV)-infected (HIV+) patients in Spain in 2015. This was a cross-sectional study. Methods. The study was performed in 41 centers in 2015. Sample size was estimated for an accuracy of 2%, the number of patients from each hospital was determined by proportional allocation, and patients were selected using simple random sampling. Results. The reference population was 35 791 patients, and the sample size was 1867 patients. Hepatitis C virus serostatus was known in 1843 patients (98.7%). Hepatitis C virus-Abs were detected in 695 patients (37.7%), in whom the main route of HIV acquisition was injection drug use (75.4%). Of these 695 patients, 402 had HCV RNA, 170 had had a sustained viral response (SVR) after anti-HCV therapy, and 102 cleared HCV spontaneously. Hepatitis C virus-ribonucleic acid results were unknown in 21 cases. Genotype distribution (known in 367 patients) was 1a in 143 patients (39.0%), 4 in 90 (24.5%) patients, 1b in 69 (18.8%) patients, 3 in 57 (15.5%) patients, 2 in 5 (1.4%) patients, and mixed in 3 (0.8%) patients. Liver cirrhosis was present in 93 patients (23.1%) with active HCV infection and in 39 (22.9%) patients with SVR after anti-HCV therapy. Conclusions. The prevalence of HCV-Abs and active HCV infection in HIV+ patients in Spain is 37.7% and 22.1%, respectively; these figures are significantly lower than those recorded in 2002 and 2009. The predominant genotypes in patients with active HCV infection were 1a and 4. A high percentage of patients had cirrhosis. Cirrhosis is also common in patients with SVR after anti-HCV therapy. PMID:27186584

  17. Human Immunodeficiency Virus/Hepatitis C Virus Coinfection in Spain: Prevalence and Patient Characteristics.

    PubMed

    Berenguer, Juan; Rivero, Antonio; Jarrín, Inmaculada; Núñez, María J; Vivancos, María J; Crespo, Manel; Téllez, María J; Domingo, Pere; Iribarren, José A; Artero, Arturo; Márquez, Manuel; Santos, Ignacio; Moreno, Javier; Montero, Marta; González-García, Juan

    2016-03-01

    Background.  The purpose of this study was to assess the prevalence of anti-hepatitis C virus (HCV) antibodies (Abs) and active HCV infection in human immunodeficiency virus (HIV)-infected (HIV+) patients in Spain in 2015. This was a cross-sectional study. Methods.  The study was performed in 41 centers in 2015. Sample size was estimated for an accuracy of 2%, the number of patients from each hospital was determined by proportional allocation, and patients were selected using simple random sampling. Results.  The reference population was 35 791 patients, and the sample size was 1867 patients. Hepatitis C virus serostatus was known in 1843 patients (98.7%). Hepatitis C virus-Abs were detected in 695 patients (37.7%), in whom the main route of HIV acquisition was injection drug use (75.4%). Of these 695 patients, 402 had HCV RNA, 170 had had a sustained viral response (SVR) after anti-HCV therapy, and 102 cleared HCV spontaneously. Hepatitis C virus-ribonucleic acid results were unknown in 21 cases. Genotype distribution (known in 367 patients) was 1a in 143 patients (39.0%), 4 in 90 (24.5%) patients, 1b in 69 (18.8%) patients, 3 in 57 (15.5%) patients, 2 in 5 (1.4%) patients, and mixed in 3 (0.8%) patients. Liver cirrhosis was present in 93 patients (23.1%) with active HCV infection and in 39 (22.9%) patients with SVR after anti-HCV therapy. Conclusions.  The prevalence of HCV-Abs and active HCV infection in HIV+ patients in Spain is 37.7% and 22.1%, respectively; these figures are significantly lower than those recorded in 2002 and 2009. The predominant genotypes in patients with active HCV infection were 1a and 4. A high percentage of patients had cirrhosis. Cirrhosis is also common in patients with SVR after anti-HCV therapy. PMID:27186584

  18. Restricted replication of simian immunodeficiency virus strain 239 in macrophages is determined by env but is not due to restricted entry.

    PubMed Central

    Mori, K; Ringler, D J; Desrosiers, R C

    1993-01-01

    Virus derived from the infectious, pathogenic, molecular clone of simian immunodeficiency virus (SIV) called SIVmac239 replicates poorly in primary rhesus monkey alveolar macrophage cultures. Variants with three to nine amino acid changes in the envelope replicate 100 to 1,000 times more efficiently in these macrophage cultures than parental SIVmac239. Early events, including virus entry into cells, were analyzed by measuring the amounts of newly synthesized viral DNA 14 to 16 h after infection of macrophages by using a quantitative polymerase chain reaction method. SIVmac239 ws found to enter macrophages with an efficiency similar to that of the macrophage-tropic derivatives. The assay indeed measured newly synthesized viral DNA since detection was inhibited by the reverse transcriptase inhibitors azidothymidine and foscarnet and by heat inactivation of the virus stock prior to infection. Furthermore, entry of SIVmac239 and macrophage-tropic variant into macrophages was inhibited by monoclonal antibody against CD4. Analysis of the time course of viral DNA accumulation showed that although initial entry of SIVmac239 into cells occurred normally, subsequent logarithmic increases in the amounts of viral DNA associated with spread of virus through the macrophage cultures was blocked. Increasing the amount of SIVmac239 incubated with macrophages increased the amount of virus entering the cell, but this could not overcome the block to replication. Thus, restricted replication of SIVmac239 in macrophages is determined by the envelope, but surprisingly it is not due to restricted virus entry. Images PMID:7682627

  19. Resistance of human immunodeficiency virus type 1 to acyclic 6-phenylselenenyl- and 6-phenylthiopyrimidines.

    PubMed Central

    Nguyen, M H; Schinazi, R F; Shi, C; Goudgaon, N M; McKenna, P M; Mellors, J W

    1994-01-01

    Acyclic 6-phenylselenenyl- and 6-phenylthiopyrimidine derivatives are potent and specific inhibitors of human immunodeficiency virus type 1 (HIV-1). The development of in vitro resistance to two derivatives, 5-ethyl-1-(ethoxymethyl)-(6-phenylthio)-uracil (E-EPU), was evaluated by serial passage of HIV-1 in increasing concentrations of inhibitor. HIV-1 variants exhibiting > 500-fold resistance to E-EPSeU and E-EPU were isolated after sequential passage in 1, 5, and 10 microM inhibitor. The resistant variants exhibited coresistance to related acyclic 6-substituted pyrimidines and the HIV-1-specific inhibitors (+)-(5S)-4,5,6,7-tetrahydro-5- pyrimidines and the HIV-1-specific inhibitors (+)-(5S)-4,5,6,7-tetrahydro-5- methyl-6-(3-methyl-2-butenyl)imidazo[4,5,1-jk]benzodiazepin-2(1H)- thione (TIBO R82150) and nevirapine, but remained susceptible to 3'-azido-3'-deoxythymidine, 2',3'-dideoxycytidine, 2',3'-dideoxyinosine, and phosphonoformic acid. DNA sequence analysis of reverse transcriptase (RT) derived from E-EPSeU-resistant virus identified a Tyr (TAT)-to-Cys (TGT) mutation at either codon 188 (Cys-188; 9 of 15 clones) or codon 181 (Cys-181; 5 of 15 clones). The same amino acid changes were found in RT from E-EPU-resistant virus, but the Cys-181 mutation was more common (9 of 10 clones) than the Cys-188 mutation (1 of 10 clones). Site-specific mutagenesis and production of mutant recombinant viruses demonstrated that both the Cys-181 and Cys-188 mutations cause resistance to E-EPSeU and E-EPU. Of the two mutations, the Cys-188 substitution produced greater E-EPSeU and E-EPU resistance. The predominance of the Cys-188 mutation in E-EPSeU-resistant variants has not been noted for other classes of HIV-1 specific RT inhibitors. HIV-1 resistance is likely to limit the therapeutic efficacy of acyclic 6-substituted pyrimidines if they are used as monotherapy. PMID:7840579

  20. Viral resistance to human immunodeficiency virus type 1-specific pyridinone reverse transcriptase inhibitors.

    PubMed Central

    Nunberg, J H; Schleif, W A; Boots, E J; O'Brien, J A; Quintero, J C; Hoffman, J M; Emini, E A; Goldman, M E

    1991-01-01

    Human immunodeficiency virus type 1 (HIV-1)-specific pyridinone reverse transcriptase (RT) inhibitors prevent HIV-1 replication in cell culture (M. E. Goldman, J. H. Nunberg, J. A. O'Brien, J.C. Quintero, W. A. Schleif, K. F. Freund, S. L. Gaul, W. S. Saari, J. S. Wai, J. M. Hoffman, P. S. Anderson, D. J. Hupe, E. A. Emini, and A. M. Stern, Proc. Natl. Acad. Sci. USA 88:6863-6867, 1991). In contrast to nucleoside analog inhibitors, such as AZT, which need to be converted to triphosphates by host cells, these compounds act directly to inhibit RT via a mechanism which is noncompetitive with respect to deoxynucleoside triphosphates. As one approach to define the mechanism of action of pyridinone inhibitors, we isolated resistant mutants of HIV-1 in cell culture. Serial passage in the presence of inhibitor yielded virus which was 1,000-fold resistant to compounds of this class. Bacterially expressed RTs molecularly cloned from resistant viruses were also resistant. The resistant RT genes encoded two amino acid changes, K-103 to N and Y-181 to C, each of which contributed partial resistance. The mutation at amino acid 181 lies adjacent to the conserved YG/MDD motif found in most DNA and RNA polymerases. The mutation at amino acid 103 lies within a region of RT which may be involved in PPi binding. The resistant viruses, although sensitive to nucleoside analogs, were cross-resistant to the structurally unrelated RT inhibitors TIBO R82150 (R. Pauwels, K. Andries, J. Desmyter, D. Schols, M. J. Kukla, H. J. Breslin, A. Raeymaeckers, J. Van Gelder, R. Woestenborghs, J. Heykanti, K. Schellekens, M. A. C. Janssen, E. De Clercq, and P. A. J. Janssen, Nature [London] 343:470-474, 1990) and BI-RG-587 (V. J. Merluzzi, K. D. Hargrave, M. Labadia, K. Grozinger, M. Skoog, J. C. Wu, C.-K. Shih, K. Eckner, S. Hattox, J. Adams, A. S. Rosenthal, R. Faanes, R. J. Eckner, R. A. Koup, and J. L. Sullivan, Science 250:1411-1413, 1990). Thus, these nonnucleoside analog inhibitors may share a

  1. A molecularly cloned, pathogenic, neutralization-resistant simian immunodeficiency virus, SIVsmE543-3.

    PubMed Central

    Hirsch, V; Adger-Johnson, D; Campbell, B; Goldstein, S; Brown, C; Elkins, W R; Montefiori, D C

    1997-01-01

    An infectious molecular clone of simian immunodeficiency virus SIVsm was derived from a biological isolate obtained late in disease from an immunodeficient rhesus macaque (E543) with SIV-induced encephalitis. The molecularly cloned virus, SIVsmE543-3, replicated well in macaque peripheral blood mononuclear cells and monocyte-derived macrophages and resisted neutralization by heterologous sera which broadly neutralized genetically diverse SIV variants in vitro. SIVsmE543-3 was infectious and induced AIDS when inoculated intravenously into pig-tailed macaques (Macaca nemestrina). Two of four infected macaques developed no measurable SIV-specific antibody and succumbed to a wasting syndrome and SIV-induced meningoencephalitis by 14 and 33 weeks postinfection. The other two macaques developed antibodies reactive in Western blot and virus neutralization assays. One macaque was sacrificed at 1 year postinoculation, and the survivor has evidence of immunodeficiency, characterized by persistently low CD4 lymphocyte subsets in the peripheral blood. Plasma samples from these latter animals neutralized SIVsmE543-3 but with much lower efficiency than neutralization of other related SIV strains, confirming the difficulty by which this molecularly cloned virus is neutralized in vitro. SIVsmE543-3 will provide a valuable reagent for studying SIV-induced encephalitis, mapping determinants of neutralization, and determining the in vivo significance of resistance to neutralization in vitro. PMID:8995688

  2. Pregnancy and Human Herpesvirus 8 Reactivation in Human Immunodeficiency Virus Type 1-Infected Women▿

    PubMed Central

    Lisco, Andrea; Barbierato, Massimo; Fiore, Josè R.; Gasperini, Paola ; Favia, Anna; Volpe, Anna; Chironna, Maria; Pastore, Giuseppe; Chieco-Bianchi, Luigi; Calabrò, Maria Luisa

    2006-01-01

    To investigate the impact of pregnancy on human herpesvirus 8 (HHV-8) reactivation in human immunodeficiency virus type 1 (HIV-1)-infected women, the HHV-8 DNA presence and load were analyzed in peripheral blood mononuclear cells (PBMCs) and cervicovaginal secretions (CVSs) from 15 pregnant women coinfected with HIV-1 and HHV-8. HHV-8 detection was analyzed in relation to anti-HHV-8 antibodies and HIV-1-related parameters. Nucleotide sequence analysis of an ORFK1 hypervariable region of the HHV-8 strains was performed. HHV-8 was detected in maternal PBMCs (5/15 women) from the second trimester and in CVSs (5/15 women) mainly from the third trimester. The HHV-8 load significantly increased late in pregnancy in both maternal compartments and was associated with a significant increase in HIV-1 shedding in the genital tract. Antilytic antibodies were significantly more common in HHV-8 DNA-positive women. An elevated HHV-8 load was found in the PBMCs of an infant born to a mother with large amounts of HHV-8 in both compartments at delivery. Different ORFK1 subtypes were found in maternal samples, whereas the same subtype was identified in the mother-child pair. These data suggest that pregnancy may induce HHV-8 replication in HIV-1-infected women. An augmented HHV-8 load may, in turn, influence mother-to-child transmission, since one of the HIV-1-infected mothers with HHV-8 reactivation transmitted her ORFK1 subtype to the infant, who showed a high level of HHV-8 viremia indicative of a primary infection. This finding documents for the first time the perinatal transmission of a specific HHV-8 subtype. Vertical transmission may thus play a role in HHV-8 spread also in areas of subendemicity among HIV-1-infected women. PMID:16943357

  3. Establishment of latent herpes simplex virus type 1 infection in resistant, sensitive, and immunodeficient mouse strains.

    PubMed

    Ellison, A R; Yang, L; Voytek, C; Margolis, T P

    2000-03-01

    Productive infection with herpes simplex virus (HSV) type 1 is limited by both innate and adaptive immune mechanisms. The purpose of the current study was to determine whether these mechanisms also play a role in the establishment of latent HSV infection. First we examined the trigeminal ganglia (TG) of severe combined immunodeficiency (SCID), interferon-gamma knockout (GKO), and beige (a strain deficient in natural killer cell activity) mice following ocular inoculation with HSV. Although infection of SCID mice was invariably lethal, we consistently found latently infected neurons in the TG of these animals at 2-4 days postinoculation. HSV infection of GKO and beige mice, while not lethal, was characterized by a greater number of productively infected TG neurons and/or a delay in the time to peak productive infection compared to C57BL/6 controls. However, as assayed by both in situ hybridization for LAT expression and quantitative PCR (Q-PCR) for viral DNA, we found that HSV established a latent infection in GKO and beige mice as efficiently as in C57BL/6 controls. We subsequently examined the TG of "HSV-sensitive" strains of mice (Swiss-Webster, CBA, and BALB/c) following ocular infection with HSV. At the peak of acute ganglionic infection the number of productively infected TG neurons in each of these mouse strains was about sevenfold greater than in the "HSV-resistant" strain C57BL/6, consistent with previously reported differences in susceptibility to lethal challenge with HSV. However, as assayed by both in situ hybridization for LAT and Q-PCR for viral DNA, we found that HSV established a latent infection in Swiss-Webster, CBA, and BALB/c mice as efficiently as in C57BL/6 controls. We conclude that HSV efficiently establishes latent infection in the TG of mice in the absence of innate and adaptive immune mechanisms that are essential for limiting productive viral infection.

  4. Alpha interferon inhibits early stages of the human immunodeficiency virus type 1 replication cycle.

    PubMed Central

    Shirazi, Y; Pitha, P M

    1992-01-01

    In this study, we have analyzed the effect of human alpha interferon (IFN-alpha) on a single replication cycle of human immunodeficiency virus type 1 (HIV-1) infection in the lymphocytic cell line CEM-174, which is highly sensitive to the antiviral effects of IFN. Pretreatment of cells with 50 to 500 U of recombinant human IFN-alpha per ml resulted in a marked reduction in viral RNA and protein synthesis. The effect of IFN-alpha was dose dependent and was amplified in multiple infection cycles. IFN-induced inhibition of viral protein synthesis could be detected only when cells were treated with IFN-alpha prior to infection or when IFN-alpha was added up to 10 h postinfection, but not if IFN-alpha was added at the later stages of HIV-1 replication cycle or after the HIV-1 infection was already established. Analysis of the integrated HIV-1 provirus showed a marked decrease in the levels of proviral DNA in IFN-treated cells. Thus, in contrast to the previous studies on established HIV-1 infection in T cells, in which the IFN block appeared to be at the posttranslational level, during de novo infection, IFN-alpha interferes with an early step of HIV-1 replication cycle that occurs prior to the integration of the proviral DNA. These results indicate that the early IFN block of HIV-1 replication, which has been previously observed only in primary marcophages, can also be detected in the IFN-sensitive T cells, indicating that the early IFN block is not limited to macrophages. Images PMID:1738192

  5. Human papillomavirus detection from human immunodeficiency virus-infected Colombian women's paired urine and cervical samples.

    PubMed

    Munoz, Marina; Camargo, Milena; Soto-De Leon, Sara C; Sanchez, Ricardo; Parra, Diana; Pineda, Andrea C; Sussmann, Otto; Perez-Prados, Antonio; Patarroyo, Manuel E; Patarroyo, Manuel A

    2013-01-01

    Infection, coinfection and type-specific human papillomavirus (HPV) distribution was evaluated in human immunodeficiency virus (HIV)-positive women from paired cervical and urine samples. Paired cervical and urine samples (n = 204) were taken from HIV-positive women for identifying HPV-DNA presence by using polymerase chain reaction (PCR) with three generic primer sets (GP5+/6+, MY09/11 and pU1M/2R). HPV-positive samples were typed for six high-risk HPV (HR-HPV) (HPV-16, -18, -31, -33, -45 and -58) and two low-risk (LR-HPV) (HPV-6/11) types. Agreement between paired sample results and diagnostic performance was evaluated. HPV infection prevalence was 70.6% in cervical and 63.2% in urine samples. HPV-16 was the most prevalent HPV type in both types of sample (66.7% in cervical samples and 62.0% in urine) followed by HPV-31(47.2%) in cervical samples and HPV-58 (35.7%) in urine samples. There was 55.4% coinfection (infection by more than one type of HPV) in cervical samples and 40.2% in urine samples. Abnormal Papanicolau smears were observed in 25.3% of the women, presenting significant association with HPV-DNA being identified in urine samples. There was poor agreement of cervical and urine sample results in generic and type-specific detection of HPV. Urine samples provided the best diagnosis when taking cytological findings as reference. In conclusion including urine samples could be a good strategy for ensuring adherence to screening programs aimed at reducing the impact of cervical cancer, since this sample is easy to obtain and showed good diagnostic performance.

  6. Persistent Simian Immunodeficiency Virus Infection Drives Differentiation, Aberrant Accumulation, and Latent Infection of Germinal Center Follicular T Helper Cells

    PubMed Central

    Xu, Huanbin; Wang, Xiaolei; Malam, Naomi; Aye, Pyone P.; Alvarez, Xavier; Lackner, Andrew A.

    2015-01-01

    ABSTRACT CD4+ follicular T helper (Tfh) cells play a prominent role in humoral immune responses, but the mechanisms of their accumulation and infection in AIDS remain unclear. Here we found that germinal center (GC) Tfh cells, defined here as CXCR5+ PD-1HIGH CD4+ T cells, do not express the HIV coreceptor CCR5 yet serve as a latent reservoir in GCs. With disease progression, an expansion of GC Tfh cells is accompanied by increases in dysfunctional CD8+ T cells. In contrast, Tfh precursor (CXCR5− CD4+ T) cells in lymph nodes do express CCR5 and differentiate into GC Tfh cells following interleukin-6 (IL-6) and IL-21 stimulation, and viral DNA is detectable in fully differentiated GC Tfh cells ex vivo. This suggests that SIV-infected GC Tfh cells may be derived from Tfh precursor cell subsets that become infected in marginal zones and then migrate into GCs as fully mature GC Tfh cells that serve as persistent virus reservoirs. These findings suggest that viral persistence in lymph nodes drives compensatory differentiation, aberrant accumulation, and latent infection of GC Tfh cells, resulting in marked impairment of humoral immune responses. IMPORTANCE Generation of antibodies that can effectively eliminate viruses requires interactions of B cells with highly specialized T cells in GCs of lymphoid tissues called follicular T helper cells. Here we show that in simian immunodeficiency virus infection, these cells are initially infected in a precursor stage that leads to alterations in their homing, accumulation, and function that may be responsible for the inability of human immunodeficiency virus-infected patients to generate effective antibody responses. PMID:26608323

  7. A Vaccine against CCR5 Protects a Subset of Macaques upon Intravaginal Challenge with Simian Immunodeficiency Virus SIVmac251

    PubMed Central

    Hunter, Zoe; Jayashankar, Kartika; Peabody, Julianne; Montefiori, David; LaBranche, Celia C.; Keele, Brandon F.; Jensen, Kara; Abel, Kristina

    2014-01-01

    As an alternative to targeting human immunodeficiency virus (HIV), we have developed vaccines targeting CCR5, a self-protein critically involved in HIV replication and pathogenesis. By displaying peptides derived from CCR5 at high density on the surface of virus-like particles, we can efficiently induce high-titer IgG antibodies against this self-molecule. Here, we investigated whether prophylactic immunization of rhesus macaques with a particle-based vaccine targeting two regions of macaque CCR5 could prevent or suppress vaginal infection with highly virulent SIVmac251. Twelve macaques were vaccinated with a bacteriophage Qß-based vaccine targeting macaque CCR5 (Qß.CCR5). Six control animals were immunized with the Qß platform alone. All animals immunized with Qß.CCR5 developed high-titer anti-CCR5 antibody responses. Macaques were vaginally challenged with a high dose of SIVmac251. The mean peak viral RNA levels in the vaccinated groups were 30-fold lower than in the control group (106.8 versus 108.3 copies/ml plasma). Three of the 12 vaccinated macaques dramatically suppressed simian immunodeficiency virus (SIV) replication: peak viral loads were low (103 to 104 RNA copies/ml), and SIV RNA became undetectable from 6 weeks onward. No viral RNA or DNA could be detected in colon and lymph node biopsy specimens collected 13 months after challenge. In vivo depletion of CD8+ cells failed to induce a viral rebound. However, once anti-CCR5 antibody responses had waned, the 3 animals became infected after intravaginal and/or intravenous rechallenge. In conclusion, vaccination against CCR5 was associated with dramatic suppression of virus replication in a subset (25%) of macaques. These data support further research of vaccination against CCR5 to combat HIV infection. PMID:24307581

  8. Differentiation between human immunodeficiency virus type 1 (HIV-1) and HIV-2 isolates by nonradioisotopic reverse transcriptase-typing assay.

    PubMed Central

    Urabe, T; Sano, K; Nakano, T; Odawara, F; Lee, M H; Otake, T; Okubo, S; Hayami, M; Misaki, H; Baba, M

    1994-01-01

    We tested whether human immunodeficiency virus type 1 (HIV-1) could be differentiated from HIV-2 by a reverse transcriptase (RT)-typing assay that measured the reduction of enzyme activity owing to specific antibody. RT-inhibiting antibody was examined for HIV type specificity by a new nonradioisotopic RT assay. Antibodies from four rabbits immunized with recombinant HIV-1 RT and from 23 HIV-1-seropositive individuals all specifically inhibited the enzyme activities of two HIV-1 strains (LAV-1 and GH-3), three zidovudine-resistant HIV-1 mutants, and a recombinant HIV-1 RT. However, none of these antisera affected the activities of six HIV-2 strains (GH-1, GH-2, GH-4, GH-5, GH-6, LAV-2ROD), Rous-associated virus type 2, and DNA polymerase I from Escherichia coli. In contrast, HIV-2 antibody from a rabbit immunized with disrupted GH-1 virions blocked the enzyme activities of the six HIV-2 strains but not those of the three HIV-1 strains, Rous-associated virus type 2, or DNA polymerase I. These results indicate that the antigenic domains of HIV-1 and HIV-2 RTs recognized by their inhibiting antibodies are distinct from each other and are highly conserved. Clinical HIV isolates from 18 HIV-1-seropositive individuals and 3 HIV-2-seropositive Ghanaian individuals were identified as HIV-1 and HIV-2, respectively, by the nonradioisotopic RT-typing assay. Images PMID:7527425

  9. Simian immunodeficiency virus-specific CD8+ lymphocyte response in acutely infected rhesus monkeys.

    PubMed Central

    Yasutomi, Y; Reimann, K A; Lord, C I; Miller, M D; Letvin, N L

    1993-01-01

    To assess the possible role of cytotoxic T lymphocytes (CTLs) in containing the spread of human immunodeficiency virus in acutely infected individuals, the temporal evolution of the virus-specific CD8+ lymphocyte response was defined in simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys. A brief period of SIVmac plasma antigenemia was seen 9 to 16 days following intravenous infection with SIVmac, ending as the absolute number of CD8+ peripheral blood lymphocytes (PBLs) increased. In a prospective assessment of the ability of CD8+ lymphocytes of these monkeys to suppress SIVmac replication in autologous PBLs, inhibitory activity was detected as early as 4 days, with a more pronounced effect 12 to 16 days following infection. SIVmac Gag- and Nef-specific CD8+ effector cell activities were demonstrable in PBLs of animals by 2 weeks following virus inoculation. In fact, SIVmac-specific CTL precursors were documented in the PBLs of rhesus monkeys 4 to 6 days after SIVmac infection. These studies indicate that AIDS virus-specific CD8+ CTLs are present in PBLs within days of infection and may play an important role in containing the early spread of virus. PMID:8437240

  10. Primary Neuritic Hansen's Disease presenting as Ulnar Nerve Abscess in a Human Immunodeficiency Virus Positive Patient.

    PubMed

    Karjigi, S; Herakal, K; Murthy, S C; Bathina, A; Kusuma, M R; Nikhil, K R Y

    2015-01-01

    Leprosy has been increasingly known to have an enigmatic relationship with human immunodeficiency virus infection. Co-infection may result in atypical manifestations of leprosy. A 45-year old human immunodeficiency virus-positive male; agricultural laborer presented with a swelling over right elbow, right hand deformity, generalized itching and recurrent vesicles overthe perinasal area. Clinical and investigational findings were consistent with mononeuritic type of Hansen's disease with right sided silent ulnar nerve abscess, partial claw hand. CD4+ count of the patientwas 430 cells/cmm. This patient also hadherpes simplex labialis, with HIV-associated pruritus. To the best of our knowledge such an atypical presentation has not been reported earlier. PMID:26999990

  11. Prevalence of occult hepatitis C virus infection in the Iranian patients with human immunodeficiency virus infection.

    PubMed

    Bokharaei-Salim, Farah; Keyvani, Hossein; Esghaei, Maryam; Zare-Karizi, Shohreh; Dermenaki-Farahani, Sahar-Sadat; Hesami-Zadeh, Khashayar; Fakhim, Shahin

    2016-11-01

    Occult hepatitis C virus (HCV) infection is a new form of chronic HCV infection described by the presence of the genomic HCV-RNA in liver biopsy and/or peripheral blood mononuclear cell (PBMC) samples, and undetectable levels or absence of HCV-RNA and in the absence or presence of anti HCV antibodies in the plasma specimens. The aim of the present study was to evaluate the occurrence of occult HCV infection (OCI) among Iranian subjects infected with human immunodeficiency virus (HIV) using RT-nested PCR. From March 2014 until April 2015, 109 Iranian patients with established HIV infection were enrolled in this cross-sectional study. After extraction of viral RNA from the plasma and PBMC samples, HCV-RNA status was examined by RT-nested PCR using primers from the 5'-NTR. HCV genotyping was conducted using RFLP analysis. For the confirmation of HCV genotyping by RFLP method, the PCR products were sequenced. Of the 109 patients, 50 were positive for antibodies against HCV. The HCV-RNA was detected in PBMC specimens in 6 (10.2%) out of the total 59 patients negative for anti-HCV Abs and undetectable plasma HCV-RNA and also from 4 (8.0%) out of the total 50 patients positive for anti-HCV Abs and undetectable plasma HCV-RNA. HCV genotyping analysis showed that 6 (60.0%) patients were infected with HCV subtype 3a, 3 (30.0%) were infected with HCV subtype 1a and 1 (10.0%) patient was infected with HCV subtype 1b. This study revealed the incidence of OCI (9.2%) in HIV-infected Iranian patients. Hence, designing prospective studies focusing on the detection of OCI in these patients would provide more information. J. Med. Virol. 88:1960-1966, 2016. © 2016 Wiley Periodicals, Inc.

  12. Prevalence of occult hepatitis C virus infection in the Iranian patients with human immunodeficiency virus infection.

    PubMed

    Bokharaei-Salim, Farah; Keyvani, Hossein; Esghaei, Maryam; Zare-Karizi, Shohreh; Dermenaki-Farahani, Sahar-Sadat; Hesami-Zadeh, Khashayar; Fakhim, Shahin

    2016-11-01

    Occult hepatitis C virus (HCV) infection is a new form of chronic HCV infection described by the presence of the genomic HCV-RNA in liver biopsy and/or peripheral blood mononuclear cell (PBMC) samples, and undetectable levels or absence of HCV-RNA and in the absence or presence of anti HCV antibodies in the plasma specimens. The aim of the present study was to evaluate the occurrence of occult HCV infection (OCI) among Iranian subjects infected with human immunodeficiency virus (HIV) using RT-nested PCR. From March 2014 until April 2015, 109 Iranian patients with established HIV infection were enrolled in this cross-sectional study. After extraction of viral RNA from the plasma and PBMC samples, HCV-RNA status was examined by RT-nested PCR using primers from the 5'-NTR. HCV genotyping was conducted using RFLP analysis. For the confirmation of HCV genotyping by RFLP method, the PCR products were sequenced. Of the 109 patients, 50 were positive for antibodies against HCV. The HCV-RNA was detected in PBMC specimens in 6 (10.2%) out of the total 59 patients negative for anti-HCV Abs and undetectable plasma HCV-RNA and also from 4 (8.0%) out of the total 50 patients positive for anti-HCV Abs and undetectable plasma HCV-RNA. HCV genotyping analysis showed that 6 (60.0%) patients were infected with HCV subtype 3a, 3 (30.0%) were infected with HCV subtype 1a and 1 (10.0%) patient was infected with HCV subtype 1b. This study revealed the incidence of OCI (9.2%) in HIV-infected Iranian patients. Hence, designing prospective studies focusing on the detection of OCI in these patients would provide more information. J. Med. Virol. 88:1960-1966, 2016. © 2016 Wiley Periodicals, Inc. PMID:27463051

  13. Complete genome analysis of hepatitis B virus in human immunodeficiency virus infected and uninfected South Africans.

    PubMed

    Gededzha, Maemu P; Muzeze, Muxe; Burnett, Rosemary J; Amponsah-Dacosta, Edina; Mphahlele, M Jeffrey; Selabe, Selokela G

    2016-09-01

    Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections are highly endemic in South Africa. Data on the complete genome sequences of HBV in HIV-positive patients in South Africa are scanty. This study characterized the complete HBV genome isolated from both HIV-positive and negative patients at the Dr George Mukhari Academic Hospital (DGMAH), Pretoria. Serum samples from nine (five HIV-positive and four HIV-negative) patients attending the DGMAH from 2007 to 2011 were serologically tested, amplified, and sequenced for complete genome. Phylogenetic tree was constructed using MEGA6.0. Mutations were analyzed by comparing the sequences with genotype-matched GenBank references. Eight patients were HBsAg positive, with only one from the HIV positive group being negative. Phylogenetic analysis of the complete genome sequences classified them into five genotypes; A1 (n = 4), A2 (n = 1), C1 (n = 2), D1 (n = 1), and D3 (n = 1). Deletions up to 35 nucleotides in length were identified in this study. No drug resistance mutations were identified in the P ORF, while the L217R mutation was identified in one subgenotype A2 sequence. The double (A1762T/G1764A) and triple (T1753C/A1762T/G1764A) mutations in the Basal core promoter were identified in four and two sequences, respectively. In the core region, mutation G1888A was identified in four of the subgenotype A1 sequences. In conclusion, this study has added to the limited South African data on HBV genotypes and mutations in HBV/HIV co-infected and HBV mono-infected patients, based on complete HBV genome analysis. Subgenotype A1 was predominant, and no drug-resistant mutants were detected in the study. J. Med. Virol. 88:1560-1566, 2016. © 2016 Wiley Periodicals, Inc.

  14. Classification of hepatitis C virus and human immunodeficiency virus-1 sequences with the branching index.

    PubMed

    Hraber, Peter; Kuiken, Carla; Waugh, Mark; Geer, Shaun; Bruno, William J; Leitner, Thomas

    2008-09-01

    Classification of viral sequences should be fast, objective, accurate and reproducible. Most methods that classify sequences use either pair-wise distances or phylogenetic relations, but cannot discern when a sequence is unclassifiable. The branching index (BI) combines distance and phylogeny methods to compute a ratio that quantifies how closely a query sequence clusters with a subtype clade. In the hypothesis-testing framework of statistical inference, the BI is compared with a threshold to test whether sufficient evidence exists for the query sequence to be classified among known sequences. If above the threshold, the null hypothesis of no support for the subtype relation is rejected and the sequence is taken as belonging to the subtype clade with which it clusters on the tree. This study evaluates statistical properties of the BI for subtype classification in hepatitis C virus (HCV) and human immunodeficiency virus-1 (HIV-1). Pairs of BI values with known positive- and negative-test results were computed from 10,000 random fragments of reference alignments. Sampled fragments were of sufficient length to contain phylogenetic signals that grouped reference sequences together properly into subtype clades. For HCV, a threshold BI of 0.71 yields 95.1% agreement with reference subtypes, with equal false-positive and false-negative rates. For HIV-1, a threshold of 0.66 yields 93.5% agreement. Higher thresholds can be used where lower false-positive rates are required. In synthetic recombinants, regions without breakpoints are recognized accurately; regions with breakpoints do not represent any known subtype uniquely. Web-based services for viral subtype classification with the BI are available online.

  15. Twenty years of human immunodeficiency virus care at the Mayo Clinic: Past, present and future.

    PubMed

    Cummins, Nathan W; Badley, Andrew D; Kasten, Mary J; Sampath, Rahul; Temesgen, Zelalem; Whitaker, Jennifer A; Wilson, John W; Yao, Joseph D; Zeuli, John; Rizza, Stacey A

    2016-05-12

    The Mayo human immunodeficiency virus (HIV) Clinic has been providing patient centered care for persons living with HIV in Minnesota and beyond for the past 20 years. Through multidisciplinary engagement, vital clinical outcomes such as retention in care, initiation of antiretroviral therapy and virologic suppression are maximized. In this commentary, we describe the history of the Mayo HIV Clinic and its best practices, providing a "Mayo Model" of HIV care that exceeds national outcomes and may be applicable in other settings.

  16. Pre-exposure prophylaxis for human immunodeficiency virus: the past, present, and future.

    PubMed

    Castel, Amanda D; Magnus, Manya; Greenberg, Alan E

    2014-12-01

    This article presents an overview of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) prevention. The authors describe the past animal and human research that has been conducted that informs our current understanding of PrEP; summarize ongoing research in the area, including describing new regimens and delivery mechanisms being studied for PrEP; and highlight key issues that must be addressed in order to implement and optimize the use of this HIV prevention tool.

  17. Human Immunodeficiency Virus Type 1 Coat Protein Neurotoxicity Mediated by Nitric Oxide in Primary Cortical Cultures

    NASA Astrophysics Data System (ADS)

    Dawson, Valina L.; Dawson, Ted M.; Uhl, George R.; Snyder, Solomon H.

    1993-04-01

    The human immunodeficiency virus type 1 coat protein, gp120, kills neurons in primary cortical cultures at low picomolar concentrations. The toxicity requires external glutamate and calcium and is blocked by glutamate receptor antagonists. Nitric oxide (NO) contributes to gp120 toxicity, since nitroarginine, an inhibitor of NO synthase, prevents toxicity as does deletion of arginine from the incubation medium and hemoglobin, which binds NO. Superoxide dismutase also attenuates toxicity, implying a role for superoxide anions.

  18. Characterization of regionally associated feline immunodeficiency virus (FIV) in bobcats (Lynx rufus).

    PubMed

    Lagana, Danielle M; Lee, Justin S; Lewis, Jesse S; Bevins, Sarah N; Carver, Scott; Sweanor, Linda L; McBride, Roy; McBride, Caleb; Crooks, Kevin R; VandeWoude, Sue

    2013-07-01

    Feline immunodeficiency virus (FIV) classically infects felid species with highly divergent species-specific FIVs. However, recent studies have detected an FIV strain infecting both bobcats (Lynx rufus) and pumas (Puma concolor) in California and Florida. To further investigate this observation, we evaluated FIV from bobcats in Florida (n=25) and Colorado (n=80) between 2008 and 2011. Partial viral sequences from five Florida bobcats cluster with previously published sequences from Florida panthers. We did not detect FIV in Colorado bobcats.

  19. Human immunodeficiency virus testing for patient-based and population-based diagnosis.

    PubMed

    Albritton, W L; Vittinghoff, E; Padian, N S

    1996-10-01

    Laboratory testing for human immunodeficiency virus (HIV) has been introduced for individual patient-based diagnosis as well as high-risk and low-risk population-based screening. The choice of test, confirmatory algorithm, and interpretative criteria used depend on the clinical setting. In the context of general population-based testing, factors affecting test performance will have to be considered carefully in the development of testing policy. PMID:8843247

  20. A fusion inhibitor prevents spread of immunodeficiency viruses, but not activation of virus-specific T cells, by dendritic cells.

    PubMed

    Frank, I; Stössel, H; Gettie, A; Turville, S G; Bess, J W; Lifson, J D; Sivin, I; Romani, N; Robbiani, M

    2008-06-01

    Dendritic cells (DCs) play a key role in innate immune responses, and their interactions with T cells are critical for the induction of adaptive immunity. However, immunodeficiency viruses are efficiently captured by DCs and can be transmitted to and amplified in CD4(+) T cells, with potentially deleterious effects on the induction of immune responses. In DC-T-cell cocultures, contact with CD4(+), not CD8(+), T cells preferentially facilitated virus movement to and release at immature and mature DC-T-cell contact sites. This occurred within 5 min of DC-T-cell contact. While the fusion inhibitor T-1249 did not prevent virus capture by DCs or the release of viruses at the DC-T-cell contact points, it readily blocked virus transfer to and amplification in CD4(+) T cells. Higher doses of T-1249 were needed to block the more robust replication driven by mature DCs. Virus accumulated in DCs within T-1249-treated cocultures but these DCs were actually less infectious than DCs isolated from untreated cocultures. Importantly, T-1249 did not interfere with the stimulation of virus-specific CD4(+) and CD8(+) T-cell responses when present during virus-loading of DCs or for the time of the DC-T-cell coculture. These results provide clues to identifying strategies to prevent DC-driven virus amplification in CD4(+) T cells while maintaining virus-specific immunity, an objective critical in the development of microbicides and therapeutic vaccines.

  1. Broadly Neutralizing Human Immunodeficiency Virus Type 1 Antibody Gene Transfer Protects Nonhuman Primates from Mucosal Simian-Human Immunodeficiency Virus Infection

    PubMed Central

    Saunders, Kevin O.; Wang, Lingshu; Joyce, M. Gordon; Yang, Zhi-Yong; Balazs, Alejandro B.; Cheng, Cheng; Ko, Sung-Youl; Kong, Wing-Pui; Rudicell, Rebecca S.; Georgiev, Ivelin S.; Duan, Lijie; Foulds, Kathryn E.; Donaldson, Mitzi; Xu, Ling; Schmidt, Stephen D.; Todd, John-Paul; Baltimore, David; Roederer, Mario; Haase, Ashley T.; Kwong, Peter D.; Rao, Srinivas S.

    2015-01-01

    ABSTRACT Broadly neutralizing antibodies (bnAbs) can prevent lentiviral infection in nonhuman primates and may slow the spread of human immunodeficiency virus type 1 (HIV-1). Although protection by passive transfer of human bnAbs has been demonstrated in monkeys, durable expression is essential for its broader use in humans. Gene-based expression of bnAbs provides a potential solution to this problem, although immune responses to the viral vector or to the antibody may limit its durability and efficacy. Here, we delivered an adeno-associated viral vector encoding a simianized form of a CD4bs bnAb, VRC07, and evaluated its immunogenicity and protective efficacy. The expressed antibody circulated in macaques for 16 weeks at levels up to 66 μg/ml, although immune suppression with cyclosporine (CsA) was needed to sustain expression. Gene-delivered simian VRC07 protected against simian-human immunodeficiency virus (SHIV) infection in monkeys 5.5 weeks after treatment. Gene transfer of an anti-HIV antibody can therefore protect against infection by viruses that cause AIDS in primates when the host immune responses are controlled. IMPORTANCE Sustained interventions that can prevent HIV-1 infection are needed to halt the spread of the HIV-1 pandemic. The protective capacity of anti-HIV antibody gene therapy has been established in mouse models of HIV-1 infection but has not been established for primates. We show here a proof-of-concept that gene transfer of anti-HIV antibody genes can protect against infection by viruses that cause AIDS in primates when host immune responses are controlled. PMID:26041300

  2. Seroprevalence and genomic divergence of circulating strains of feline immunodeficiency virus among Felidae and Hyaenidae species.

    PubMed

    Troyer, Jennifer L; Pecon-Slattery, Jill; Roelke, Melody E; Johnson, Warren; VandeWoude, Sue; Vazquez-Salat, Nuria; Brown, Meredith; Frank, Laurence; Woodroffe, Rosie; Winterbach, Christiaan; Winterbach, Hanlie; Hemson, Graham; Bush, Mitch; Alexander, Kathleen A; Revilla, Eloy; O'Brien, Stephen J

    2005-07-01

    Feline immunodeficiency virus (FIV) infects numerous wild and domestic feline species and is closely related to human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Species-specific strains of FIV have been described for domestic cat (Felis catus), puma (Puma concolor), lion (Panthera leo), leopard (Panthera pardus), and Pallas' cat (Otocolobus manul). Here, we employ a three-antigen Western blot screening (domestic cat, puma, and lion FIV antigens) and PCR analysis to survey worldwide prevalence, distribution, and genomic differentiation of FIV based on 3,055 specimens from 35 Felidae and 3 Hyaenidae species. Although FIV infects a wide variety of host species, it is confirmed to be endemic in free-ranging populations of nine Felidae and one Hyaenidae species. These include the large African carnivores (lion, leopard, cheetah, and spotted hyena), where FIV is widely distributed in multiple populations; most of the South American felids (puma, jaguar, ocelot, margay, Geoffroy's cat, and tigrina), which maintain a lower FIV-positive level throughout their range; and two Asian species, the Pallas' cat, which has a species-specific strain of FIV, and the leopard cat, which has a domestic cat FIV strain in one population. Phylogenetic analysis of FIV proviral sequence demonstrates that most species for which FIV is endemic harbor monophyletic, genetically distinct species-specific FIV strains, suggesting that FIV transfer between cat species has occurred in the past but is quite infrequent today.

  3. Seroprevalence and Genomic Divergence of Circulating Strains of Feline Immunodeficiency Virus among Felidae and Hyaenidae Species†

    PubMed Central

    Troyer, Jennifer L.; Pecon-Slattery, Jill; Roelke, Melody E.; Johnson, Warren; VandeWoude, Sue; Vazquez-Salat, Nuria; Brown, Meredith; Frank, Laurence; Woodroffe, Rosie; Winterbach, Christiaan; Winterbach, Hanlie; Hemson, Graham; Bush, Mitch; Alexander, Kathleen A.; Revilla, Eloy; O'Brien, Stephen J.

    2005-01-01

    Feline immunodeficiency virus (FIV) infects numerous wild and domestic feline species and is closely related to human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Species-specific strains of FIV have been described for domestic cat (Felis catus), puma (Puma concolor), lion (Panthera leo), leopard (Panthera pardus), and Pallas' cat (Otocolobus manul). Here, we employ a three-antigen Western blot screening (domestic cat, puma, and lion FIV antigens) and PCR analysis to survey worldwide prevalence, distribution, and genomic differentiation of FIV based on 3,055 specimens from 35 Felidae and 3 Hyaenidae species. Although FIV infects a wide variety of host species, it is confirmed to be endemic in free-ranging populations of nine Felidae and one Hyaenidae species. These include the large African carnivores (lion, leopard, cheetah, and spotted hyena), where FIV is widely distributed in multiple populations; most of the South American felids (puma, jaguar, ocelot, margay, Geoffroy's cat, and tigrina), which maintain a lower FIV-positive level throughout their range; and two Asian species, the Pallas' cat, which has a species-specific strain of FIV, and the leopard cat, which has a domestic cat FIV strain in one population. Phylogenetic analysis of FIV proviral sequence demonstrates that most species for which FIV is endemic harbor monophyletic, genetically distinct species-specific FIV strains, suggesting that FIV transfer between cat species has occurred in the past but is quite infrequent today. PMID:15956574

  4. Cocaine-mediated enhancement of virus replication in macrophages: implications for human immunodeficiency virus-associated dementia.

    PubMed

    Dhillon, Navneet K; Williams, Rachel; Peng, Fuwang; Tsai, Yi-Jou; Dhillon, Sukhbir; Nicolay, Brandon; Gadgil, Milind; Kumar, Anil; Buch, Shilpa J

    2007-12-01

    Injection drug use has been recognized as a major risk factor for acquired immunodeficiency syndrome (AIDS) from the outset of the epidemic. Cocaine, one of the most widely abused drugs in the United States, can both impair the functions of macrophages and CD4(+) lymphocytes and also activate human immunodeficiency virus (HIV)-1 expression in these cells. Because the brain is the target organ for both cocaine and HIV, the objective of the present study was to explore the effects of cocaine on virus replication in macrophages, the target cells for the virus in the central nervous system (CNS). Cocaine markedly enhanced virus production in simian human immunodeficiency virus (SHIV)-infected monocyte-derived macrophages (MDMs) and in U1 cells, a chronically infected promonocytic cell line as monitored by enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry. Cocaine treatment also resulted in the activation of nuclear factor (NF)-kappa B and transcriptional activation of the HIV-LTR (long terminal repeat) gag-GFP (green fluorescent protein). Analyses of chemokines in cocaine-treated macrophages by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Luminex assays suggested increased expression of interleukin (IL)-10, a cytokine that is known to promote HIV replication in MDMs. In addition to enhancing IL-10 expression, cocaine also caused an up-regulation of the macrophage activation marker, human leukocyte antigen (HLA)-DR, in MDMs. The synergistic effect of cocaine on virus replication and its enhancement of host activation markers suggest that cocaine functions at multiple pathways to accelerate HIV-associated dementia (HAD). PMID:18097880

  5. [Oral plasmablastic lymphoma in a human immunodeficiency virus positive child: a case report].

    PubMed

    Astolfo, María Florencia; D'Antonio, Federico; Dartiguelongue, Juan B; Arabolaza, María N; Cheistwer, Ariel; De Matteo, Elena; Torrado, Lidia; Martínez Iriart, Emilio

    2016-04-01

    Plasmablastic lymphoma is a rare and aggressive subtype of diffuse large B cell non-Hodgkin lymphoma, originally described in the oral cavity of male adults with acquired immune deficiency syndrome. It is composed of neoplastic ceils which resemble immunoblasts but present immunophenotype distinctive of plasma cell and Epstein-Barr virus latent infection. In children, it is an even rarer disease. We present a case of oral plasmablastic lymphoma in a vertically transmitted human immunodeficiency virus-positive five-year-old child.

  6. Peptidomimetic therapeutic agents targeting the protease enzyme of the human immunodeficiency virus and hepatitis C virus.

    PubMed

    Tsantrizos, Youla S

    2008-10-01

    During the past two decades, great strides have been made in the design of peptidomimetic drugs for the treatment of viral infections, despite the stigma of poor drug-like properties, low oral absorption, and high clearance associated with such compounds. This Account summarizes the progress made toward overcoming such liabilities and highlights the drug discovery efforts that have focused specifically on human immunodeficiency virus (HIV) and hepatitis C virus (HCV) protease inhibitors. The arsenal against the incurable disease AIDS, which is caused by HIV infection, includes peptidomimetic compounds that target the virally encoded aspartic protease enzyme. This enzyme is essential to the production of mature HIV particles and plays a key role in maintaining infectivity. However, because of the rapid genomic evolution of viruses, an inevitable consequence in the treatment of all viral infections is the emergence of resistance to the drugs. Therefore, the incomplete suppression of HIV in treatment-experienced AIDS patients will continue to drive the search for more effective therapeutic agents that exhibit efficacy against the mutants raised by the earlier generation of protease inhibitors. Currently, a number of substrate-based peptidomimetic agents that target the virally encoded HCV NS3/4A protease are in clinical development. Mechanistically, these inhibitors can be generally divided into activated carbonyls that are transition-state mimics or compounds that tap into the feedback mode of enzyme-product inhibition. In the HCV field, there is justified optimism that a number of these compounds will soon reach commercialization as therapeutic agents for the treatment of HCV infections. Structural research has guided the successful design of both HIV and HCV protease inhibitors. X-ray crystallography, NMR, and computational studies have provided valuable insight in to the free-state preorganization of peptidomimetic ligands and their enzyme-bound conformation

  7. Plasma viral RNA load predicts disease progression in accelerated feline immunodeficiency virus infection.

    PubMed Central

    Diehl, L J; Mathiason-Dubard, C K; O'Neil, L L; Hoover, E A

    1996-01-01

    Viral RNA load has been shown to indicate disease stage and predict the rapidity of disease progression in human immunodeficiency virus type 1 (HIV-1)-infected individuals. We had previously demonstrated that feline immunodeficiency virus (FIV) RNA levels in plasma correlate with disease stage in infected cats. Here we expand upon those observations by demonstrating that plasma virus load is 1 to 2 logs higher in cats with rapidly progressive FIV disease than in long-term survivors. Differences in plasma FIV RNA levels are evident by 1 to 2 weeks after infection and are consistent throughout infection. We also evaluated humoral immune responses in FIV-infected cats for correlation with survival times. Total anti-FIV antibody titers did not differ between cats with rapidly progressive FIV disease and long-term survivors. These findings indicate that virus replication plays an important role in FIV disease progression, as it does in HIV-1 disease progression. The parallels in virus loads and disease progressions between HIV-1 and FIV support the idea that the accelerated disease model is well suited for the study of therapeutic agents directed at reducing lentiviral replication. PMID:8642679

  8. Cell cycle regulation of human immunodeficiency virus type 1 integration in T cells: antagonistic effects of nuclear envelope breakdown and chromatin condensation

    SciTech Connect

    Mannioui, Abdelkrim . E-mail: karim.mannioui@chu-stlouis.fr; Schiffer, Cecile . E-mail: cecile.schiffer@voila.fr; Felix, Nathalie . E-mail: nathalie.felix@chu-stlouis.fr

    2004-11-10

    We examined the influence of mitosis on the kinetics of human immunodeficiency virus type 1 integration in T cells. Single-round infection of cells arrested in G1b or allowed to synchronously proceed through division showed that mitosis delays virus integration until 18-24 h postinfection, whereas integration reaches maximum levels by 15 h in G1b-arrested cells. Subcellular fractionation of metaphase-arrested cells indicated that, while nuclear envelope disassembly facilitates docking of viral DNA to chromatin, chromosome condensation directly antagonizes and therefore delays integration. As a result of the balance between the two effects, virus integration efficiency is eventually up to threefold greater in dividing cells. At the single-cell level, using a green fluorescent protein-expressing reporter virus, we found that passage through mitosis leads to prominent asymmetric segregation of the viral genome in daughter cells without interfering with provirus expression.

  9. A Pilot Study of Raltegravir Plus Combination Antiretroviral Therapy in Early Human Immunodeficiency Virus Infection: Challenges and Lessons Learned.

    PubMed

    Collier, Ann C; Chun, Tae-Wook; Maenza, Janine; Coombs, Robert W; Tapia, Kenneth; Chang, Ming; Stevens, Claire E; Justement, J Shawn; Murray, Danielle; Stekler, Joanne D; Mullins, James I; Holte, Sarah E

    2016-01-01

    Availability of integrase strand transfer inhibitors created interest in determining whether their use would decrease persistently infected cell numbers. This study hypothesized that adding raltegravir (RAL) to standard antiretroviral therapy (ART) would decrease human immunodeficiency virus (HIV)-infected CD4(+) T cells more than standard combination ART. This was a pilot, randomized study comparing open-label standard triple ART to standard triple ART plus RAL over 96 weeks in ART-naive adults with early HIV infection. The primary objective was to compare quantity and trajectory of HIV DNA. Eighty-two persons were referred. A diverse set of reasons precluded the enrollment of all but 10. Those who enrolled and completed the study had an estimated median duration of HIV infection of 74 days at ART start. The groups had similar baseline characteristics. The RAL group had more rapid first phase plasma HIV RNA decay (0.67 log10 copies/mL/day) than with combination ART (0.34 log10copies/mL/day), p = 0.037. Second phase HIV RNA decay, residual viremia, cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circle levels did not differ between groups. Among those with entry plasma HIV RNA levels above the median, 2LTR circles were significantly lower over time than in those with lower entry HIV RNA levels (p = 0.02). Our results suggest homogeneity of responses in cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circles with early HIV in both ART groups. The kinetics of 2LTR DNA did not reflect the kinetics of plasma HIV RNA decline following ART initiation.

  10. A Pilot Study of Raltegravir Plus Combination Antiretroviral Therapy in Early Human Immunodeficiency Virus Infection: Challenges and Lessons Learned.

    PubMed

    Collier, Ann C; Chun, Tae-Wook; Maenza, Janine; Coombs, Robert W; Tapia, Kenneth; Chang, Ming; Stevens, Claire E; Justement, J Shawn; Murray, Danielle; Stekler, Joanne D; Mullins, James I; Holte, Sarah E

    2016-01-01

    Availability of integrase strand transfer inhibitors created interest in determining whether their use would decrease persistently infected cell numbers. This study hypothesized that adding raltegravir (RAL) to standard antiretroviral therapy (ART) would decrease human immunodeficiency virus (HIV)-infected CD4(+) T cells more than standard combination ART. This was a pilot, randomized study comparing open-label standard triple ART to standard triple ART plus RAL over 96 weeks in ART-naive adults with early HIV infection. The primary objective was to compare quantity and trajectory of HIV DNA. Eighty-two persons were referred. A diverse set of reasons precluded the enrollment of all but 10. Those who enrolled and completed the study had an estimated median duration of HIV infection of 74 days at ART start. The groups had similar baseline characteristics. The RAL group had more rapid first phase plasma HIV RNA decay (0.67 log10 copies/mL/day) than with combination ART (0.34 log10copies/mL/day), p = 0.037. Second phase HIV RNA decay, residual viremia, cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circle levels did not differ between groups. Among those with entry plasma HIV RNA levels above the median, 2LTR circles were significantly lower over time than in those with lower entry HIV RNA levels (p = 0.02). Our results suggest homogeneity of responses in cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circles with early HIV in both ART groups. The kinetics of 2LTR DNA did not reflect the kinetics of plasma HIV RNA decline following ART initiation. PMID:26862469

  11. Defective virus is associated with induction of murine retrovirus-induced immunodeficiency syndrome.

    PubMed Central

    Chattopadhyay, S K; Morse, H C; Makino, M; Ruscetti, S K; Hartley, J W

    1989-01-01

    C57BL/6 mice infected with a mixture of murine leukemia viruses (MuLV) develop a syndrome characterized by lymphoproliferation and profound immunodeficiency. Analyses of this viral mixture (LP-BM5 MuLV) showed that it includes replication-competent ecotropic and mink cell focus-inducing MuLV and defective viruses with genome sizes of 3.8-6.5 kilobases. The ecotropic and mink cell focus-inducing MuLV biologically cloned from the mixture did not induce disease, whereas viral preparations containing the ecotropic MuLV and 4.8-kilobase defective virus were active. Cells producing the 4.8-kilobase defective virus expressed an unusual gag-encoded polyprotein of Mr 60,000. Images PMID:2542949

  12. Plaque staining assay for non- or weakly cytotoxic human immunodeficiency virus.

    PubMed

    Matsui, T; Nakashima, H; Yoshiyama, H; Kobayashi, N; Yamamoto, N

    1987-07-01

    Cells infected with human immunodeficiency virus (HIV) were selectively stained with peroxidase-coupled antibodies in a recently developed plaque assay for HIV. The numbers of plaques formed with the human T-cell lymphotropic virus type III strain of HIV were exactly the same in stained (immunologically detectable) and unstained (visible) dishes. However, four times more plaques were visualized in stained dishes than in unstained dishes when the YU-6 and acquired immune deficiency syndrome-associated retrovirus strains of HIV were used. Linear relationship was observed between the number of stained plaques and the virus concentrations in the titration of human T-cell lymphotropic virus type III and YU-6. The assay should be useful for the titration of HIV, especially for non- or weakly cytopathic strains of HIV.

  13. Ongoing Clinical Trials of Human Immunodeficiency Virus Latency-Reversing and Immunomodulatory Agents

    PubMed Central

    Delagrèverie, Héloïse M.; Delaugerre, Constance; Lewin, Sharon R.; Deeks, Steven G.; Li, Jonathan Z.

    2016-01-01

    In chronic human immunodeficiency virus (HIV)-1 infection, long-lived latently infected cells are the major barrier to virus eradication and functional cure. Several therapeutic strategies to perturb, eliminate, and/or control this reservoir are now being pursued in the clinic. These strategies include latency reversal agents (LRAs) designed to reactivate HIV-1 ribonucleic acid transcription and virus production and a variety of immune-modifying drugs designed to reverse latency, block homeostatic proliferation, and replenish the viral reservoir, eliminate virus-producing cells, and/or control HIV replication after cessation of antiretroviral therapy. This review provides a summary of ongoing clinical trials of HIV LRAs and immunomodulatory molecules, and it highlights challenges in the comparison and interpretation of the expected trial results. PMID:27757411

  14. Quality of different in-clinic test systems for feline immunodeficiency virus and feline leukaemia virus infection.

    PubMed

    Hartmann, Katrin; Griessmayr, Pascale; Schulz, Bianka; Greene, Craig E; Vidyashankar, Anand N; Jarrett, Os; Egberink, Herman F

    2007-12-01

    Many new diagnostic in-house tests for identification of feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) infection have been licensed for use in veterinary practice, and the question of the relative merits of these kits has prompted comparative studies. This study was designed to define the strengths and weaknesses of seven FIV and eight FeLV tests that are commercially available. In this study, 536 serum samples from randomly selected cats were tested. Those samples reacting FIV-positive in at least one of the tests were confirmed by Western blot, and those reacting FeLV-positive were confirmed by virus isolation. In addition, a random selection of samples testing negative in all test systems was re-tested by Western blot (100 samples) and by virus isolation (81 samples). Specificity, sensitivity, positive and negative predictive values of each test and the quality of the results were compared.

  15. Fangchinoline Inhibits Human Immunodeficiency Virus Type 1 Replication by Interfering with gp160 Proteolytic Processing

    PubMed Central

    Wan, Zhitao; Lu, Yimei; Liao, Qingjiao; Wu, Yang; Chen, Xulin

    2012-01-01

    The introduction of highly active antiretroviral therapy has led to a significant reduction in the morbidity and mortality of acquired immunodeficiency syndrome patients. However, the emergence of drug resistance has resulted in the failure of treatments in large numbers of patients and thus necessitates the development of new classes of anti-HIV drugs. In this study, more than 200 plant-derived small-molecule compounds were evaluated in a cell-based HIV-1 antiviral screen, resulting in the identification of a novel HIV-1 inhibitor (fangchinoline). Fangchinoline, a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae, exhibited antiviral activity against HIV-1 laboratory strains NL4-3, LAI and BaL in MT-4 and PM1 cells with a 50% effective concentration ranging from 0.8 to 1.7 µM. Mechanism-of-action studies showed that fangchinoline did not exhibit measurable antiviral activity in TZM-b1 cells but did inhibit the production of infectious virions in HIV-1 cDNA transfected 293T cells, which suggests that the compound targets a late event in infection cycle. Furthermore, the antiviral effect of fangchinoline seems to be HIV-1 enve1ope-dependent, as the production of infectious HIV-1 particles packaged with a heterologous envelope, the vesicular stomatitis virus G glycoprotein, was unaffected by fangchinoline. Western blot analysis of HIV envelope proteins expressed in transfected 293T cells and in isolated virions showed that fangchinoline inhibited HIV-1 gp160 processing, resulting in reduced envelope glycoprotein incorporation into nascent virions. Collectively, our results demonstrate that fangchinoline inhibits HIV-1 replication by interfering with gp160 proteolytic processing. Fangchinoline may serve as a starting point for developing a new HIV-1 therapeutic approach. PMID:22720080

  16. Fangchinoline inhibits human immunodeficiency virus type 1 replication by interfering with gp160 proteolytic processing.

    PubMed

    Wan, Zhitao; Lu, Yimei; Liao, Qingjiao; Wu, Yang; Chen, Xulin

    2012-01-01

    The introduction of highly active antiretroviral therapy has led to a significant reduction in the morbidity and mortality of acquired immunodeficiency syndrome patients. However, the emergence of drug resistance has resulted in the failure of treatments in large numbers of patients and thus necessitates the development of new classes of anti-HIV drugs. In this study, more than 200 plant-derived small-molecule compounds were evaluated in a cell-based HIV-1 antiviral screen, resulting in the identification of a novel HIV-1 inhibitor (fangchinoline). Fangchinoline, a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae, exhibited antiviral activity against HIV-1 laboratory strains NL4-3, LAI and BaL in MT-4 and PM1 cells with a 50% effective concentration ranging from 0.8 to 1.7 µM. Mechanism-of-action studies showed that fangchinoline did not exhibit measurable antiviral activity in TZM-b1 cells but did inhibit the production of infectious virions in HIV-1 cDNA transfected 293T cells, which suggests that the compound targets a late event in infection cycle. Furthermore, the antiviral effect of fangchinoline seems to be HIV-1 envelope-dependent, as the production of infectious HIV-1 particles packaged with a heterologous envelope, the vesicular stomatitis virus G glycoprotein, was unaffected by fangchinoline. Western blot analysis of HIV envelope proteins expressed in transfected 293T cells and in isolated virions showed that fangchinoline inhibited HIV-1 gp160 processing, resulting in reduced envelope glycoprotein incorporation into nascent virions. Collectively, our results demonstrate that fangchinoline inhibits HIV-1 replication by interfering with gp160 proteolytic processing. Fangchinoline may serve as a starting point for developing a new HIV-1 therapeutic approach. PMID:22720080

  17. U-90152, a potent inhibitor of human immunodeficiency virus type 1 replication.

    PubMed Central

    Dueweke, T J; Poppe, S M; Romero, D L; Swaney, S M; So, A G; Downey, K M; Althaus, I W; Reusser, F; Busso, M; Resnick, L

    1993-01-01

    Bisheteroarylpiperazines are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). We describe a novel bisheteroarylpiperazine, U-90152 [1-(5-methanesulfonamido-1H-indol-2-yl-carbonyl)-4-[3-(1-methyl eth yl-amino)pyridinyl]piperazine], which inhibited recombinant HIV-1 RT at a 50% inhibitory concentration (IC50) of 0.26 microM (compared with IC50s of > 440 microM for DNA polymerases alpha and delta). U-90152 blocked the replication in peripheral blood lymphocytes of 25 primary HIV-1 isolates, including variants that were highly resistant to 3'-azido-2',3'-dideoxythymidine (AZT) or 2',3'-dideoxyinosine, with a mean 50% effective dose of 0.066 +/- 0.137 microM. U-90152 had low cellular cytotoxicity, causing less than 8% reduction in peripheral blood lymphocyte viability at 100 microM. In experiments assessing inhibition of the spread of HIV-1IIIB in cell cultures, U-90152 was much more effective than AZT. When approximately 500 HIV-1IIIB-infected MT-4 cells were mixed 1:1,000 with uninfected cells, 3 microM AZT delayed the evidence of rapid viral growth for 7 days. In contrast, 3 microM U-90152 totally prevented the spread of HIV-1, and death and/or dilution of the original inoculum of infected cells prevented renewed viral growth after U-90152 was removed at day 24. The combination of U-90152 and AZT, each at 0.5 microM, also totally prevented viral spread. Finally, although the RT amino acid substitutions K103N (lysine 103 to asparagine) and Y181C (tyrosine 181 to cysteine), which confer cross-resistance to several nonnucleoside inhibitors, also decrease the potency of U-90152, this drug retains significant activity against these mutant RTs in vitro (IC50s, approximately 8 microgramM). PMID:7685995

  18. Intrapatient sequence variation of the gag gene of human immunodeficiency virus type 1 plasma virions.

    PubMed Central

    Yoshimura, F K; Diem, K; Learn, G H; Riddell, S; Corey, L

    1996-01-01

    Because certain regions of the gag gene, such as p24, are highly conserved among human immunodeficiency virus (HIV) isolates, many therapeutic strategies have been directed at gag gene targets. Although intrapatient variation of segments of gag have been determined, little is known about the variability of the full-length gag gene for HIV isolated from a single individual. To evaluate intrapatient full-length gag variability, we derived the nucleotide sequences of at least 10 cDNA gag clones of virion RNA isolated from plasma for each of four asymptomatic HIV type 1-infected patients with relatively high CD4+ T-cell counts (300 to 450 cells per mm3). Mean values of intrapatient gag nucleotide variation obtained by pairwise comparisons ranged from 0.55 to 2.86%. For three subjects, this value was equivalent to that reported for intrapatient full-length env variation. The greatest range of intrapatient mean nucleotide variation for individual protein-coding regions was observed for p7. We did not detect any G-to-A hypermutation, as A-to-G and G-to-A transitions occurred at similar frequencies, accounting for 29 and 25%, respectively, of the changes. Mean variation values and phylogenetic analysis suggested that the extent of nucleotide variation correlated with the length of viral infection. Furthermore, no distinct subpopulations of quasispecies were detectable within an individual. The predicted amino acid sequences indicated that there were no regions within a gag protein that were comprised of clustered changes. PMID:8971017

  19. The Remarkable Frequency of Human Immunodeficiency Virus Type 1 Genetic Recombination

    PubMed Central

    Onafuwa-Nuga, Adewunmi; Telesnitsky, Alice

    2009-01-01

    Summary: The genetic diversity of human immunodeficiency virus type 1 (HIV-1) results from a combination of point mutations and genetic recombination, and rates of both processes are unusually high. This review focuses on the mechanisms and outcomes of HIV-1 genetic recombination and on the parameters that make recombination so remarkably frequent. Experimental work has demonstrated that the process that leads to recombination—a copy choice mechanism involving the migration of reverse transcriptase between viral RNA templates—occurs several times on average during every round of HIV-1 DNA synthesis. Key biological factors that lead to high recombination rates for all retroviruses are the recombination-prone nature of their reverse transcription machinery and their pseudodiploid RNA genomes. However, HIV-1 genes recombine even more frequently than do those of many other retroviruses. This reflects the way in which HIV-1 selects genomic RNAs for coencapsidation as well as cell-to-cell transmission properties that lead to unusually frequent associations between distinct viral genotypes. HIV-1 faces strong and changeable selective conditions during replication within patients. The mode of HIV-1 persistence as integrated proviruses and strong selection for defective proviruses in vivo provide conditions for archiving alleles, which can be resuscitated years after initial provirus establishment. Recombination can facilitate drug resistance and may allow superinfecting HIV-1 strains to evade preexisting immune responses, thus adding to challenges in vaccine development. These properties converge to provide HIV-1 with the means, motive, and opportunity to recombine its genetic material at an unprecedented high rate and to allow genetic recombination to serve as one of the highest barriers to HIV-1 eradication. PMID:19721086

  20. Normal T-Cell Turnover in Sooty Mangabeys Harboring Active Simian Immunodeficiency Virus Infection

    PubMed Central

    Chakrabarti, Lisa A.; Lewin, Sharon R.; Zhang, Linqi; Gettie, Agegnehu; Luckay, Amara; Martin, Louis N.; Skulsky, Eva; Ho, David D.; Cheng-Mayer, Cecilia; Marx, Preston A.

    2000-01-01

    Sooty mangabeys naturally infected with simian immunodeficiency virus (SIV) remain healthy though they harbor viral loads comparable to those in rhesus macaques that progress to AIDS. To assess the immunologic basis of disease resistance in mangabeys, we compared the effect of SIV infection on T-cell regeneration in both monkey species. Measurement of the proliferation marker Ki-67 by flow cytometry showed that mangabeys harbored proliferating T cells at a level of 3 to 4% in peripheral blood irrespective of their infection status. In contrast, rhesus macaques demonstrated a naturally high fraction of proliferating T cells (7%) that increased two- to threefold following SIV infection. Ki-67+ T cells were predominantly CD45RA−, indicating increased proliferation of memory cells in macaques. Quantitation of an episomal DNA product of T-cell receptor α rearrangement (termed α1 circle) showed that the concentration of recent thymic emigrants in blood decreased with age over a 2-log unit range in both monkey species, consistent with age-related thymic involution. SIV infection caused a limited decrease of α1 circle numbers in mangabeys as well as in macaques. Dilution of α1 circles by T-cell proliferation likely contributed to this decrease, since α1 circle numbers and Ki-67+ fractions correlated negatively. These findings are compatible with immune exhaustion mediated by abnormal T-cell proliferation, rather than with early thymic failure, in SIV-infected macaques. Normal T-cell turnover in SIV-infected mangabeys provides an explanation for the long-term maintenance of a functional immune system in these hosts. PMID:10627531

  1. Temporal patterns of human immunodeficiency virus type 1 transcripts in human fetal astrocytes.

    PubMed Central

    Tornatore, C; Meyers, K; Atwood, W; Conant, K; Major, E

    1994-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection of the developing central nervous system results in a dementing process in children, termed HIV-1-associated encephalopathy. Infection of astroglial elements of the pediatric nervous system has been demonstrated and suggests that direct infection of some astrocytes may contribute to the neurologic deficit. In this model, HIV-1 establishes a persistent state of infection in astrocytes, which can be reactivated by the cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta). To better understand the natural history of viral persistence in astroglial cells, we characterized infection at the transcriptional level. The most abundant viral transcript during the establishment of persistence was the subgenomic multiply spliced 2-kb message, similar to mononuclear cell models of HIV-1 latency. Following reactivation with TNF-alpha or IL-1 beta the multiply spliced 2-kb message remained the most abundant viral transcript, in contrast to infected mononuclear cells in which reactivation leads to the reemergence of the 9- and 4-kb transcripts. Further characterization of the persistent 2-kb transcript by PCR amplification of in vitro-synthesized viral cDNA showed that, in the absence of cytokine stimulation, the most abundant multiply spliced transcripts were the Nef- and Rev-specific messages. However, following cytokine stimulation, double- and triple-spliced Tat-, Rev-, and Nef-specific messages could be identified. Immunohistochemical staining demonstrated that, during viral persistence, astrocytes expressed Nef protein but few or no viral structural proteins. These results demonstrate that viral persistence in astrocytes at the transcriptional level is fundamentally different from that seen in mononuclear cells and could account for the virtual absence of astroglial expression of viral structural antigens in vivo. Images PMID:8254781

  2. The remarkable frequency of human immunodeficiency virus type 1 genetic recombination.

    PubMed

    Onafuwa-Nuga, Adewunmi; Telesnitsky, Alice

    2009-09-01

    The genetic diversity of human immunodeficiency virus type 1 (HIV-1) results from a combination of point mutations and genetic recombination, and rates of both processes are unusually high. This review focuses on the mechanisms and outcomes of HIV-1 genetic recombination and on the parameters that make recombination so remarkably frequent. Experimental work has demonstrated that the process that leads to recombination--a copy choice mechanism involving the migration of reverse transcriptase between viral RNA templates--occurs several times on average during every round of HIV-1 DNA synthesis. Key biological factors that lead to high recombination rates for all retroviruses are the recombination-prone nature of their reverse transcription machinery and their pseudodiploid RNA genomes. However, HIV-1 genes recombine even more frequently than do those of many other retroviruses. This reflects the way in which HIV-1 selects genomic RNAs for coencapsidation as well as cell-to-cell transmission properties that lead to unusually frequent associations between distinct viral genotypes. HIV-1 faces strong and changeable selective conditions during replication within patients. The mode of HIV-1 persistence as integrated proviruses and strong selection for defective proviruses in vivo provide conditions for archiving alleles, which can be resuscitated years after initial provirus establishment. Recombination can facilitate drug resistance and may allow superinfecting HIV-1 strains to evade preexisting immune responses, thus adding to challenges in vaccine development. These properties converge to provide HIV-1 with the means, motive, and opportunity to recombine its genetic material at an unprecedented high rate and to allow genetic recombination to serve as one of the highest barriers to HIV-1 eradication.

  3. Repeated exposure of rhesus macaques to low doses of simian immunodeficiency virus (SIV) did not protect them against the consequences of a high-dose SIV challenge.

    PubMed

    Dittmer, U; Stahl-Hennig, C; Coulibaly, C; Nisslein, T; Lüke, W; Fuchs, D; Bodemer, W; Petry, H; Hunsmann, G

    1995-06-01

    As part of an in vivo titration study of the macaque simian immunodeficiency virus (SIVmac) strain 251/spl, macaques were inoculated intravenously with various dilutions of this infectious SIVmac. Seven animals received dilutions from 10(-3) to 10(-6) of SIVmac251/spl. Two monkeys infected with the 10(-3) dilution of SIVmac exhibited a productive infection as indicated by seroconversion, detection of genomic RNA and proviral DNA and positive virus isolation. These animals showed a cytotoxic T cell (CTL) response against different SIVmac proteins without any measurable T cell proliferation. The five macaques receiving higher virus dilutions did not seroconvert and were negative for both viral RNA and for infectious virus, although proviral DNA was detected in their peripheral blood mononuclear cells. In contrast to the animals receiving the 10(-3) virus dilution, these five silently infected monkeys developed an SIV-specific proliferative T cell response but SIV-specific CTL could not be observed. The SIV-specific T cell proliferation of the silently infected animals could be boosted by a second low-dose exposure with a 10(-4) or 10(-5) dilution of SIVmac251/spl. The virological status of the animals was not changed following this second virus inoculation. Four months later these macaques were challenged intravenously with 2 ml of a 10(-4) dilution of SIVmac251/32H containing 10 monkey ID50. After this challenge all SIV-pre-exposed animals and three naive controls became productively infected. In addition, all infected animals developed typical signs of an immunodeficiency within 6 months after infection. These observations indicate that macaques infected silently by a low-dose exposure to infectious virus generated a virus-specific cellular immune response. However, SIV-specific T cell proliferation alone could not protect the monkeys against an intravenous challenge with SIVmac and the subsequent development of AIDS-like symptoms.

  4. PD 404,182 Is a Virocidal Small Molecule That Disrupts Hepatitis C Virus and Human Immunodeficiency Virus

    PubMed Central

    Chamoun, Ana Maria; Chockalingam, Karuppiah; Bobardt, Michael; Simeon, Rudo; Chang, Jinhong

    2012-01-01

    We describe a virucidal small molecule, PD 404,182, that is effective against hepatitis C virus (HCV) and human immunodeficiency virus (HIV). The median 50% inhibitory concentrations (IC50s) for the antiviral effect of PD 404,182 against HCV and HIV in cell culture are 11 and 1 μM, respectively. The antiviral activity of PD 404,182 is due to the physical disruption of virions that is accompanied to various degrees (depending on the virus and exposure temperature/time) by the release of viral nucleic acids into the surrounding medium. PD 404,182 does not directly lyse liposomal membranes even after extended exposure, and it shows no attenuation in antiviral activity when preincubated with liposomes of various lipid compositions, suggesting that the compound inactivates viruses through interaction with a nonlipid structural component of the virus. The virucidal activity of PD 404,182 appears to be virus specific, as little to no viral inactivation was detected with the enveloped Dengue and Sindbis viruses. PD 404,182 effectively inactivates a broad range of primary isolates of HIV-1 as well as HIV-2 and simian immunodeficiency virus (SIV), and it does not exhibit significant cytotoxicity with multiple human cell lines in vitro (50% cytotoxic concentration, >300 μM). The compound is fully active in cervical fluids, although it exhibits decreased potency in the presence of human serum, retains its full antiviral potency for 8 h when in contact with cells, and is effective against both cell-free and cell-associated HIV. These qualities make PD 404,182 an attractive candidate anti-HIV microbicide for the prevention of HIV transmission through sexual intercourse. PMID:22083468

  5. Structure of large dsDNA viruses

    PubMed Central

    Klose, Thomas; Rossmann, Michael G.

    2015-01-01

    Nucleocytoplasmic large dsDNA viruses (NCLDVs) encompass an ever-increasing group of large eukaryotic viruses, infecting a wide variety of organisms. The set of core genes shared by all these viruses includes a major capsid protein with a double jelly-roll fold forming an icosahedral capsid, which surrounds a double layer membrane that contains the viral genome. Furthermore, some of these viruses, such as the members of the Mimiviridae and Phycodnaviridae have a unique vertex that is used during infection to transport DNA into the host. PMID:25003382

  6. Chimeric gag-V3 virus-like particles of human immunodeficiency virus induce virus-neutralizing antibodies.

    PubMed Central

    Luo, L; Li, Y; Cannon, P M; Kim, S; Kang, C Y

    1992-01-01

    A 41-kDa unprocessed human immunodeficiency virus 2 (HIV-2) gag precursor protein that has a deletion of a portion of the viral protease assembles as virus-like particles by budding through the cytoplasmic membrane of recombinant baculovirus-infected insect cells. We have constructed six different combinations of chimeric genes by coupling the truncated HIV-2 gag gene to the neutralizing domain (V3) or the neutralizing and the CD4 binding domains (V3+CD4BD) of gp120 env gene sequences from HIV-1 or HIV-2. The env gene sequences were inserted either into the middle of the gag gene or at the 3' terminus of the gag gene. Virus-like particles were formed by chimeric gene products only when the env gene sequences were linked to the 3' terminus of the gag gene. Insertion of env gene sequence in the middle of the gag gene resulted in high-level chimeric gene expression but without the formation of virus-like particles. Three different chimeric genes [gag gene with HIV-1 V3 (1V3), gag gene with HIV-2 V3 (2V3), and gag gene with HIV-2 V3+CD4BD (2V3+CD4BD)] formed virus-like particles that were secreted into the cell culture medium. In contrast, the HIV-1 V3+CD4BD/HIV-2 gag construct did not form virus-like particles. The chimeric gag-env particles had spherical morphology and the size was slightly larger than that of the gag particles, but the chimeric particles were similar to the mature HIV particles. Western blot analysis showed that the gag-env chimeric proteins were recognized by antibodies in HIV-positive human serum and rabbit anti-gp120 serum. Rabbit anti-gag 1V3 and anti-gag 2V3 sera reacted with authentic gp120 of HIV-1 and HIV-2, respectively, and neutralized homologous HIV infectivity. Our results show that precursor gag protein has potential as a carrier for the presentation of foreign epitopes in good immunological context. The gag protein is highly immunogenic and has the ability to carry large foreign inserts; as such, it offers an attractive approach for

  7. Adaptive evolution of simian immunodeficiency viruses isolated from two conventional progressor macaques with neuroaids

    SciTech Connect

    Foley, Brian T; Korber, Bette T

    2008-01-01

    Simian immunodeficiency virus infection of macaques may result in neuroAIDS, a feature more commonly observed in macaques with rapid progressive disease than in those with conventional disease. This is the first report of two conventional progressors (H631 and H636) with encephalitis in rhesus macaques inoculated with a derivative of SIVsmES43-3. Phylogenetic analyses of viruses isolated from the cerebral spinal fluid (CSF) and plasma from both animals demonstrated tissue compartmentalization. Additionally, virus from the central nervous system (CNS) was able to infect primary macaque monocyte-derived macrophages more efficiently than virus from plasma. Conversely, virus isolated from plasma was able to replicate better in peripheral blood mononuclear cells than virus from CNS. We speculate that these viruses were under different selective pressures in their separate compartments. Furthermore, these viruses appear to have undergone adaptive evolution to preferentially replicate in their respective cell targets. Analysis of the number of potential N-linked glycosylation sites (PNGS) in gp160 showed that there was a statistically significant loss of PNGS in viruses isolated from CNS in both macaques compared to SIVsmE543-3. Moreover, virus isolated from the brain in H631, had statistically significant loss of PNGS compared to virus isolated from CSF and plasma of the same animal. It is possible that the brain isolate may have adapted to decrease the number of PNGS given that humoral immune selection pressure is less likely to be encountered in the brain. These viruses provide a relevant model to study the adaptations required for SIV to induce encephalitis.

  8. Detection of pseudorabies virus by DNA hybridization

    SciTech Connect

    McFarlane, R.G.

    1985-01-01

    A DNA hybridization technique was developed in order to detect the presence of pseudorabies virus (PRV) deoxyribonucleic acid (DNA) in swine tissue. Seven, /sup 32/P-nick translated probes of high specific activity were prepared from transformed Escherichia coli plasmids into which Bacillus amyloliquefaciens H (Bam H1) restriction fragments of PRV-DNA had been inserted. Under optimal hybridization conditions, the minimum detection level of PRV-DNA was 10/sup -11/ g, which is equivalent to 1 copy of the PRV genome/80 host cells. PRV-DNA was detected in the DNA extracted from the tissues of 10 out of 11 swine previously shown to harbor infective virus. Furthermore, PRV-DNA was present in all four seropositive swine that had recovered from pseudorabies, where no infective virus or viral products were detected at necropsy. The PRV-DNA was present in either the anterior cerebral cortex in 2 swine, or the medulla oblongata and trigeminal ganglion in 1 swine. This perhaps indicates the portal of entry of the virus into the central nervous system. This DNA hybridization assay, which utilizes restriction fragments, may be useful for studying the dynamics and molecular biologic properties of the latency of pseudorabies virus in swine.

  9. Inhibition of growth of human immunodeficiency virus in vitro by crude extracts of Chinese medicinal herbs.

    PubMed

    Chang, R S; Yeung, H W

    1988-04-01

    Twenty-seven medicinal herbs reputed in ancient Chinese folklore to have anti-infective properties were extracted by boiling under reflux. The extracts were tested for inhibitory activity against the human immunodeficiency virus in the H9 cell line at concentrations nontoxic to growth of the H9 cells. Using a significant reduction (greater than 3 S. D. below the mean) in the percentage of cells positive for specific viral antigens in three successive assays as indicative of activity against the virus, 11 of the 27 extracts were found to be active. One of the extracts (Viola yedoensis) was studied in greater depth. At a subtoxic concentration, this extract shut off completely the growth of HIV in virtually all experiments. It did not inactivate HIV extracellularly, did not induce interferon and did not inhibit the growth of herpes simplex, polio or vesicular stomatitis viruses in human fibroblast culture. Chinese medicinal herbs appeared to be a rich source of potentially useful materials for the treatment of human immunodeficiency virus infection. PMID:2840849

  10. Interleukin-16 Inhibits Human Immunodeficiency Virus Type 1 Entry and Replication in Macrophages and in Dendritic Cells

    PubMed Central

    Truong, Marie-Jose; Darcissac, Edith C. A.; Hermann, Emmanuel; Dewulf, Joelle; Capron, Andre; Bahr, George M.

    1999-01-01

    Recombinant interleukin-16 (rIL-16) has been found to inhibit human immunodeficiency virus type 1 (HIV-1) replication in acutely or endogenously infected CD4+ T cells. However, the effect of rIL-16 on HIV-1 replication in antigen-presenting cells (APCs) is still unknown. We show here a potent HIV-suppressive activity of rIL-16 in acutely infected monocyte-derived macrophages and dendritic cells determined by the levels of viral RNA transcripts or of viral reverse transcriptase in culture supernatants. The observed effect was dependent on the presence of rIL-16 early after infection and could not be induced by a 24-h treatment of cells with the cytokine prior to infection. Using macrophage-tropic and dually tropic primary isolates, we also showed that the addition of rIL-16 to cell cultures only during the infection period was effective in blocking virus entry and reducing proviral DNA levels in APCs. However, the anti-HIV activity of rIL-16 could not be linked to the induction of virus-suppressive concentrations of β-chemokines or to the inhibition of HIV-enhancing cytokines. These findings establish a critical role for rIL-16 in protecting APCs against HIV-1 infection and lend further support to its potential use in the treatment of HIV disease. PMID:10400800

  11. Identification of Light-independent Inhibition of Human Immunodeficiency Virus-1 Infection through Bioguided Fractionation of Hypericum perforatum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Light-dependent activities against enveloped viruses in St. John's Wort (Hypericum perforatum) extracts have been extensively studied. In contrast, light-independent antiviral activity from this species has not. Here, we identify the light-independent inhibition of human immunodeficiency virus-1 (...

  12. Identification of three feline immunodeficiency virus (FIV) env gene subtypes and comparison of the FIV and human immunodeficiency virus type 1 evolutionary patterns.

    PubMed Central

    Sodora, D L; Shpaer, E G; Kitchell, B E; Dow, S W; Hoover, E A; Mullins, J I

    1994-01-01

    Feline immunodeficiency virus (FIV) is a lentivirus associated with AIDS-like illnesses in cats. As such, FIV appears to be a feline analog of human immunodeficiency virus (HIV). A hallmark of HIV infection is the large degree of viral genetic diversity that can develop within an infected individual and the even greater and continually increasing level of diversity among virus isolates from different individuals. Our goal in this study was to determine patterns of FIV genetic diversity by focusing on a 684-nucleotide region encompassing variable regions V3, V4, and V5 of the FIV env gene in order to establish parallels and distinctions between FIV and HIV type 1 (HIV-1). Our data demonstrate that, like HIV-1, FIV can be separated into distinct envelope sequence subtypes (three are described here). Similar to that found for HIV-1, the pairwise sequence divergence within an FIV subtype ranged from 2.5 to 15.0%, whereas that between subtypes ranged from 17.8 to 26.2%. However, the high number of synonymous nucleotide changes among FIV V3 to V5 env sequences may also include a significant number of back mutations and suggests that the evolutionary distances among FIV subtypes are underestimated. Although only a few subtype B viruses were available for examination, the pattern of diversity between the FIV A and B subtypes was found to be significantly distinct; subtype B sequences had proportionally fewer mutations that changed amino acids, compared with silent changes, suggesting a more advanced state of adaptation to the host. No similar distinction was evident for HIV-1 subtypes. The diversity of FIV genomes within individual infected cats was found to be as high as 3.7% yet twofold lower than that within HIV-1-infected people over a comparable region of the env gene. Despite these differences, significant parallels between patterns of FIV evolution and HIV-1 evolution exist, indicating that a wide array of potentially divergent virus challenges need to be considered

  13. In vivo compartmentalization of human immunodeficiency virus: evidence from the examination of pol sequences from autopsy tissues.

    PubMed Central

    Wong, J K; Ignacio, C C; Torriani, F; Havlir, D; Fitch, N J; Richman, D D

    1997-01-01

    High rates of mutation and replication of human immunodeficiency virus (HIV) allow for the continuous generation of diverse genetic variants in vivo. Selective pressures within the microenvironments of different anatomic compartments result in the emergence of dominant quasispecies which can be distinguished by their envelope sequences. It is not known whether comparable tissue-specific selective pressures lead to the independent evolution of pol sequences within different tissue compartments, nor is it known how differing rates of virus turnover in tissues might affect the pace of such evolution. These issues are of importance for the formulation of a model for the emergence of drug resistance in vivo and for a general understanding of virus trafficking and virus turnover. Regions of the HIV type 1 reverse transcriptase (RT) which carry the majority of the known resistance codons to RT inhibitors (700 nucleotides from each clone) were cloned and sequenced directly from autopsied brain, spleen, and lymph node specimens from four subjects who had received zidovudine therapy. Clones from proviral DNA (143) and from viral cDNA (14) were analyzed. In three of four subjects, a discordance in distribution of resistance codons was noted. Moreover, brain-derived sequences appeared to be phylogenetically distinct from spleen- and lymph node-derived sequences even after exclusion of resistance codons from analysis. In each case, evidence for differential immune selective pressure, based on comparison of inferred amino acid sequences corresponding to known major histocompatibility complex class I cytotoxic T-lymphocyte epitopes, was found. These observations support the concept of anatomically distinct, independently evolving quasispecies (virodemes). PMID:9032338

  14. Epstein-Barr virus and human immunodeficiency virus serological responses and viral burdens in HIV-infected patients treated with HAART

    NASA Technical Reports Server (NTRS)

    O'Sullivan, Cathal E.; Peng, RongSheng; Cole, Kelly Stefano; Montelaro, Ronald C.; Sturgeon, Timothy; Jenson, Hal B.; Ling, Paul D.; Butel, J. S. (Principal Investigator)

    2002-01-01

    Epstein-Barr virus (EBV) associated non-Hodgkin lymphoma is recognized as a complication of human immunodeficiency virus (HIV) infection. Little is known regarding the influence of highly active antiretroviral therapy (HAART) on the biology of EBV in this population. To characterize the EBV- and HIV-specific serological responses together with EBV DNA levels in a cohort of HIV-infected adults treated with HAART, a study was conducted to compare EBV and HIV serologies and EBV DNA copy number (DNAemia) over a 12-month period after the commencement of HAART. All patients were seropositive for EBV at baseline. Approximately 50% of patients had detectable EBV DNA at baseline, and 27/30 had detectable EBV DNA at some point over the follow-up period of 1 year. Changes in EBV DNA copy number over time for any individual were unpredictable. Significant increases in the levels of Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr early antigen (EA) antibodies were demonstrated in the 17 patients who had a good response to HAART. Of 29 patients with paired samples tested, four-fold or greater increases in titers were detected for EA in 12/29 (41%), for EBNA in 7/29 (24%), for VCA-IgG in 4/29 (14%); four-fold decreases in titers were detected in 2/29 (7%) for EA and 12/29 (41%) for EBNA. A significant decline in the titer of anti-HIV antibodies was also demonstrated. It was concluded that patients with advanced HIV infection who respond to HAART have an increase in their EBV specific antibodies and a decrease in their HIV-specific antibodies. For the cohort overall, there was a transient increase in EBV DNA levels that had declined by 12 months. Copyright 2002 Wiley-Liss, Inc.

  15. A lion lentivirus related to feline immunodeficiency virus: epidemiologic and phylogenetic aspects.

    PubMed Central

    Brown, E W; Yuhki, N; Packer, C; O'Brien, S J

    1994-01-01

    Feline immunodeficiency virus (FIV) is a novel lentivirus that is genetically homologous and functionally analogous to the human AIDS viruses, human immunodeficiency virus types 1 and 2. FIV causes immunosuppression in domestic cats by destroying the CD4 T-lymphocyte subsets in infected hosts. A serological survey of over 400 free-ranging African and Asian lions (Panthera leo) for antibodies to FIV revealed endemic lentivirus prevalence with an incidence of seropositivity as high as 90%. A lion lentivirus (FIV-Ple) was isolated by infection of lion lymphocytes in vitro. Seroconversion was documented in two Serengeti lions, and discordance of mother-cub serological status argues against maternal transmission (in favor of horizontal spread) as a major route of infection among lions. A phylogenetic analysis of cloned FIV-Ple pol gene sequences from 27 lions from four African populations (from the Serengeti reserve, Ngorongoro Crater, Lake Manyara, and Kruger Park) revealed remarkably high intra- and interindividual genetic diversity at the sequence level. Three FIV-Ple phylogenetic clusters or clades were resolved with phenetic, parsimony, and likelihood analytical procedures. The three clades, which occurred not only together in the same population but throughout Africa, were as divergent from each other as were homologous pol sequences of lentivirus isolated from distinct feline species, i.e., puma and domestic cat. The FIV-Ple clades, however, were more closely related to each other than to other feline lentiviruses (monophyletic for lion species), suggesting that the ancestors of FIV-Ple evolved in allopatric (geographically isolated) lion populations that converged recently. To date, there is no clear evidence of FIV-Ple-associated pathology, raising the possibility of a historic genetic accommodation of the lion lentivirus and its host leading to a coevolved host-parasite symbiosis (or commensalism) in the population similar to that hypothesized for endemic

  16. [Gastric uptake of gallium67 in the human immunodeficiency virus infection].

    PubMed

    Escalera Temprado, T; Banzo Marraco, J; Abós Olivares, M D; Olave Rubio, M T; Prats Rivera, E; García López, F; Razola Alba, P

    2004-02-01

    Nowadays, the human immunodeficiency virus infection (HIV) is a chronic disease. In the frequent clinical situations with fever, lymph nodes and loss weight it is necessary to determine their etiology, for establishing a specific treatment. Gastrointestinal opportunistic infections or gastric lymphomatous or sarcomatous process, which can accumulate Ga67, may be present in the patient with acquired immunodeficiency syndrome. We report 2 cases with gastric uptake in which endoscopy and biopsy was obtained. In the first one, with previous treatment with omeprazol and almalgate for gastroesophagic reflux, endoscopy and biopsy were normal and in the second patient an Helicobacter pylori infection was diagnosed. We think that gastric uptake of Ga67 in HIV patients, must indicate to the clinician to rule out associated pathologies.

  17. Psychological problems of families and health workers dealing with people infected with human immunodeficiency virus 1.

    PubMed

    Maj, M

    1991-03-01

    The psychological problems of the families of human immunodeficiency virus 1 (HIV-1)-infected people, and of the health workers taking care of them, have been addressed in a few empirical studies and in several anecdotal reports and theoretical contributions. Apparently, HIV-1 infection and acquired immunodeficiency syndrome (AIDS) are able to elicit a wide range of emotional reactions, from rejection and refusal to provide care to immersion in the infected person's needs and burnout. Since irrational fears and attitudes play an important role in conditioning these reactions, education may not be sufficient to change behaviour. Counselling sessions and mutual support groups are often the most appropriate contexts where fears and concerns can receive an individually tailored response, and where formal and informal caregivers can be helped to manage stress.

  18. Genotyping and Molecular Characterization of Hepatitis B Virus from Human Immunodeficiency Virus-Infected Individuals in Southern Africa

    PubMed Central

    Makondo, Euphodia; Bell, Trevor G.; Kramvis, Anna

    2012-01-01

    Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) are hyperendemic in sub-Saharan Africa. The HBV genotypes prevailing in HIV-infected Africans are unknown. Our aim was to determine the HBV genotypes in HIV-infected participants and to identify clinically significant HBV mutations. From 71 HBV DNA+ve HIV-infected participants, 49 basic core promoter/precore (BCP/PC) and 29 complete S regions were successfully sequenced. Following phylogenetic analysis of 29 specimens in the complete S region, 28 belonged to subgenotype A1 and one to D3. Mutations affecting HBeAg expression at the transcriptional (1762T1764A), translational (Kozak 1809–1812, initiation 1814–1816, G1896A with C1858T), or post translational levels (G1862T), were responsible for the high HBeAg-negativity observed. The G1862T mutation occurred only in subgenotype A1 isolates, which were found in one third (7/21) of HBsAg−ve participants, but in none of the 18 HBsAg+ve participants (p<0.05). Pre-S deletion mutants were detected in four HBsAg+ve and one HBsAg−ve participant/s. The following mutations occurred significantly more frequently in HBV isolated in this study than in strains of the same cluster of the phylogenetic tree: ps1F25L, ps1V88L/A; ps2Q10R, ps2 R48K/T, ps2A53V and sQ129R/H, sQ164A/V/G/D, sV168A and sS174N (p<0.05). ps1I48V/T occurred more frequently in females than males (p<0.05). Isolates with sV168A occurred more frequently in participants with viral loads >200 IU per ml (p<0.05) and only sS174N occurred more frequently in HBsAg−ve than in HBsAg+ve individuals (p<0.05). Prior to initiation of ART, ten percent, 3 of 29 isolates sequenced, had drug resistance mutations rtV173L, rtL180M+rtM204V and rtV214A, respectively. This study has provided important information on the molecular characteristics of HBV in HIV-infected southern Africans prior to ART initiation, which has important clinical relevance in the management of HBV/HIV co-infection in our unique setting

  19. Preexisting infection with human T-cell lymphotropic virus type 2 neither exacerbates nor attenuates simian immunodeficiency virus SIVmac251 infection in macaques.

    PubMed

    Gordon, Shari N; Weissman, Anna R; Cecchinato, Valentina; Fenizia, Claudio; Ma, Zhong-Min; Lee, Tzong-Hae; Zaffiri, Lorenzo; Andresen, Vibeke; Parks, Robyn Washington; Jones, Kathryn S; Heraud, Jean Michel; Ferrari, Maria Grazia; Chung, Hye Kyung; Venzon, David; Mahieux, Renaud; Murphy, Edward L; Jacobson, Steven; Miller, Christopher J; Ruscetti, Francis W; Franchini, Genoveffa

    2010-03-01

    Coinfection with human T-cell lymphotropic virus type 2 (HTLV-2) and human immunodeficiency virus type 1 (HIV-1) has been reported to have either a slowed disease course or to have no effect on progression to AIDS. In this study, we generated a coinfection animal model and investigated whether HTLV-2 could persistently infect macaques, induce a T-cell response, and impact simian immunodeficiency virus SIV(mac251)-induced disease. We found that inoculation of irradiated HTLV-2-infected T cells into Indian rhesus macaques elicited humoral and T-cell responses to HTLV-2 antigens at both systemic and mucosal sites. Low levels of HTLV-2 provirus DNA were detected in the blood, lymphoid tissues, and gastrointestinal tracts of infected animals. Exposure of HTLV-2-infected or naïve macaques to SIV(mac251) demonstrated comparable levels of SIV(mac251) viral replication, similar rates of mucosal and peripheral CD4(+) T-cell loss, and increased T-cell proliferation. Additionally, neither the magnitude nor the functional capacity of the SIV-specific T-cell-mediated immune response was different in HTLV-2/SIV(mac251) coinfected animals versus SIV(mac251) singly infected controls. Thus, HTLV-2 targets mucosal sites, persists, and importantly does not exacerbate SIV(mac251) infection. These data provide the impetus for the development of an attenuated HTLV-2-based vectored vaccine for HIV-1; this approach could elicit persistent mucosal immunity that may prevent HIV-1/SIV(mac251) infection.

  20. Metabolic stress in infected cells may represent a therapeutic target for human immunodeficiency virus infection.

    PubMed

    Alonso-Villaverde, Carlos; Menéndez, Javier A; Joven, Jorge

    2013-07-01

    Worldwide, there are thousands of new cases of human immunodeficiency virus-1 (HIV-1) infection per day. The effectiveness of current combination antiretroviral therapy (ART) is relative; to prioritize finding vaccines and/or cure-oriented initiatives should be reinforced because there is little room, if any, for procrastination. Basic and clinical findings on HIV-1 reservoirs suggest that disruption of virus latency is feasible. Because the goal is curing HIV-1 infection, we should be aware that the challenge is to eradicate the viruses of every single infected cell and consequently acting upon virus latency is necessary but not sufficient. The large majority of the virus reservoir, CD4(+) T lymphocytes, is readily accessible but other minor reservoirs, where ART does not diffuse, require innovative strategies. The situation closely resembles that currently faced in the treatment of cancer. Exploiting the fact that histone deacetylase inhibitors, mainly vorinostat, may disrupt the latency of HIV-1, we propose to supplement this effect with a programmed interference in the metabolic stress of infected cells. Metformin and chloroquine are cheap and accessible modulators of pro-survival mechanisms to which viruses are constantly confronted to generate alternative energy sources and maximize virus production. Metformin restrains the use of the usurped cellular biosynthetic machinery by viral genes and chloroquine contributes to death of infected cells. We suggest that the combination of vorinostat, chloroquine and metformin should be combined with ART to pursue viral eradication in infected cells. PMID:23639282

  1. Progressive outer retinal necrosis: manifestation of human immunodeficiency virus infection.

    PubMed

    Lo, Phey Feng; Lim, Rongxuan; Antonakis, Serafeim N; Almeida, Goncalo C

    2015-01-01

    We present the case of a 54-year-old man who developed progressive outer retinal necrosis (PORN) as an initial manifestation of HIV infection without any significant risk factors for infection with HIV. PORN is usually found as a manifestation of known AIDS late in the disease. Our patient presented with transient visual loss followed by decrease in visual acuity and facial rash. Subsequent investigation revealed anterior chamber tap positive for varicella zoster virus (VZV), as well as HIV positivity, with an initial CD4 count of 48 cells/µL. Systemic and intravitreal antivirals against VZV, and highly active antiretroviral therapy against HIV were started, which halted further progression of retinal necrosis. This case highlights the importance of suspecting PORN where there is a rapidly progressive retinitis, and also testing the patient for HIV, so appropriate treatment can be started. PMID:25948844

  2. Progressive outer retinal necrosis: manifestation of human immunodeficiency virus infection.

    PubMed

    Lo, Phey Feng; Lim, Rongxuan; Antonakis, Serafeim N; Almeida, Goncalo C

    2015-05-06

    We present the case of a 54-year-old man who developed progressive outer retinal necrosis (PORN) as an initial manifestation of HIV infection without any significant risk factors for infection with HIV. PORN is usually found as a manifestation of known AIDS late in the disease. Our patient presented with transient visual loss followed by decrease in visual acuity and facial rash. Subsequent investigation revealed anterior chamber tap positive for varicella zoster virus (VZV), as well as HIV positivity, with an initial CD4 count of 48 cells/µL. Systemic and intravitreal antivirals against VZV, and highly active antiretroviral therapy against HIV were started, which halted further progression of retinal necrosis. This case highlights the importance of suspecting PORN where there is a rapidly progressive retinitis, and also testing the patient for HIV, so appropriate treatment can be started.

  3. Human immunodeficiency virus and the central nervous system.

    PubMed

    Spencer, D C; Price, R W

    1992-01-01

    Neurological disease frequently complicates HIV-1 infection. In addition to opportunistic infections, a syndrome of combined cognitive and motor impairment, referred to as the AIDS dementia complex, has been recognized. While presumed to relate to HIV-1 itself, the pathogenesis of this syndrome remains uncertain. Because of the limited extent of productive brain HIV-1 infection in many cases, and because such infection involves macrophages and microglia rather than cells of neuroectodermal origin, current speculation centers on indirect mechanisms of brain injury including virus- or cell-coded neurotoxins. We review clinical and laboratory studies and also describe models of the interaction of HIV-1 and immune responses that might account for brain injury. PMID:1444270

  4. Immunobiology of the human immunodeficiency virus envelope and its relationship to vaccine strategies.

    PubMed

    Bolognesi, D P

    1990-02-01

    The envelope of human immunodeficiency virus (HIV) is an essential building block of the virus and it plays a major role in its life-cycle, particularly during the early stages of infection. It very likely determines, at least in part, the host range and tissue specificity of HIV, participates in pathogenic processes mediated by the virus and can itself be immunosuppressive. Because of its strategic location on the outer surface of the virion and the infected cell, it also represents an optimal (although not the only) target for immune attack and thus a prime candidate for development of vaccine and therapeutic strategies. Efforts to better understand its structural, functional and antigenic properties will thus be well worthwhile. Some of its principal features are reviewed herein and its role in vaccine strategies is discussed. PMID:2182967

  5. Transmission of feline immunodeficiency virus in domestic cats via artificial insemination.

    PubMed Central

    Jordan, H L; Howard, J; Sellon, R K; Wildt, D E; Tompkins, W A; Kennedy-Stoskopf, S

    1996-01-01

    The objective of this study was to determine whether semen from male domestic cats infected with feline immunodeficiency virus (FIV) can transmit virus to females. Twelve inseminations were performed by an intrauterine laparoscopic technique with fresh or cryopreserved electroejaculates from asymptomatic males chronically infected with the NCSU1 strain of FIV. Of six inseminations performed with fresh semen, three resulted in infection of queens, as indicated by seroconversion, expression of FIV gag provirus in peripheral blood leukocytes, and reduced peripheral CD4+/CD8+ T-lymphocyte ratios. None of the six inseminates with thawed cryopreserved semen resulted in infection. Two infected queens and one uninfected queen became pregnant. Virus was not evident in the seven offspring. We conclude that FIV can be transmitted horizontally by artificial insemination with fresh semen. PMID:8892958

  6. Potent and Specific Inhibition of Human Immunodeficiency Virus Type 1 Replication by RNA Interference

    PubMed Central

    Coburn, Glen A.; Cullen, Bryan R.

    2002-01-01

    Synthetic small interfering RNAs (siRNAs) have been shown to induce the degradation of specific mRNA targets in human cells by inducing RNA interference (RNAi). Here, we demonstrate that siRNA duplexes targeted against the essential Tat and Rev regulatory proteins encoded by human immunodeficiency virus type 1 (HIV-1) can specifically block Tat and Rev expression and function. More importantly, we show that these same siRNAs can effectively inhibit HIV-1 gene expression and replication in cell cultures, including those of human T-cell lines and primary lymphocytes. These observations demonstrate that RNAi can effectively block virus replication in human cells and raise the possibility that RNAi could provide an important innate protective response, particularly against viruses that express double-stranded RNAs as part of their replication cycle. PMID:12186906

  7. Challenge of chimpanzees (Pan troglodytes) immunized with human immunodeficiency virus envelope glycoprotein gp120.

    PubMed Central

    Arthur, L O; Bess, J W; Waters, D J; Pyle, S W; Kelliher, J C; Nara, P L; Krohn, K; Robey, W G; Langlois, A J; Gallo, R C

    1989-01-01

    The human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome, infects humans and chimpanzees. To determine the efficacy of immunization for preventing infection, chimpanzees were immunized with gp120 purified from human T-cell lymphotrophic virus type IIIB (HTLV-IIIB)-infected cell membranes and challenged with the homologous virus, HTLV-IIIB. A challenge stock of HTLV-IIIB was prepared by using unconcentrated HTLV-IIIB produced in H9 cells. The titer of the virus from this stock on human and chimpanzee peripheral blood mononuclear cells and in human lymphoid cell lines was determined; a cell culture infectivity of 10(4) was assigned. All chimpanzees inoculated intravenously with 40 cell culture infectious units or more became infected, as demonstrated by virus isolation and seroconversion. One of two chimpanzees inoculated with 4 cell culture infectious units became infected. Chimpanzees immunized with gp120 formulated in alum developed antibodies which precipitated gp120 and neutralized HTLV-IIIB. Peripheral blood mononuclear cells from gp120-vaccinated and HIV-infected animals showed a significantly greater response in proliferation assays with HIV proteins than did peripheral blood mononuclear cells from nonvaccinated and non-HIV-infected chimpanzees. Two of the gp120-alum-immunized chimpanzees were challenged with virus from the HTLV-IIIB stock. One animal received 400 cell culture infectious units, and one received 40 infectious units. Both animals became infected with HIV, indicating that the immune response elicited by immunization with gp120 formulated in alum was not effective in preventing infection with HIV-1. PMID:2555541

  8. Kaempferol acetylrhamnosides from the rhizome of Dryopteris crassirhizoma and their inhibitory effects on three different activities of human immunodeficiency virus-1 reverse transcriptase.

    PubMed

    Min, B S; Tomiyama, M; Ma, C M; Nakamura, N; Hattori, M

    2001-05-01

    Three new kaempferol glycosides, called crassirhizomosides A (1), B (2) and C (3), were isolated from the rhizome of Dryopteris crassirhizoma (Aspidiaceae), together with the known kaempferol glycoside, sutchuenoside A (4). The structures of 1-3 were determined as kaempferol 3-alpha-L-(2,4-di-O-acetyl)rhamnopyranoside-7-alpha-L-rhamnopyranoside, kaempferol 3-alpha-L-(3,4-di-O-acetyl)rhamnopyranoside, and kaempferol 3-alpha-L-(2,3-di-O-acetyl)rhamnopyranosside-7-alpha-L-rhamnopyranoside, respectively, by chemical and spectroscopic means. Inhibitory effects of 1-4 and kaempferol on human immunodeficiency virus reverse transcriptase-associated DNA polymerase (RNA-dependent DNA polymerase and DNA-dependent DNA polymerase) and RNase H activities were investigated.

  9. Structural Organization of DNA in Chlorella Viruses

    PubMed Central

    Wulfmeyer, Timo; Polzer, Christian; Hiepler, Gregor; Hamacher, Kay; Shoeman, Robert; Dunigan, David D.; Van Etten, James L.; Lolicato, Marco; Moroni, Anna; Thiel, Gerhard; Meckel, Tobias

    2012-01-01

    Chlorella viruses have icosahedral capsids with an internal membrane enclosing their large dsDNA genomes and associated proteins. Their genomes are packaged in the particles with a predicted DNA density of ca. 0.2 bp nm−3. Occasionally infection of an algal cell by an individual particle fails and the viral DNA is dynamically ejected from the capsid. This shows that the release of the DNA generates a force, which can aid in the transfer of the genome into the host in a successful infection. Imaging of ejected viral DNA indicates that it is intimately associated with proteins in a periodic fashion. The bulk of the protein particles detected by atomic force microscopy have a size of ∼60 kDa and two proteins (A278L and A282L) of about this size are among 6 basic putative DNA binding proteins found in a proteomic analysis of DNA binding proteins packaged in the virion. A combination of fluorescence images of ejected DNA and a bioinformatics analysis of the DNA reveal periodic patterns in the viral DNA. The periodic distribution of GC rich regions in the genome provides potential binding sites for basic proteins. This DNA/protein aggregation could be responsible for the periodic concentration of fluorescently labeled DNA observed in ejected viral DNA. Collectively the data indicate that the large chlorella viruses have a DNA packaging strategy that differs from bacteriophages; it involves proteins and share similarities to that of chromatin structure in eukaryotes. PMID:22359540

  10. Use of dried blood spot specimens in the detection of human immunodeficiency virus type 1 by the polymerase chain reaction.

    PubMed Central

    Cassol, S; Salas, T; Arella, M; Neumann, P; Schechter, M T; O'Shaughnessy, M

    1991-01-01

    Dried blood spots (DBSs) constitute a potentially valuable source of material for human immunodeficiency virus (HIV) serologic and molecular testing. To facilitate molecular testing, we have adapted the polymerase chain reaction (PCR) to the detection of HIV proviral DNA in DBS samples. The method is highly reproducible, with 75 microliters of whole dried blood providing sufficient DNA for duplicate testing with three primer sets. By using DBS PCR, 66 of 69 (95.6%) seropositive at-risk individuals tested positive by at least two primer sets and 85 of 85 (100%) low-risk seronegative blood donors tested negative by all three sets of primers. The frequency of HIV DNA detection in seronegative at-risk individuals was low, with only 1 of 58 (1.7%) individuals testing positive. These results show that in a clinical environment, HIV PCR analysis of DBS specimens is specific and sensitive. The method is cost effective and presents a useful alternative to the isolation of HIV from seropositive babies with an undefined infection status. Images PMID:1890166

  11. Monoclonal antibodies against human immunodeficiency virus type 1 integrase: epitope mapping and differential effects on integrase activities in vitro.

    PubMed Central

    Nilsen, B M; Haugan, I R; Berg, K; Olsen, L; Brown, P O; Helland, D E

    1996-01-01

    Human immunodeficiency virus type 1 (HIV-1) integrase (IN) catalyzes the integration of viral DNA into the host chromosome, an essential step in retroviral replication. As a tool to study the structure and function of this enzyme, monoclonal antibodies (MAbs) against HIV-1 IN were produced. Epitope mapping demonstrated that the 17 MAbs obtained could be divided into seven different groups, and the selection of MAbs representing these groups were tested for their effect on in vitro activities of IN. Four groups of MAbs recognized epitopes within the region of amino acids (aa) 1 to 16, 17 to 38, or 42 to 55 in and around the conserved HHCC motif near the N terminus of IN. MAbs binding to these epitopes inhibited end processing and DNA joining and either stimulated or had little effect on disintegration and reintegration activities of IN. Two MAbs binding to epitopes within the region of aa 56 to 102 in the central core or aa 186 to 250 in the C-terminal half of the protein showed only minor effects on the in vitro activities of IN. Three Mabs which recognized on epitope within the region of aa262 to 271 of HIV-1 IN cross-reacted with HIV-2 IN. MAbs binding to this epitope clearly inhibited end processing and DNA joining and stimulated or had little effect on disintegration. In contrast to the N-terminal-specific MAbs, these C-terminal-specific MAbs abolished reintegration activity of IN. PMID:8627677

  12. Human APOBEC3 Induced Mutation of Human Immunodeficiency Virus Type-1 Contributes to Adaptation and Evolution in Natural Infection

    PubMed Central

    Kim, Eun-Young; Lorenzo-Redondo, Ramon; Little, Susan J.; Chung, Yoon-Seok; Phalora, Prabhjeet K.; Maljkovic Berry, Irina; Archer, John; Penugonda, Sudhir; Fischer, Will; Richman, Douglas D.; Bhattacharya, Tanmoy; Malim, Michael H.; Wolinsky, Steven M.

    2014-01-01

    Human APOBEC3 proteins are cytidine deaminases that contribute broadly to innate immunity through the control of exogenous retrovirus replication and endogenous retroelement retrotransposition. As an intrinsic antiretroviral defense mechanism, APOBEC3 proteins induce extensive guanosine-to-adenosine (G-to-A) mutagenesis and inhibit synthesis of nascent human immunodeficiency virus-type 1 (HIV-1) cDNA. Human APOBEC3 proteins have additionally been proposed to induce infrequent, potentially non-lethal G-to-A mutations that make subtle contributions to sequence diversification of the viral genome and adaptation though acquisition of beneficial mutations. Using single-cycle HIV-1 infections in culture and highly parallel DNA sequencing, we defined trinucleotide contexts of the edited sites for APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H. We then compared these APOBEC3 editing contexts with the patterns of G-to-A mutations in HIV-1 DNA in cells obtained sequentially from ten patients with primary HIV-1 infection. Viral substitutions were highest in the preferred trinucleotide contexts of the edited sites for the APOBEC3 deaminases. Consistent with the effects of immune selection, amino acid changes accumulated at the APOBEC3 editing contexts located within human leukocyte antigen (HLA)-appropriate epitopes that are known or predicted to enable peptide binding. Thus, APOBEC3 activity may induce mutations that influence the genetic diversity and adaptation of the HIV-1 population in natural infection. PMID:25080100

  13. Identification of conserved amino acid residues critical for human immunodeficiency virus type 1 integrase function in vitro.

    PubMed Central

    Engelman, A; Craigie, R

    1992-01-01

    We have probed the structural organization of the human immunodeficiency virus type 1 integrase protein by limited proteolysis and the functional organization by site-directed mutagenesis of selected amino acid residues. A central region of the protein was relatively resistant to proteolysis. Proteins with altered amino acids in this region, or in the N-terminal part of the protein that includes a putative zinc-binding motif, were purified and assayed for 3' processing, DNA strand transfer, and disintegration activities in vitro. In general, these mutations had parallel effects on 3' processing and DNA strand transfer, suggesting that integrase may utilize a single active site for both reactions. The only proteins that were completely inactive in all three assays contained mutations at conserved amino acids in the central region, suggesting that this part of the protein may be involved in catalysis. In contrast, none of the mutations in the N-terminal region resulted in a protein that was inactive in all three assays, suggesting that this part of integrase may not be essential for catalysis. The disintegration reaction was particularly insensitive to these amino acid substitutions, indicating that some function that is important for 3' processing and DNA strand transfer may be dispensable for disintegration. Images PMID:1404595

  14. Mechanisms of androgen deficiency in human immunodeficiency virus-infected women with the wasting syndrome.

    PubMed

    Grinspoon, S; Corcoran, C; Stanley, T; Rabe, J; Wilkie, S

    2001-09-01

    Although prior studies suggest reduced androgen levels in women with acquired immune deficiency syndrome wasting, little is known regarding the regulation of adrenal and ovarian androgen secretion in such patients. We investigated ovarian and adrenal function in 13 human immunodeficiency virus-infected women with acquired immune deficiency syndrome wasting and 21 age- and body mass index-matched healthy control subjects studied in the early follicular phase. Subjects received hCG (5000 U, im) on d 1 and Cosyntropin (0.25 mg, i.v.) on d 3 after dexamethasone (1 mg, orally, at 2400 h) pretreatment on d 2. At baseline, human immunodeficiency virus-infected subjects demonstrated significantly reduced T [18 +/- 2 vs. 25 +/- 2 ng/dl (0.6 +/- 0.1 vs. 0.9 +/- 0.1 nmol/liter); P = 0.02], free T [1.5 +/- 0.1 vs. 2.4 +/- 0.2 pg/ml (5.3 +/- 0.5 vs. 8.3 +/- 0.6 pmol/liter); P = 0.001], androstenedione [119 +/- 6 vs. 162 +/- 14 ng/dl (4.16 +/- 0.20 vs. 5.66 +/- 0.48 nmol/liter); P = 0.02], and dehydroepiandrosterone sulfate [0.96 +/- 0.17 vs. 1.55 +/- 0.19 microg/ml (2.6 +/- 0.5 vs. 4.2 +/- 0.5 micromol/liter); P = 0.047] levels compared with the control subjects. T [8 +/- 2 vs. 6 +/- 2 ng/dl (0.3 +/- 0.1 vs. 0.2 +/- 0.1 nmol/liter); P = 0.48], free T [0.5 +/- 0.2 vs. 0.4 +/- 0.1 pg/ml (1.7 +/- 0.7 vs. 1.5 +/- 0.5 pmol/liter); P = 0.85], 17 hydroxyprogesterone [0.5 +/- 0.2 vs. 0.7 +/- 0.2 microg/liter (1.6 +/- 0.6 vs. 2.0 +/- 0.6 nmol/liter); P = 0.63], and androstenedione [-1 +/- 12 vs. 8 +/- 11 ng/dl (-0.03 +/- 0.42 vs. 0.28 +/- 0.39 nmol/liter), P = 0.61] responses to hCG were not different between the groups. Cortisol responses were increased and dehydroepiandrosterone sulfate responses were decreased in the human immunodeficiency virus-infected vs. control subjects after ACTH stimulation. The ratio of DHEA to cortisol was significantly decreased at 60 (71 +/- 11 vs. 107 +/- 10; P = 0.02) and 90 (63 +/- 8 vs. 102 +/- 9; P = 0.004) min post-ACTH in the human immunodeficiency

  15. Progressive immune dysfunction in cats experimentally infected with feline immunodeficiency virus.

    PubMed Central

    Torten, M; Franchini, M; Barlough, J E; George, J W; Mozes, E; Lutz, H; Pedersen, N C

    1991-01-01

    Within 6 months of infection with the Petaluma isolate of feline immunodeficiency virus, specific-pathogen-free domestic cats exhibited a decrease in the percentage and number of circulating CD4+ lymphocytes and in the CD4+/CD8+ T-cell ratio, along with a marginally significant depression of pokeweed mitogen-induced lymphocyte proliferation in vitro. There was no loss of responsiveness to concanavalin A during this stage, and the cats were capable of mounting a satisfactory antibody response to a T-dependent, synthetic polypeptide immunogen. The pokeweed mitogen response deficit became clearly demonstrable by 11 to 12 months postinfection. A decline in the lymphocyte proliferative response to concanavalin A and a diminished ability to mount an in vivo antibody response to the T-dependent immunogen evolved by 25 to 44 months postinfection. Virus infection did not affect the ability of cats to mount an antibody response to a T-independent synthetic polypeptide immunogen. These data indicate that feline immunodeficiency virus produces a slowly progressive deterioration of T-cell function but does not affect the ability of B cells to recognize and respond to a T-independent antigenic stimulus. PMID:1673159

  16. Persistent Peripheral Nervous System Damage in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy.

    PubMed

    Dorsey, Jamie L; Mangus, Lisa M; Hauer, Peter; Ebenezer, Gigi J; Queen, Suzanne E; Laast, Victoria A; Adams, Robert J; Mankowski, Joseph L

    2015-11-01

    Human immunodeficiency virus (HIV)-induced peripheral neuropathy is the most common neurologic complication associated with HIV infection. In addition to virus-mediated injury of the peripheral nervous system (PNS), treatment of HIV infection with combination antiretroviral therapy (cART) may induce toxic neuropathy as a side effect. Antiretroviral toxic neuropathy is clinically indistinguishable from the sensory neuropathy induced by HIV; in some patients, these 2 processes are likely superimposed. To study these intercurrent PNS disease processes, we first established a simian immunodeficiency virus (SIV)/pigtailed macaque model in which more than 90% of animals developed PNS changes closely resembling those seen in HIV-infected individuals with distal sensory neuropathy. To determine whether cART alters the progression of SIV-induced PNS damage, dorsal root ganglia and epidermal nerve fibers were evaluated in SIV-infected macaques after long-term suppressive cART. Although cART effectively suppressed SIV replication and reduced macrophage activation in the dorsal root ganglia, PGP 9.5 immunostaining and measurements of epidermal nerve fibers in the plantar surface of the feet of treated SIV-infected macaques clearly showed that cART did not normalize epidermal nerve fiber density. These findings illustrate that significant PNS damage persists in SIV-infected macaques on suppressive cART.

  17. Identification of human immunodeficiency virus type 1 envelope genes recombinant between subtypes B and F in two epidemiologically linked individuals from Brazil.

    PubMed Central

    Sabino, E C; Shpaer, E G; Morgado, M G; Korber, B T; Diaz, R S; Bongertz, V; Cavalcante, S; Galvão-Castro, B; Mullins, J I; Mayer, A

    1994-01-01

    Sequence analysis of a human immunodeficiency virus type 1 env gene PCR amplified from a Brazilian woman's peripheral blood mononuclear cell DNA (sample RJIO1) showed that it was likely to have been derived from a double recombination event between human immunodeficiency virus type 1 subtypes B and F. The major portion of the gp120 coding sequence belonged to the B lineage, but a segment of the C2 to V3 region (approximately 135 nucleotides) clearly associated with sequences of the F lineage. The subtype F-like segment had 15 noncontiguous signature nucleotides in common with Brazilian subtype F sequences that were not found, or were rare, in subtype B sequences. In contrast, this same segment had only 3 signature nucleotides shared with subtype B sequences and not present in the Brazilian subtype F sequences. Phylogenetic analysis, amino acid signature pattern analysis, and the pattern of synonymous mutations all supported the hypothesis of a recombinational origin of the RJIO1 sequence. Related recombinant genes were also detected in peripheral blood mononuclear cell DNA obtained from the woman's recent sexual partner, indicating that the recombination event probably occurred at some previous time in the chain of virus transmission. Divergent viral sequences in the V3 region were found in the male sexual partner, while a relatively homogeneous viral population was detected in the woman, consistent with her recent infection. PMID:8083973

  18. Pol gene quasispecies of human immunodeficiency virus: mutations associated with drug resistance in virus from patients undergoing no drug therapy.

    PubMed Central

    Nájera, I; Holguín, A; Quiñones-Mateu, M E; Muñoz-Fernández, M A; Nájera, R; López-Galíndez, C; Domingo, E

    1995-01-01

    The nucleotide sequences of two pol gene regions (codons 41 to 108 and 181 to 219 of reverse transcriptase) of 60 human immunodeficiency virus type 1 genomes obtained directly from primary lymphocytes from infected individuals are reported. In addition, the mutant spectra of several quasispecies have been sampled by repetitive sequencing of molecular clones representing the same pol genomic regions. Average mutation frequencies ranged from 1.6 x 10(-2) to 3.4 x 10(-2) substitutions per nucleotide for independent samples (relative to their consensus nucleotide sequence) and from 3.6 x 10(-3) to 1.1 x 10(-2) substitutions per nucleotide for individual quasispecies distributions. Several mutations leading to amino acid substitutions related to loss of sensitivity to reverse transcriptase inhibitors have been identified in samples from patients not subjected to antiretroviral therapy. Mutation frequencies in the codons previously identified as involved in resistance to reverse transcriptase inhibitors were very similar to the average mutation frequencies in the pol region analyzed. Thus, the finding of mutations related to drug resistance (even in the absence of positive selection by the corresponding drugs) is the expected consequence of the statistical distribution of mutations along the pol gene. The presence of such critical amino acid replacements in human immunodeficiency virus type 1 populations underscores the importance of viral quasispecies as reservoirs of phenotypic virus variants and has a number of implications for AIDS control. PMID:7983713

  19. Seroprevalence of Toxoplasma gondii and concurrent bartonella spp., feline immunodeficiency virus, and feline leukemia infections in cats from Grenada, West Indies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Toxoplasma gondii and Bartonella spp. are zoonotic pathogens of cats. Feline Immunodeficiency Virus (FIV), and Feline Leukemia Virus (FeLv) are related to Human Iimmunodeficiency Virus, and Human Leukemia Virus, respectively, and these viruses are immunosuppressive. In the present study, the prevale...

  20. Resource Manual for Handling Body Fluids in the School Setting To Prevent the Transmission of Human Immunodeficiency Virus and Hepatitis B Virus.

    ERIC Educational Resources Information Center

    Maryland State Dept. of Health and Mental Hygiene, Baltimore.

    Guidelines to prevent the transmission of blood-borne diseases, especially those caused by the Human Immunodeficiency Virus (HIV) and the Hepatitis B Virus (HBV), in the school setting are provided in this resource manual for school staff. Sections include information on the reasons for the development of this manual; a summary of the means of HIV…

  1. Serological survey of Toxoplasma gondii, Dirofilaria immitis, Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) infections in pet cats in Bangkok and vicinities, Thailand

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The seroprevalence of Toxoplasma gondii, Dirofilaria immitis (heartworm), feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) infections was examined using serum or plasma samples from 746 pet cats collected between May and July 2009 from clinics and hospitals located in and around ...

  2. Resource Manual for Handling Body Fluids in the School Setting To Prevent Transmission of Human Immunodeficiency Virus and Hepatitis B Virus. Revised Edition.

    ERIC Educational Resources Information Center

    Maryland State Dept. of Health and Mental Hygiene, Baltimore.

    This Maryland resource manual provides local education agencies with guidelines on how to handle body fluids to prevent the transmission of diseases, especially Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV), in the school setting. The first section summarizes the reasons for development of the manual. The second section summarizes…

  3. Electrospun fibers for the prevention of human immunodeficiency virus

    NASA Astrophysics Data System (ADS)

    Ball, Cameron

    HIV/AIDS education, testing, and treatment have thus far failed to cease the pandemic spread of the HIV virus. HIV prevention is hindered by a lack of protective options beyond the ABC approach of abstinence, being faithful, and using condoms. One approach to address this inadequacy is to develop antiviral products for vaginal or rectal application that provide receptive partner-initiated protection against viral infection during sex. Such products, termed anti-HIV microbicides, can especially empower young women to take control over their sexual health. This work explored a new approach to anti-HIV microbicides: electrospun fibers for the delivery of small-molecule antiretroviral drugs. Electrospun microbicides are nonwoven fabrics made from polymer-based nanofibers. The wide array of polymers available for electrospinning allowed for the incorporation and release of chemically diverse agents. Since electrospun fibers have an extremely high surface area to volume ratio, they serve as excellent delivery systems for rapid drug delivery of both hydrophilic and hydrophobic agents. The flexibility in the design of electrospun fibers afforded by coaxial electrospinning further enabled the formulation of sustained-release microbicides. To demonstrate the power of electrospinning to deliver drugs over multiple timescales, composite microbicide fabrics were created to provide both rapid and sustained drug release from a single device. This work has produced alternative microbicide formulations, while establishing methods for the thorough characterization of these systems and solutions for the needs of people at risk of HIV infection. By addressing problems in both HIV prevention and drug delivery, this work has expanded our capacity to engineer elegant solutions to complex and pressing global health challenges.

  4. Unusually high seroprevalence of Borna disease virus in clade E human immunodeficiency virus type 1-infected patients with sexually transmitted diseases in Thailand.

    PubMed Central

    Auwanit, W; Ayuthaya, P I; Nakaya, T; Fujiwara, S; Kurata, T; Yamanishi, K; Ikuta, K

    1996-01-01

    The seroprevalence of Borna disease virus (BDV) in human immunodeficiency virus type 1-infected individuals in Thailand was examined by using recombinant BDV p24. A high (38 to 48%) rate of seroprevalence of BDV was observed in clade E-infected patients with sexually transmitted diseases, compared with those in clade E-infected prostitutes (8.3%), pregnant women (0%), clade B-infected intravenous-drug users (0%), and human immunodeficiency virus type 1-negative blood donors (1.9%). PMID:8877141

  5. Pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in the era of antiretroviral therapy

    PubMed Central

    Velásquez, Jorge N; Ledesma, Bibiana A; Nigro, Monica G; Vittar, Natalia; Rueda, Nestor; De Carolis, Luis; Figueiras, Olga; Carnevale, Silvana; Corti, Marcelo

    2016-01-01

    Toxoplasmosis is a severe opportunistic infection in patients infected with the human immunodeficiency virus (HIV). The lung is a major site of infection after the central nervous system. In this report we described two cases of pneumonia due to Toxoplasma gondii infection in HIV patients with antiretroviral therapy. Clinical and radiological abnormalities are not specific. Pulmonary toxoplasmosis should be considered in HIV-infected patients with late stage of HIV, CD4 count less than 100 cells/µl and a poor adherence to HAART. PMID:26933317

  6. Pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in the era of antiretroviral therapy.

    PubMed

    Velásquez, Jorge N; Ledesma, Bibiana A; Nigro, Monica G; Vittar, Natalia; Rueda, Nestor; De Carolis, Luis; Figueiras, Olga; Carnevale, Silvana; Corti, Marcelo

    2016-01-01

    Toxoplasmosis is a severe opportunistic infection in patients infected with the human immunodeficiency virus (HIV). The lung is a major site of infection after the central nervous system. In this report we described two cases of pneumonia due to Toxoplasma gondii infection in HIV patients with antiretroviral therapy. Clinical and radiological abnormalities are not specific. Pulmonary toxoplasmosis should be considered in HIV-infected patients with late stage of HIV, CD4 count less than 100 cells/µl and a poor adherence to HAART.

  7. Differential human immunodeficiency virus expression in CD4+ cloned lymphocytes: from viral latency to replication.

    PubMed Central

    Chapel, A; Bensussan, A; Vilmer, E; Dormont, D

    1992-01-01

    By using cloning methodology, 13 CD4+, CD8-, CD45RO+, and CD29+ clones, isolated from human immunodeficiency virus (HIV)-negative donors, have been characterized and tested regarding their susceptibility to two strains of HIV type 1 (HIV-1). Infected clones possess integrated provirus. Only six are able to replicate HIV-1, while seven may normally grow without cytopathic effect and without viral replication. These results argue that all CD4+ lymphocyte clones may be infectable but that a heterogeneity exists regarding their abilities to replicate HIV-1. Images PMID:1374814

  8. Differential human immunodeficiency virus expression in CD4+ cloned lymphocytes: from viral latency to replication.

    PubMed

    Chapel, A; Bensussan, A; Vilmer, E; Dormont, D

    1992-06-01

    By using cloning methodology, 13 CD4+, CD8-, CD45RO+, and CD29+ clones, isolated from human immunodeficiency virus (HIV)-negative donors, have been characterized and tested regarding their susceptibility to two strains of HIV type 1 (HIV-1). Infected clones possess integrated provirus. Only six are able to replicate HIV-1, while seven may normally grow without cytopathic effect and without viral replication. These results argue that all CD4+ lymphocyte clones may be infectable but that a heterogeneity exists regarding their abilities to replicate HIV-1.

  9. Vulvar carcinoma in a 12-year-old girl with vertically acquired human immunodeficiency virus infection.

    PubMed

    Giaquinto, C; Del Mistro, A; De Rossi, A; Bertorelle, R; Giacomet, V; Ruga, E; Minucci, D

    2000-10-01

    We report the first case of a girl with vertically acquired human immunodeficiency virus (HIV) infection, who developed invasive squamous cell carcinoma of the vulva at 12 years of age. Lesions resembling bowenoid papulosis covered the perianal area as well. She underwent a nonmutilating surgical excision of the infiltrating lesion. More than 3 years later, her clinical condition is excellent, although dysplastic, noninfiltrating multifocal lesions persist. This case highlights the need to perform careful periodic genital examinations in all HIV-infected children and adolescents born to HIV-positive mothers.

  10. Counseling patients seropositive for human immunodeficiency virus. An approach for medical practice.

    PubMed Central

    Coates, T. J.; Lo, B.

    1990-01-01

    Persons at risk for infection with the human immunodeficiency virus are being encouraged to learn their serostatus. While such knowledge can help patients seek appropriate medical care, it can also be distressing. We describe an approach, based on crisis counseling, for physicians to use in working with patients infected with HIV. It can help physicians in assisting patients with emotional reactions to the diagnosis as well as in directing patients to manage practical issues of concern. Methods for discussing safer sex or injection practices are also presented. PMID:2293468

  11. Site-directed ELISA identifies a highly antigenic region of the simian immunodeficiency virus transmembrane glycoprotein.

    PubMed

    Johnson, P R; Parks, D E; Norrby, E; Lerner, R A; Purcell, R H; Chanock, R M

    1988-06-01

    The transmembrane glycoprotein (gp32) of the simian immunodeficiency virus (SIV) contains a highly antigenic region that includes amino acid residues 606-628. A synthetic peptide representing this region was highly immunoreactive with sera from SIV-infected primates in a site-directed enzyme-linked immunosorbent assay (ELISA). This reactivity extended across four primate species from three genera and identified infection with at least two distinct isolates of SIV. This site-directed ELISA represents a simple, accessible method with broad specificity for screening large numbers of primates for antibodies against SIV.

  12. Medication adherence feedback intervention predicts improved human immunodeficiency virus clinical markers.

    PubMed

    Reich, Warren A

    2013-12-01

    Thirty-three participants in a human immunodeficiency virus (HIV) medication adherence feedback (MAF) intervention were compared with 58 HIV-positive non-participants in laboratory-tested CD4 and viral load. The intervention provided adherence feedback and counselling based on a visual display from an electronic pill bottle (MEMS(TM) ). Multiple regression controlling for baseline CD4 and showed that postintervention CD4 was higher for MAF participants than for non-MAF participants. Non-MAF participants' CD4 significantly declined over time. MAF participants were also less likely than non-MAF participants to have a detectable postintervention viral load.

  13. Neurobehavioral Manifestations of Human Immunodeficiency Virus/AIDS: Diagnosis and Treatment.

    PubMed

    Singer, Elyse J; Thames, April D

    2016-02-01

    Behavioral disorders are common in persons infected with human immunodeficiency virus (HIV). The differential includes preexisting psychiatric diseases, substance abuse, direct effects of HIV infection, opportunistic infection, and the adverse effects of medical therapies. Many patients have more than one contributing or comorbid problem to explain these behavioral changes. The differential should always include consideration of psychosocial, genetic, and medical causes of disease. Treatment strategies must take into account the coadministration of antiretroviral therapy and the specific neurologic problems common in patients infected with HIV. PMID:26613994

  14. Orphans and Vulnerable Children Affected by Human Immunodeficiency Virus in Sub-Saharan Africa.

    PubMed

    Bryant, Malcolm; Beard, Jennifer

    2016-02-01

    In Sub-Saharan Africa, 15.1 million children have been orphaned because of human immunodeficiency virus (HIV). They face significant vulnerabilities, including stigma and discrimination, trauma and stress, illness, food insecurity, poverty, and difficulty accessing education. Millions of additional children who have living parents are vulnerable because their parents or other relatives are infected. This article reviews the current situation of orphans and vulnerable children, explores the underlying determinants of vulnerability and resilience, describes the response by the global community, and highlights the challenges as the HIV pandemic progresses through its fourth decade.

  15. Mechanism of selective inhibition of human immunodeficiency virus by ingenol triacetate.

    PubMed Central

    Fujiwara, M; Ijichi, K; Tokuhisa, K; Katsuura, K; Shigeta, S; Konno, K; Wang, G Y; Uemura, D; Yokota, T; Baba, M

    1996-01-01

    Ingenol 3,5,20-triacetate (ITA), one of the ingenol derivatives, is a selective inhibitor of human immunodeficiency virus (HIV) replication in vitro. ITA inhibited the replication of HIV strains in MT-4 cells at concentrations of 0.051 to 0.65 microM. This concentration was approximately 10(3)-fold lower than its cytotoxic threshold. The mechanism of action of ITA is primarily attributed to the inhibition of viral adsorption to the host cells, but it is distinct from the mechanism of inhibition by other adsorption inhibitors. PMID:8787923

  16. One approach to care for patients infected with human immunodeficiency virus in an academic medical center.

    PubMed Central

    Jacobs, J. L.; Damson, L. C.; Rogers, D. E.

    1996-01-01

    The human immunodeficiency virus (HIV) epidemic poses unprecedented challenges to the health-care system. Caregivers must contend both with the complicated clinical syndromes associated with HIV infection and with issues that are central to the epidemic, such as discrimination, isolation, poverty, and substance abuse. Our HIV treatment program combines and enhances the resources of an academic medical center in a multidisciplinary care model. All patients, regardless of payor class, are offered services from 10 different disciplines. The same team of clinicians follows patients in the clinic and hospital. The program is flexible, non-hierarchical, and open to community participation. This approach may be a useful model for other institutions. PMID:8982523

  17. Twenty years of human immunodeficiency virus care at the Mayo Clinic: Past, present and future

    PubMed Central

    Cummins, Nathan W; Badley, Andrew D; Kasten, Mary J; Sampath, Rahul; Temesgen, Zelalem; Whitaker, Jennifer A; Wilson, John W; Yao, Joseph D; Zeuli, John; Rizza, Stacey A

    2016-01-01

    The Mayo human immunodeficiency virus (HIV) Clinic has been providing patient centered care for persons living with HIV in Minnesota and beyond for the past 20 years. Through multidisciplinary engagement, vital clinical outcomes such as retention in care, initiation of antiretroviral therapy and virologic suppression are maximized. In this commentary, we describe the history of the Mayo HIV Clinic and its best practices, providing a “Mayo Model” of HIV care that exceeds national outcomes and may be applicable in other settings. PMID:27175350

  18. Bubble continuous positive airway pressure in a human immunodeficiency virus-infected infant

    PubMed Central

    McCollum, E. D.; Smith, A.; Golitko, C. L.

    2014-01-01

    SUMMARY World Health Organization-classified very severe pneumonia due to Pneumocystis jirovecii infection is recognized as a life-threatening condition in human immunodeficiency virus (HIV) infected infants. We recount the use of nasal bubble continuous positive airway pressure (BCPAP) in an HIV-infected African infant with very severe pneumonia and treatment failure due to suspected infection with P. jirovecii. We also examine the potential implications of BCPAP use in resource-poor settings with a high case index of acute respiratory failure due to HIV-related pneumonia, but limited access to mechanical ventilation. PMID:21396221

  19. Proteins, peptides, polysaccharides, and nucleotides with inhibitory activity on human immunodeficiency virus and its enzymes.

    PubMed

    Ng, Tzi Bun; Cheung, Randy Chi Fai; Wong, Jack Ho; Chan, Wai Yee

    2015-12-01

    Human immunodeficiency virus (HIV), the causative agent of acquired immune deficiency syndrome, has claimed innumerable lives in the past. Many biomolecules which suppress HIV replication and also other biomolecules that inhibit enzymes essential to HIV replication have been reported. Proteins including a variety of milk proteins, ribosome-inactivating proteins, ribonucleases, antifungal proteins, and trypsin inhibitors; peptides comprising cathelicidins, defensins, synthetic peptides, and others; polysaccharides and polysaccharopeptides; nucleosides, nucleotides, and ribozymes, demonstrated anti-HIV activity. In many cases, the mechanism of anti-HIV action has been elucidated. Strategies have been devised to augment the anti-HIV potency of these compounds.

  20. Action of uracil analogs on human immunodeficiency virus type 1 and its reverse transcriptase.

    PubMed Central

    Piras, G; Dutschman, G E; Im, G J; Pan, B C; Chu, S H; Cheng, Y C

    1995-01-01

    Three structural analogs of 5-ethyl-1-benzyloxymethyl-6-(phenylthio)uracil (E-BPU) inhibited human immunodeficiency virus type 1 (HIV-1) replication without cytotoxicity in vitro and were more potent than azidothymidine and were as potent as E-BPU. The target of these compounds is HIV-1 reverse transcriptase. Reverse transcriptases resistant to nevirapine (tyrosine at position 181 to cysteine) and TIBO R82150 (leucine at position 100 to isoleucine) are cross resistant to E-BPU analogs. Nevirapine- or TIBO R82150-resistant HIV-1 were cross resistant to E-BPU analogs but were inhibited at concentrations 11- to 135-fold lower than the cytotoxic doses. PMID:7537030

  1. Nodular Erythema Elevatum Diutinum Mimicking Kaposi's Sarcoma in a Human Immunodeficiency Virus Infected Patient

    PubMed Central

    Rao, G Raghurama; Joshi, Rajiv; Phaneendra Prasad, A Krishna; Amareswar, A; Sandhya, S; Sridevi, M

    2014-01-01

    Erythema elevatum diutinum (EED) has been emerging as a specific Human Immunodeficiency Virus (HIV) associated dermatosis in recent times. It is an extremely rare chronic disease of unknown origin and part of the spectrum of leukocytoclastic vasculitis. We describe a case of EED simulating Kaposi's sarcoma in a 52-year-old HIV infected female patient with no previous opportunistic infections and CD4+ count of 164/mm3. Therapy with oral dapsone (100 mg/day) for two weeks resulted in resolution of some lesions. PMID:25484391

  2. Diabetes mellitus type 2 and abnormal glucose metabolism in the setting of human immunodeficiency virus.

    PubMed

    Hadigan, Colleen; Kattakuzhy, Sarah

    2014-09-01

    As the modern era of combination antiretroviral therapy has increased life expectancy for individuals infected with the human immunodeficiency virus (HIV), type 2 diabetes mellitus and disorders of glucose metabolism have emerged as an important issue in the care of this population. Multiple mechanisms, both specific and nonspecific to HIV, underlie a significant prevalence. Although best-practice diagnostic testing remains unclear, the risks associated with diabetes in the setting of HIV are well characterized, ranging from organ-specific damage to socioeconomic decline. As population-specific treatment data are limited, current guidelines serve as a basis for ongoing management.

  3. Role of dendritic cells in immunopathogenesis of human immunodeficiency virus infection.

    PubMed Central

    Weissman, D; Fauci, A S

    1997-01-01

    The role of dendritic cells (DC) in the pathogenesis of human immunodeficiency virus (HIV) disease has been a subject of considerable interest for several years. Initial studies focused on the infection, dysfunction, and depletion of DC in HIV-infected individuals. More recent studies have begun to identify the functional role of DC in the initiation and propagation of viral replication in T cells in HIV-infected individuals. This review discusses recent data regarding the role of DC in HIV disease with the aim of delineating basic immunopathogenic principles of infection and the development of therapeutic strategies. PMID:9105759

  4. Testing women for human immunodeficiency virus infection: who, when, and how?

    PubMed

    Clark, Jill; Lampe, Margaret A; Jamieson, Denise J

    2008-09-01

    Obstetrician-gynecologists provide comprehensive primary and preventive care for women and are ideally suited to provide human immunodeficiency virus (HIV) screening for their patients. This paper provides a summary and rationale for the current recommendations for HIV testing among women in the United States, emphasizing recommendations from the Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists [corrected] Who should receive HIV testing, when and how often testing should be conducted, and how testing should be offered are discussed. These recommendations are described separately for general populations (including nonpregnant women) and for pregnant women and their infants.

  5. Pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in the era of antiretroviral therapy.

    PubMed

    Velásquez, Jorge N; Ledesma, Bibiana A; Nigro, Monica G; Vittar, Natalia; Rueda, Nestor; De Carolis, Luis; Figueiras, Olga; Carnevale, Silvana; Corti, Marcelo

    2016-01-01

    Toxoplasmosis is a severe opportunistic infection in patients infected with the human immunodeficiency virus (HIV). The lung is a major site of infection after the central nervous system. In this report we described two cases of pneumonia due to Toxoplasma gondii infection in HIV patients with antiretroviral therapy. Clinical and radiological abnormalities are not specific. Pulmonary toxoplasmosis should be considered in HIV-infected patients with late stage of HIV, CD4 count less than 100 cells/µl and a poor adherence to HAART. PMID:26933317

  6. Orphans and Vulnerable Children Affected by Human Immunodeficiency Virus in Sub-Saharan Africa.

    PubMed

    Bryant, Malcolm; Beard, Jennifer

    2016-02-01

    In Sub-Saharan Africa, 15.1 million children have been orphaned because of human immunodeficiency virus (HIV). They face significant vulnerabilities, including stigma and discrimination, trauma and stress, illness, food insecurity, poverty, and difficulty accessing education. Millions of additional children who have living parents are vulnerable because their parents or other relatives are infected. This article reviews the current situation of orphans and vulnerable children, explores the underlying determinants of vulnerability and resilience, describes the response by the global community, and highlights the challenges as the HIV pandemic progresses through its fourth decade. PMID:26613693

  7. Cardiovascular disease in human immunodeficiency virus infected patients: A true or perceived risk?

    PubMed Central

    Shahbaz, Shima; Manicardi, Marcella; Guaraldi, Giovanni; Raggi, Paolo

    2015-01-01

    After the successful introduction of highly active antiretroviral agents the survival of patients infected with the human immunodeficiency virus (HIV) in developed countries has increased substantially. This has allowed the surfacing of several chronic diseases among which cardiovascular disease (CVD) is prominent. The pathogenesis of CVD in HIV is complex and involves a combination of traditional and HIV related factors. An accurate assessment of risk of CVD in these patients is still elusive and as a consequence the most appropriate preventive and therapeutic interventions remain controversial. PMID:26516417

  8. Can antiretroviral therapy be used to prevent sexual transmission of human immunodeficiency virus type 1?

    PubMed

    Hosseinipour, Mina; Cohen, Myron S; Vernazza, Pietro L; Kashuba, Angela D M

    2002-05-15

    Approximately 5 million people annually are newly infected with human immunodeficiency virus (HIV). Although education, behavior modification, and promotion of condom use are effective transmission-prevention measures, the severity of the pandemic demands that all possible prevention strategies be explored. Antiretroviral therapy has the potential to decrease sexual transmission of HIV type 1 by reducing levels of HIV RNA and thus decreasing the risk that infected persons will transmit the disease or by its use as preexposure or postexposure prophylaxis. In this article, we explore the rationale for using antiretroviral therapy to prevent sexual transmission of HIV, as well as the limitations of this approach. PMID:11981736

  9. Ocelots on Barro Colorado Island Are Infected with Feline Immunodeficiency Virus but Not Other Common Feline and Canine Viruses

    PubMed Central

    Franklin, Samuel P.; Kays, Roland W.; Moreno, Ricardo; TerWee, Julie A.; Troyer, Jennifer L.; VandeWoude, Sue

    2011-01-01

    Transmission of pathogens from domestic animals to wildlife populations (spill-over) has precipitated local wildlife extinctions in multiple geographic locations. Identifying such events before they cause population declines requires differentiating spillover from endemic disease, a challenge complicated by a lack of baseline data from wildlife populations that are isolated from domestic animals. We tested sera collected from 12 ocelots (Leopardus pardalis) native to Barro Colorado Island, Panama, which is free of domestic animals, for antibodies to feline herpes virus, feline calicivirus, feline corona virus, feline panleukopenia virus, canine distemper virus, and feline immunodeficiency virus (FIV), typically a species-specific infection. Samples also were tested for feline leukemia virus antigens. Positive tests results were only observed for FIV; 50% of the ocelots were positive. We hypothesize that isolation of this population has prevented introduction of pathogens typically attributed to contact with domestic animals. The high density of ocelots on Barro Colorado Island may contribute to a high prevalence of FIV infection, as would be expected with increased contact rates among conspecifics in a geographically restricted population. PMID:18689668

  10. Plasmacytoid Dendritic Cell Infection and Sensing Capacity during Pathogenic and Nonpathogenic Simian Immunodeficiency Virus Infection

    PubMed Central

    Jochems, Simon P.; Jacquelin, Beatrice; Chauveau, Lise; Huot, Nicolas; Petitjean, Gaël; Lepelley, Alice; Liovat, Anne-Sophie; Ploquin, Mickaël J.; Cartwright, Emily K.; Bosinger, Steven E.; Silvestri, Guido; Barré-Sinoussi, Françoise; Lebon, Pierre; Schwartz, Olivier

    2015-01-01

    ABSTRACT Human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques (MAC) lead to chronic inflammation and AIDS. Natural hosts, such as African green monkeys (AGM) and sooty mangabeys (SM), are protected against SIV-induced chronic inflammation and AIDS. Here, we report that AGM plasmacytoid dendritic cells (pDC) express extremely low levels of CD4, unlike MAC and human pDC. Despite this, AGM pDC efficiently sensed SIVagm, but not heterologous HIV/SIV isolates, indicating a virus-host adaptation. Moreover, both AGM and SM pDC were found to be, in contrast to MAC pDC, predominantly negative for CCR5. Despite such limited CD4 and CCR5 expression, lymphoid tissue pDC were infected to a degree similar to that seen with CD4+ T cells in both MAC and AGM. Altogether, our finding of efficient pDC infection by SIV in vivo identifies pDC as a potential viral reservoir in lymphoid tissues. We discovered low expression of CD4 on AGM pDC, which did not preclude efficient sensing of host-adapted viruses. Therefore, pDC infection and efficient sensing are not prerequisites for chronic inflammation. The high level of pDC infection by SIVagm suggests that if CCR5 paucity on immune cells is important for nonpathogenesis of natural hosts, it is possibly not due to its role as a coreceptor. IMPORTANCE The ability of certain key immune cell subsets to resist infection might contribute to the asymptomatic nature of simian immunodeficiency virus (SIV) infection in its natural hosts, such as African green monkeys (AGM) and sooty mangabeys (SM). This relative resistance to infection has been correlated with reduced expression of CD4 and/or CCR5. We show that plasmacytoid dendritic cells (pDC) of natural hosts display reduced CD4 and/or CCR5 expression, unlike macaque pDC. Surprisingly, this did not protect AGM pDC, as infection levels were similar to those found in MAC pDC. Furthermore, we show that AGM pDC did not consistently produce type I

  11. Deciphering Human Immunodeficiency Virus Type 1 Transmission and Early Envelope Diversification by Single-Genome Amplification and Sequencing▿

    PubMed Central

    Salazar-Gonzalez, Jesus F.; Bailes, Elizabeth; Pham, Kimmy T.; Salazar, Maria G.; Guffey, M. Brad; Keele, Brandon F.; Derdeyn, Cynthia A.; Farmer, Paul; Hunter, Eric; Allen, Susan; Manigart, Olivier; Mulenga, Joseph; Anderson, Jeffrey A.; Swanstrom, Ronald; Haynes, Barton F.; Athreya, Gayathri S.; Korber, Bette T. M.; Sharp, Paul M.; Shaw, George M.; Hahn, Beatrice H.

    2008-01-01

    Accurate identification of the transmitted virus and sequences evolving from it could be instrumental in elucidating the transmission of human immunodeficiency virus type 1 (HIV-1) and in developing vaccines, drugs, or microbicides to prevent infection. Here we describe an experimental approach to analyze HIV-1 env genes as intact genetic units amplified from plasma virion RNA by single-genome amplification (SGA), followed by direct sequencing of uncloned DNA amplicons. We show that this strategy precludes in vitro artifacts caused by Taq-induced nucleotide substitutions and template switching, provides an accurate representation of the env quasispecies in vivo, and has an overall error rate (including nucleotide misincorporation, insertion, and deletion) of less than 8 × 10−5. Applying this method to the analysis of virus in plasma from 12 Zambian subjects from whom samples were obtained within 3 months of seroconversion, we show that transmitted or early founder viruses can be identified and that molecular pathways and rates of early env diversification can be defined. Specifically, we show that 8 of the 12 subjects were each infected by a single virus, while 4 others acquired more than one virus; that the rate of virus evolution in one subject during an 80-day period spanning seroconversion was 1.7 × 10−5 substitutions per site per day; and that evidence of strong immunologic selection can be seen in Env and overlapping Rev sequences based on nonrandom accumulation of nonsynonymous mutations. We also compared the results of the SGA approach with those of more-conventional bulk PCR amplification methods performed on the same patient samples and found that the latter is associated with excessive rates of Taq-induced recombination, nucleotide misincorporation, template resampling, and cloning bias. These findings indicate that HIV-1 env genes, other viral genes, and even full-length viral genomes responsible for productive clinical infection can be identified

  12. Preventing opportunistic infections in human immunodeficiency virus-infected persons: implications for the developing world.

    PubMed

    Kaplan, J E; Hu, D J; Holmes, K K; Jaffe, H W; Masur, H; De Cock, K M

    1996-07-01

    More than 18 million persons in the world are estimated to have been infected with human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome (AIDS). As immunodeficiency progresses, these persons become susceptible to a wide variety of opportunistic infections (OIs) The spectrum of OIs varies among regions of the world. Tuberculosis is the most common serious OI in sub-Saharan Africa and is also more common in Latin America and in Asia than in the United States. Bacterial and parasitic infections are prevalent in Africa; protozoal infections such as toxoplasmosis, cryptosporidiosis, and isosporiasis are also common in Latin America. Fungal infections, including cryptococcosis and Penicillium marneffei infection, appear to be prevalent in Southeast Asia. Despite limited health resources in these regions, some measures that are recommended to prevent OIs in the United States may be useful for prolonging and improving the quality of life of HIV-infected persons. These include trimethoprim-sulfamethoxazole to prevent Pneumocystis carinii pneumonia, toxoplasmosis, and bacterial infections; isoniazid to prevent tuberculosis; and 23-valent pneumococcal vaccine to prevent disease due to Streptococcus pneumoniae. Research is needed to determine the spectrum of OIs and the efficacy of various prevention measures in resource-poor nations, and health officials need to determine a minimum standard of care for HIV-infected persons. An increasing problem in the developing world, HIV/AIDS should receive attention comparable to other tropical diseases.

  13. Performance of an Early Infant Diagnostic Test, AmpliSens DNA-HIV-FRT, Using Dried Blood Spots Collected from Children Born to Human Immunodeficiency Virus-Infected Mothers in Ukraine

    PubMed Central

    Shanmugam, Vedapuri; Azarskova, Marianna; Nguyen, Shon; Hurlston, Mackenzie; Sabatier, Jennifer; Zhang, Guoqing; Osmanov, Saladin; Ellenberger, Dennis; Yang, Chunfu; Vitek, Charles; Liulchuk, Maria; Nizova, Natalya

    2015-01-01

    An accurate accessible test for early infant diagnosis (EID) is crucial for identifying HIV-infected infants and linking them to treatment. To improve EID services in Ukraine, dried blood spot (DBS) samples obtained from 237 HIV-exposed children (≤18 months of age) in six regions in Ukraine in 2012 to 2013 were tested with the AmpliSens DNA-HIV-FRT assay, the Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) HIV-1 Qual test, and the Abbott RealTime HIV-1 Qualitative assay. In comparison with the paired whole-blood results generated from AmpliSens testing at the oblast HIV reference laboratories in Ukraine, the sensitivity was 0.99 (95% confidence interval [CI], 0.95 to 1.00) for the AmpliSens and Roche CAP/CTM Qual assays and 0.96 (95% CI, 0.90 to 0.98) for the Abbott Qualitative assay. The specificity was 1.00 (95% CI, 0.97 to 1.00) for the AmpliSens and Abbott Qualitative assays and 0.99 (95% CI, 0.96 to 1.00) for the Roche CAP/CTM Qual assay. McNemar analysis indicated that the proportions of positive results for the tests were not significantly different (P > 0.05). Cohen's kappa (0.97 to 0.99) indicated almost perfect agreement among the three tests. These results indicated that the AmpliSens DBS and whole-blood tests performed equally well and were comparable to the two commercially available EID tests. More importantly, the performance characteristics of the AmpliSens DBS test meets the World Health Organization EID test requirements; implementing AmpliSens DBS testing might improve EID services in resource-limited settings. PMID:26447114

  14. Variable epitope libraries: new vaccine immunogens capable of inducing broad human immunodeficiency virus type 1-neutralizing antibody response.

    PubMed

    Charles-Niño, Claudia; Pedroza-Roldan, Cesar; Viveros, Monica; Gevorkian, Goar; Manoutcharian, Karen

    2011-07-18

    The extreme antigenic variability of human immunodeficiency virus (HIV) leads to immune escape of the virus, representing a major challenge in the design of effective vaccine. We have developed a novel concept for immunogen construction based on introduction of massive mutations within the epitopes targeting antigenically variable pathogens and diseases. Previously, we showed that these immunogens carrying large combinatorial libraries of mutated epitope variants, termed as variable epitope libraries (VELs), induce potent, broad and long lasting CD8+IFN-γ+ T-cell response. Moreover, we demonstrated that these T cells recognize more than 50% of heavily mutated variants (5 out of 10 amino acid positions were mutated in each epitope variant) of HIV-1 gp120 V3 loop-derived cytotoxic T lymphocyte epitope (RGPGRAFVTI) in mice. The constructed VELs had complexities of 10000 and 12500 individual members, generated as plasmid DNA or as M13 phage display combinatorial libraries, respectively, and with structural composition RGPGXAXXXX or XGXGXAXVXI, where X is any of 20 natural amino acids. Here, we demonstrated that sera from mice immunized with these VELs are capable of neutralizing 5 out of 10 viral isolates from Tier 2 reference panel of subtype B envelope clones, including HIV-1 isolates which are known to be resistant to neutralization by several potent monoclonal antibodies, described previously. These data indicate the feasibility of the application of immunogens based on VEL concept as an alternative approach for the development of molecular vaccines against antigenically variable pathogens.

  15. Oral Immunization with Recombinant Vaccinia Virus Prime and Intramuscular Protein Boost Provides Protection against Intrarectal Simian-Human Immunodeficiency Virus Challenge in Macaques

    PubMed Central

    Thippeshappa, Rajesh; Tian, Baoping; Cleveland, Brad; Guo, Wenjin; Polacino, Patricia

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) acquisition occurs predominantly through mucosal transmission. We hypothesized that greater mucosal immune responses and protective efficacy against mucosal HIV-1 infection may be achieved by prime-boost immunization at mucosal sites. We used a macaque model to determine the safety, immunogenicity, and protective efficacy of orally delivered, replication-competent but attenuated recombinant vaccinia viruses expressing full-length HIV-1 SF162 envelope (Env) or simian immunodeficiency virus (SIV) Gag-Pol proteins. We examined the dose and route that are suitable for oral immunization with recombinant vaccinia viruses. We showed that sublingual inoculation of two vaccinia virus-naive pigtailed macaques with 5 × 108 PFU of recombinant vaccinia viruses was safe. However, sublingual inoculation with a higher dose or tonsillar inoculation resulted in secondary oral lesions, indicating the need to optimize the dose and route for oral immunization with replication-competent vaccinia virus vectors. Oral priming alone elicited antibody responses to vaccinia virus and to the SF162 Env protein. Intramuscular immunization with the SF162 gp120 protein at either 20 or 21 weeks postpriming resulted in a significant boost in antibody responses in both systemic and mucosal compartments. Furthermore, we showed that immune responses induced by recombinant vaccinia virus priming and intramuscular protein boosting provided protection against intrarectal challenge with the simian-human immunodeficiency virus SHIV-SF162-P4. PMID:26718849

  16. Seroprevalence of the Hepatitis B, Hepatitis C, and Human Immunodeficiency Viruses and Treponema pallidum at the Beijing General Hospital from 2010 to 2014: A Cross-Sectional Study

    PubMed Central

    Xu, Shaoxia; Wang, Qiaofeng; Zhang, Weihong; Qiu, Zhifeng; Cui, Jingtao; Yan, Wenjuan; Ni, Anping

    2015-01-01

    Background The hepatitis B, hepatitis C, human immunodeficiency viruses and Treponema pallidum are important causes of infectious diseases concern to public health. Methods Between 2010 and 2014, we used an automated chemiluminescence microparticle immunoassay to detect the hepatitis B, hepatitis C, and human immunodeficiency viruses as well as Treponema pallidum (the rapid plasma regain test was used in 2010–2011). Positive human immunodeficiency virus tests were confirmed via western blotting. Results Among 416,130 subjects, the seroprevalences for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and Treponema pallidum were 5.72%, 1.23%, 0.196%, and 0.76%, respectively. Among 671 patients with positive human immunodeficiency virus results, 392 cases were confirmed via western blotting. Hepatitis B and human immunodeficiency virus infections were more frequent in men (7.78% and 0.26%, respectively) than in women (4.45% and 0.021%, respectively). The hepatitis B and C virus seroprevalences decreased from 6.21% and 1.58%, respectively, in 2010, to 5.37% and 0.988%, respectively, in 2014. The human immunodeficiency virus seroprevalence increased from 0.04% in 2010 to 0.17% in 2014, and was elevated in the Infectious Disease (2.65%), Emergency (1.71%), and Dermatology and Sexually Transmitted Diseases (1.12%) departments. The specificity of the human immunodeficiency virus screening was 71.4%. The false positive rates for the Treponema pallidum screening tests increased in patients who were 60–70 years old. The co-infection rates for the hepatitis C and human immunodeficiency viruses were 0.47% in hepatitis C virus-positive patients and 7.33% in human immunodeficiency virus-positive patients. Conclusions During 2010–2014, hepatitis B virus and human immunodeficiency virus infections were more frequent among men at our institution. Although the seroprevalences of hepatitis B and C viruses decreased, the seroprevalence of human immunodeficiency

  17. Mini review: current molecular methods for the detection and quantification of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus type 1.

    PubMed

    Albertoni, Guilherme; Castelo Girão, Manoel João Batista; Schor, Nestor

    2014-08-01

    The detection of acute human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection is vital for controlling the spread of HIV, HBV, and HCV to uninfected individuals. Considering that these viruses have high replication rates and are undetectable by serological markers, early detection upon transmission is crucial. Various nucleic acid assays have been developed for diagnostics and therapeutic monitoring of infections. In the past decade, rapid and sensitive molecular techniques such as PCR have revolutionized the detection of a variety of infectious viruses, including HIV, HCV, and HBV. Here, we describe two of the most commonly used licensed methods for the detection and quantification of HIV, HCV, and HBV: the cobas TaqScreen MPX (PCR) test and the Tigris System. We used transcription-mediated amplification to review and compare the development and efficiency of these technologies. PMID:24927665

  18. Identification of cis-acting repressive sequences within the negative regulatory element of human immunodeficiency virus type 1.

    PubMed Central

    Lu, Y C; Touzjian, N; Stenzel, M; Dorfman, T; Sodroski, J G; Haseltine, W A

    1990-01-01

    The negative regulatory element of human immunodeficiency virus type 1 is a 260-nucleotide-long sequence that decreases the rate of RNA transcription initiation specified by the long terminal repeat. This region has the potential to bind several cellular transcription factors. Here it is shown that sequences which recognize the NFAT-1 and USF cellular transcription factors contribute to this negative regulatory effect. The sequences within the negative regulatory element which resemble the AP-1 site and the URS do not negatively regulate human immunodeficiency virus long terminal repeat transcription initiation. PMID:2398545

  19. Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1

    PubMed Central

    Moore, Penny L.; Crooks, Emma T.; Porter, Lauren; Zhu, Ping; Cayanan, Charmagne S.; Grise, Henry; Corcoran, Paul; Zwick, Michael B.; Franti, Michael; Morris, Lynn; Roux, Kenneth H.; Burton, Dennis R.; Binley, James M.

    2006-01-01

    Human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies are thought be distinguished from nonneutralizing antibodies by their ability to recognize functional gp120/gp41 envelope glycoprotein (Env) trimers. The antibody responses induced by natural HIV-1 infection or by vaccine candidates tested to date consist largely of nonneutralizing antibodies. One might have expected a more vigorous neutralizing response, particularly against virus particles that bear functional trimers. The recent surprising observation that nonneutralizing antibodies can specifically capture HIV-1 may provide a clue relating to this paradox. Specifically, it was suggested that forms of Env, to which nonneutralizing antibodies can bind, exist on virus surfaces. Here, we present evidence that HIV-1 particles bear nonfunctional gp120/gp41 monomers and gp120-depleted gp41 stumps. Using a native electrophoresis band shift assay, we show that antibody-trimer binding predicts neutralization and that the nonfunctional forms of Env may account for virus capture by nonneutralizing antibodies. We hypothesize that these nonfunctional forms of Env on particle surfaces serve to divert the antibody response, helping the virus to evade neutralization. PMID:16474158

  20. Effective ex vivo neutralization of human immunodeficiency virus type 1 in plasma by recombinant immunoglobulin molecules.

    PubMed Central

    Gauduin, M C; Allaway, G P; Maddon, P J; Barbas, C F; Burton, D R; Koup, R A

    1996-01-01

    We tested the ability of human monoclonal antibodies (immunoglobulin G1b12 [IgG1b12] and 19b) and CD4-based molecules (CD4-IgG2 and soluble CD4 [sCD4]) to neutralize human immunodeficiency virus type 1 directly from the plasma of seropositive donors in an ex vivo neutralization assay. IgG1b12 and CD4-IgG2, at concentrations from 1 to 25 micrograms/ml, were found to be effective at reducing the HIV-1 titer in most plasma samples. When viruses recovered from plasma samples were expanded to produce virus stocks, no correlation between the neutralization sensitivities to IgG1b12 and CD4-IgG2 of the in vitro passaged stocks and those of the ex vivo neutralizations performed directly on the plasma was observed. These differences could be due to changes in neutralization sensitivity that occur after one passage of the virus in vitro, or they could be related to the presence of complement or antibodies in the plasma. Furthermore, differences in expression of adhesion molecules on plasma-derived and phytohemagglutinin-activated peripheral blood mononuclear cell-derived viruses could be involved. These studies suggest that IgG1b12 and CD4-IgG2 have broad and potent neutralizing activity in both in vitro and ex vivo neutralization assays and should be considered for use as potential immunoprophylactic or therapeutic agents. PMID:8642690

  1. Complex determinants of macrophage tropism in env of simian immunodeficiency virus.

    PubMed

    Mori, K; Ringler, D J; Kodama, T; Desrosiers, R C

    1992-04-01

    Macrophage-tropic virus variants evolved during the course of infection of individual rhesus monkeys with cloned, non-macrophagetropic simian immunodeficiency virus. Specific changes in the envelope gene (env) were found to be primarily responsible for the dramatic increase in the ability of the virus to replicate in macrophages. Cloned viruses differing at nine amino acid positions in env exhibited a more than 100-fold difference in replicative capacity for primary cultures of rhesus monkey alveolar macrophages. At least five of the nine amino acid changes contributed to macrophage tropism. These determinants were distributed across the full length of env, including both the gp120 and gp41 products of the env gene. Furthermore, the emergence of macrophagetropic variants in vivo was associated with specific pathologic manifestations in which the macrophage is the major infected cell type. Thus, major determinants of macrophage tropism reside in env, they can be complex in nature, and the presence of macrophage-tropic virus variants in vivo can influence the disease course and disease manifestations.

  2. Molecular Characterization of Clinical Isolates of Human Immunodeficiency Virus Resistant to the Protease Inhibitor Darunavir

    SciTech Connect

    Sasková, Klára Grantz; Koíek, Milan; Rezácová, Pavlína; Brynda, Jirí; Yashina, Tatyana; Kagan, Ron M.; Konvalinka, Jan

    2010-03-04

    Darunavir is the most recently approved human immunodeficiency virus (HIV) protease (PR) inhibitor (PI) and is active against many HIV type 1 PR variants resistant to earlier-generation PIs. Darunavir shows a high genetic barrier to resistance development, and virus strains with lower sensitivity to darunavir have a higher number of PI resistance-associated mutations than viruses resistant to other PIs. In this work, we have enzymologically and structurally characterized a number of highly mutated clinically derived PRs with high levels of phenotypic resistance to darunavir. With 18 to 21 amino acid residue changes, the PR variants studied in this work are the most highly mutated HIV PR species ever studied by means of enzyme kinetics and X-ray crystallography. The recombinant proteins showed major defects in substrate binding, while the substrate turnover was less affected. Remarkably, the overall catalytic efficiency of the recombinant PRs (5% that of the wild-type enzyme) is still sufficient to support polyprotein processing and particle maturation in the corresponding viruses. The X-ray structures of drug-resistant PRs complexed with darunavir suggest that the impaired inhibitor binding could be explained by change in the PR-inhibitor hydrogen bond pattern in the P2 binding pocket due to a substantial shift of the aminophenyl moiety of the inhibitor. Recombinant virus phenotypic characterization, enzyme kinetics, and X-ray structural analysis thus help to explain darunavir resistance development in HIV-positive patients.

  3. Risk to human health from a plethora of simian immunodeficiency viruses in primate bushmeat.

    PubMed

    Peeters, Martine; Courgnaud, Valerie; Abela, Bernadette; Auzel, Philippe; Pourrut, Xavier; Bibollet-Ruche, Frederic; Loul, Severin; Liegeois, Florian; Butel, Cristelle; Koulagna, Denis; Mpoudi-Ngole, Eitel; Shaw, George M; Hahn, Beatrice H; Delaporte, Eric

    2002-05-01

    To assess human exposure to Simian immunodeficiency virus (SIV) in west central Africa, we looked for SIV infection in 788 monkeys that were hunted in the rainforests of Cameroon for bushmeat or kept as pets. Serologic reactivity suggesting SIV infection was found in 13 of 16 primate species, including 4 not previously known to harbor SIV. Overall, 131 sera (16.6%) reacted strongly and an additional 34 (4.3%) reacted weakly with HIV antigens. Molecular analysis identified five new phylogenetic SIV lineages. These data document for the first time that a substantial proportion of wild monkeys in Cameroon are SIV infected and that humans who hunt and handle bushmeat are exposed to a plethora of genetically highly divergent viruses.

  4. Reduction of human immunodeficiency virus-infected cells from donor blood by leukocyte filtration.

    PubMed

    Rawal, B D; Busch, M P; Endow, R; Garcia-de-Lomas, J; Perkins, H A; Schwadron, R; Vyas, G N

    1989-06-01

    Several filters for leukocyte removal were evaluated in terms of their ability to reduce the cell-associated human immunodeficiency virus (HIV) load in units of blood either inoculated in vitro with lymphocytes from a chronically infected cell line or collected directly from seropositive donors. Filtration of the experimentally inoculated units of blood resulted in a 5.9 log 10 mean reduction (95% confidence interval:7.4-4.5) of tissue culture infectious units (TCIU) as assayed by end-point titration using the coculture assay. Filtration of the units of blood from anti-HIV positive donors lowered the infectivity by over 2 logs, as detected by the coculture and polymerase chain reaction (PCR) techniques. However, residual cell-associated virus was detected in the majority of experiments. Clinical studies are warranted to determine if leukocyte filtration of blood will reduce the risk of transfusion transmitted viral infections.

  5. Establishment of an indicator cell line for monitoring bovine immunodeficiency virus infection and inhibitor susceptibility.

    PubMed

    Yao, Xue; Su, Yang; Liu, Chang; Tan, Juan; Liu, Li; Geng, Yun-Qi; Qiao, Wen-Tao

    2010-01-01

    Indicator cell lines are useful biological tools for monitoring virus infection. In order to monitor infection with bovine immunodeficiency virus (BIV) in vitro, an indicator cell line derived from baby hamster kidney cells which contains integrated copies of an enhanced green fluorescent protein gene driven by the BIV long terminal repeat was constructed. The BIV indicator cell line, designated BIVE, can detect BIV infection more easily and effectively than the established method, which involves the observation of cell cytopathic effects. Furthermore, viral titration using an assay based on the indicator cells is 100 times more sensitive than the assay based on cytopathic effect. The finding that BIV can infect the hamster cell line expands the known host range of BIV in vitro. The BIV indicator cell line could also be used for the evaluation of the inhibitory effect of antiviral agents. The fusion inhibition effect of the heptad repeat 2 region of the BIV envelope protein could also be quantified.

  6. ADAR2 editing enzyme is a novel human immunodeficiency virus-1 proviral factor.

    PubMed

    Doria, Margherita; Tomaselli, Sara; Neri, Francesca; Ciafrè, Silvia Anna; Farace, Maria Giulia; Michienzi, Alessandro; Gallo, Angela

    2011-05-01

    The adenosine deaminases acting on RNA (ADAR) enzymes catalyse conversion of adenosine to inosine in dsRNA. A positive effect of ADAR1 on human immunodeficiency virus type 1 (HIV-1) replication has recently been reported. Here, we show that another ADAR enzyme, ADAR2, positively affects the replication process of HIV-1. We found that, analogously to ADAR1, ADAR2 enhances the release of progeny virions by an editing-dependent mechanism. However, differently from the ADAR1 enzyme, ADAR2 does not increase the infectious potential of the virus. Importantly, downregulation of ADAR2 in Jurkat cells significantly impairs viral replication. Therefore, ADAR2 shares some but not all proviral functions of ADAR1. These results suggest a novel role of ADAR2 as a viral regulator. PMID:21289159

  7. Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome

    PubMed Central

    Handley, Scott; Thackray, Larissa B.; Zhao, Guoyan; Presti, Rachel; Miller, Andrew; Droit, Lindsay; Abbink, Peter; Maxfield, Lori F.; Kambal, Amal; Duan, Erning; Stanley, Kelly; Kramer, Joshua; Macri, Sheila C.; Permar, Sallie R.; Schmitz, Joern E.; Mansfield, Keith; Brenchley, Jason M.; Veazey, Ronald S.; Stappenbeck, Thaddeus S.; Wang, David; Barouch, Dan H.; Virgin, Herbert W.

    2012-01-01

    SUMMARY Pathogenic simian immunodeficiency virus (SIV) infection is associated with enteropathy which likely contributes to AIDS progression. To identify candidate etiologies for AIDS enteropathy, we used next generation sequencing to define the enteric virome during SIV infection in nonhuman primates. Pathogenic, but not non-pathogenic, SIV infection was associated with significant expansion of the enteric virome. We identified at least 32 previously undescribed enteric viruses during pathogenic SIV infection and confirmed their presence using viral culture and PCR testing. We detected unsuspected mucosal adenovirus infection associated with enteritis as well as parvovirus viremia in animals with advanced AIDS, indicating the pathogenic potential of SIV-associated expansion of the enteric virome. No association between pathogenic SIV infection and the family-level taxonomy of enteric bacteria was detected. Thus, enteric viral infections may contribute to AIDS enteropathy and disease progression. These findings underline the importance of metagenomic analysis of the virome for understanding AIDS pathogenesis. PMID:23063120

  8. Detection of feline immunodeficiency virus in semen from seropositive domestic cats (Felis catus).

    PubMed Central

    Jordan, H L; Howard, J; Tompkins, W A; Kennedy-Stoskopf, S

    1995-01-01

    Electroejaculates from experimentally infected domestic cats were evaluated for the presence of feline immunodeficiency virus (FIV). Virus was isolated from cell-free seminal plasma and seminal cells by cocultivation with a feline interleukin-2-dependent CD4+ T-cell line, in which productive infection was demonstrated by syncytium formation and FIV gag p26 antigen secretion. In addition, an 868-bp segment of the FIV gag provirus gene was identified in cocultured cells by PCR and Southern analysis. A 582-bp fragment of the FIV gag provirus genome was detected by nested PCR and Southern analysis in nonfractionated seminal cells and in sperm purified by a swim-up procedure. This is the first report describing the detection of replication-competent FIV in cell-free and cell-associated forms in domestic cat semen. PMID:7474164

  9. Antibodies to CD4 in individuals infected with human immunodeficiency virus type 1.

    PubMed Central

    Kowalski, M; Ardman, B; Basiripour, L; Lu, Y C; Blohm, D; Haseltine, W; Sodroski, J

    1989-01-01

    The attachment of human immunodeficiency virus type 1 (HIV-1) to target cells is mediated by a specific interaction between the viral envelope glycoprotein (gp120) and the CD4 receptor. Here we report that approximately 10% of HIV-1-infected individuals produce antibodies that recognize the extracellular portion of the CD4 molecule. Carboxyl-terminal deletions of CD4 that do not affect HIV-1 gp120 binding eliminate recognition of CD4 by patient antisera. In contrast, mutations in the amino-terminal domain of CD4 that attenuate HIV-1 gp120 binding do not diminish CD4 recognition by patient antisera. These results suggest that HIV-1 infection can generate antibodies directed against a region of the viral receptor distinct from the virus-binding domain. Images PMID:2541442

  10. Vaginal transmission of chimeric simian/human immunodeficiency viruses in rhesus macaques.

    PubMed Central

    Lu, Y; Brosio, P; Lafaile, M; Li, J; Collman, R G; Sodroski, J; Miller, C J

    1996-01-01

    Chimeric simian/human immunodeficiency viruses (SHIVs) that express the env genes derived from distinct HIV type 1 (HIV-1) isolates were tested for the ability to infect rhesus macaques following intravaginal inoculation. SHIVs containing either the HIV-1 HXBc2 or the HIV-1 89.6 envelope glycoproteins were capable of replicating in intravenously inoculated rhesus macaques. However, intravaginal inoculation of animals with these two SHIVs resulted in infection only with the SHIV containing the HIV-1 89.6 glycoprotein. Thus, properties conferred by the envelope glycoproteins in the chimeric virus affect the ability of particular SHIVs to initiate a systemic infection following vaginal inoculation. These results provide indirect support for the hypothesis that the selection of specific viral variants occurs in the genital tracts of individuals exposed to HIV by sexual contact. PMID:8627782

  11. Lentiviral Gag Assembly Analyzed through the Functional Characterization of Chimeric Simian Immunodeficiency Viruses Expressing Different Domains of the Feline Immunodeficiency Virus Capsid Protein

    PubMed Central

    Esteva, María J.; Affranchino, José L.; González, Silvia A.

    2014-01-01

    To gain insight into the functional relationship between the capsid (CA) domains of the Gag polyproteins of simian and feline immunodeficiency viruses (SIV and FIV, respectively), we constructed chimeric SIVs in which the CA-coding region was partially or totally replaced by the equivalent region of the FIV CA. The phenotypic characterization of the chimeras allowed us to group them into three categories: the chimeric viruses that, while being assembly-competent, exhibit a virion-associated unstable FIV CA; a second group represented only by the chimeric SIV carrying the N-terminal domain (NTD) of the FIV CA which proved to be assembly-defective; and a third group constituted by the chimeric viruses that produce virions exhibiting a mature and stable FIV CA protein, and which incorporate the envelope glycoprotein and contain wild-type levels of viral genome RNA and reverse transcriptase. Further analysis of the latter group of chimeric SIVs demonstrated that they are non-infectious due to a post-entry impairment, such as uncoating of the viral core, reverse transcription or nuclear import of the preintegration complex. Furthermore, we show here that the carboxyl-terminus domain (CTD) of the FIV CA has an intrinsic ability to dimerize in vitro and form high-molecular-weight oligomers, which, together with our finding that the FIV CA-CTD is sufficient to confer assembly competence to the resulting chimeric SIV Gag polyprotein, provides evidence that the CA-CTD exhibits more functional plasticity than the CA-NTD. Taken together, our results provide relevant information on the biological relationship between the CA proteins of primate and nonprimate lentiviruses. PMID:25462889

  12. Heterogeneity in neutralization sensitivities of viruses comprising the simian immunodeficiency virus SIVsmE660 isolate and vaccine challenge stock.

    PubMed

    Lopker, Michael; Easlick, Juliet; Sterrett, Sarah; Decker, Julie M; Barbian, Hannah; Learn, Gerald; Keele, Brandon F; Robinson, James E; Li, Hui; Hahn, Beatrice H; Shaw, George M; Bar, Katharine J

    2013-05-01

    The sooty mangabey-derived simian immunodeficiency virus (SIV) strain E660 (SIVsmE660) is a genetically heterogeneous, pathogenic isolate that is commonly used as a vaccine challenge strain in the nonhuman primate (NHP) model of human immunodeficiency virus type 1 (HIV-1) infection. Though it is often employed to assess antibody-based vaccine strategies, its sensitivity to antibody-mediated neutralization has not been well characterized. Here, we utilize single-genome sequencing and infectivity assays to analyze the neutralization sensitivity of the uncloned SIVsmE660 isolate, individual viruses comprising the isolate, and transmitted/founder (T/F) viruses arising from low-dose mucosal inoculation of macaques with the isolate. We found that the SIVsmE660 isolate overall was highly sensitive to neutralization by SIV-infected macaque plasma samples (50% inhibitory concentration [IC50] < 10(-5)) and monoclonal antibodies targeting V3 (IC50 < 0.01 μg/ml), CD4-induced (IC50 < 0.1 μg/ml), CD4 binding site (IC50 ~ 1 μg/ml), and V4 (IC50, ~5 μg/ml) epitopes. In comparison, SIVmac251 and SIVmac239 were highly resistant to neutralization by these same antibodies. Differences in neutralization sensitivity between SIVsmE660 and SIVmac251/239 were not dependent on the cell type in which virus was produced or tested. These findings indicate that in comparison to SIVmac251/239 and primary HIV-1 viruses, SIVsmE660 generally exhibits substantially less masking of antigenically conserved Env epitopes. Interestingly, we identified a minor population of viruses (~10%) in both the SIVsmE660 isolate and T/F viruses arising from it that were substantially more resistant (>1,000-fold) to antibody neutralization and another fraction (~20%) that was intermediate in neutralization resistance. These findings may explain the variable natural history and variable protection afforded by heterologous Env-based vaccines in rhesus macaques challenged by high-dose versus low-dose SIVsmE660

  13. A fatal case of JC virus meningitis presenting with hydrocephalus in a human immunodeficiency virus-seronegative patient.

    PubMed

    Agnihotri, Shruti P; Wuthrich, Christian; Dang, Xin; Nauen, David; Karimi, Reza; Viscidi, Raphael; Bord, Evelyn; Batson, Stephanie; Troncoso, Juan; Koralnik, Igor J

    2014-07-01

    JC virus (JCV) is the etiologic agent of progressive multifocal leukoencephalopathy, JCV granule cell neuronopathy, and JCV encephalopathy. Whether JCV can also cause meningitis has not yet been demonstrated. We report a case of aseptic meningitis resulting in symptomatic hydrocephalus in a human immunodeficiency virus-seronegative patient. Brain imaging showed enlargement of ventricles but no parenchymal lesion. She had a very high JC viral load in the cerebrospinal fluid (CSF) and developed progressive cognitive dysfunction despite ventricular drainage. She was diagnosed with pancytopenia and passed away after 5.5 months. Postmortem examination revealed productive JCV infection of leptomeningeal and choroid plexus cells, and limited parenchymal involvement. Sequencing of JCV CSF strain showed an archetype-like regulatory region. Further studies of the role of JCV in aseptic meningitis and in idiopathic hydrocephalus are warranted.

  14. Evidence of feline immunodeficiency virus, feline leukemia virus, and Toxoplasma gondii in feral cats on Mauna Kea, Hawaii

    USGS Publications Warehouse

    Danner, R.M.; Goltz, Dan M.; Hess, S.C.; Banko, P.C.

    2007-01-01

    We determined prevalence to feline immunodeficiency virus (FIV) antibodies, feline leukemia virus (FeLV) antigen, and Toxoplasma gondii antibodies in feral cats (Felis catus) on Mauna Kea Hawaii from April 2002 to May 2004. Six of 68 (8.8%) and 11 of 68 (16.2%) cats were antibody positive to FIV and antigen positive for FeLV, respectively; 25 of 67 (37.3%) cats were seropositive to T. gondii. Antibodies to FeLV and T. gondii occurred in all age and sex classes, but FIV occurred only in adult males. Evidence of current or previous infections with two of these infectious agents was detected in eight of 64 cats (12.5%). Despite exposure to these infectious agents, feral cats remain abundant throughout the Hawaiian Islands. ?? Wildlife Disease Association 2007.

  15. Evidence of feline immunodeficiency virus, feline leukemia virus, and Toxoplasma gondii in feral cats on Mauna Kea, Hawaii.

    PubMed

    Danner, Raymond M; Goltz, Daniel M; Hess, Steven C; Banko, Paul C

    2007-04-01

    We determined prevalence to feline immunodeficiency virus (FIV) antibodies, feline leukemia virus (FeLV) antigen, and Toxoplasma gondii antibodies in feral cats (Felis catus) on Mauna Kea Hawaii from April 2002 to May 2004. Six of 68 (8.8%) and 11 of 68 (16.2%) cats were antibody positive to FIV and antigen positive for FeLV, respectively; 25 of 67 (37.3%) cats were seropositive to T. gondii. Antibodies to FeLV and T. gondii occurred in all age and sex classes, but FIV occurred only in adult males. Evidence of current or previous infections with two of these infectious agents was detected in eight of 64 cats (12.5%). Despite exposure to these infectious agents, feral cats remain abundant throughout the Hawaiian Islands.

  16. Evidence of feline immunodeficiency virus, feline leukemia virus, and Toxoplasma gondii in feral cats on Mauna Kea, Hawaii.

    PubMed

    Danner, Raymond M; Goltz, Daniel M; Hess, Steven C; Banko, Paul C

    2007-04-01

    We determined prevalence to feline immunodeficiency virus (FIV) antibodies, feline leukemia virus (FeLV) antigen, and Toxoplasma gondii antibodies in feral cats (Felis catus) on Mauna Kea Hawaii from April 2002 to May 2004. Six of 68 (8.8%) and 11 of 68 (16.2%) cats were antibody positive to FIV and antigen positive for FeLV, respectively; 25 of 67 (37.3%) cats were seropositive to T. gondii. Antibodies to FeLV and T. gondii occurred in all age and sex classes, but FIV occurred only in adult males. Evidence of current or previous infections with two of these infectious agents was detected in eight of 64 cats (12.5%). Despite exposure to these infectious agents, feral cats remain abundant throughout the Hawaiian Islands. PMID:17495320

  17. Feline immunodeficiency virus: an interesting model for AIDS studies and an important cat pathogen.

    PubMed Central

    Bendinelli, M; Pistello, M; Lombardi, S; Poli, A; Garzelli, C; Matteucci, D; Ceccherini-Nelli, L; Malvaldi, G; Tozzini, F

    1995-01-01

    The lentivirus feline immunodeficiency virus (FIV) is a widespread pathogen of the domestic cat that is mainly transmitted through bites, although other means of transmission are also possible. Its prevalence ranges from 1 to 10% in different cat populations throughout the world, thus representing a large reservoir of naturally infected animals. FIV resembles the human immunodeficiency