Science.gov

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. A Combination DNA and Attenuated Simian Immunodeficiency Virus Vaccine Strategy Provides Enhanced Protection from Simian/Human Immunodeficiency Virus-Induced Disease†

    PubMed Central

    Amara, Rama Rao; Patel, Kalpana; Niedziela, Genevieve; Nigam, Pragati; Sharma, Sunita; Staprans, Silvija I.; Montefiori, David C.; Chenareddi, Lakshmi; Herndon, James G.; Robinson, Harriet L.; McClure, Harold M.; Novembre, Francis J.

    2005-01-01

    Among the most effective vaccine candidates tested in the simian immunodeficiency virus (SIV)/macaque system, live attenuated viruses have been shown to provide the best protection from challenge. To investigate if preimmunization would increase the level of protection afforded by live attenuated SIVmac239Δnef (Δnef), macaques were given two priming immunizations of DNA encoding SIV Gag and Pol proteins, with control macaques receiving vector DNA immunizations. In macaques receiving the SIV DNA inoculation, SIV-specific cellular but not humoral responses were readily detectable 2 weeks after the second DNA inoculation. Following boosting with live attenuated virus, control of Δnef replication was superior in SIV-DNA-primed macaques versus vector-DNA-primed macaques and was correlated with higher levels of CD8+/gamma-interferon-positive and/or interleukin-2-positive cells. Challenge with an intravenous inoculation of simian/human immunodeficiency virus (SHIV) strain SHIV89.6p resulted in infection of all animals. However, macaques receiving SIV DNA as the priming immunizations had statistically lower viral loads than control animals and did not develop signs of disease, whereas three of seven macaques receiving vector DNA showed severe CD4+ T-cell decline, with development of AIDS in one of these animals. No correlation of immune responses to protection from disease could be derived from our analyses. These results demonstrate that addition of a DNA prime to a live attenuated virus provided better protection from disease following challenge than live attenuated virus alone. PMID:16306607

  3. Formation of a stable complex between the human immunodeficiency virus integrase protein and viral DNA.

    PubMed Central

    Vink, C; Lutzke, R A; Plasterk, R H

    1994-01-01

    The integrase (IN) protein of the human immunodeficiency virus (HIV) mediates two distinct reactions: (i) specific removal of two nucleotides from the 3' ends of the viral DNA and (ii) integration of the viral DNA into target DNA. Although IN discriminates between specific (viral) DNA and nonspecific DNA in physical in vitro assays, a sequence-specific DNA-binding domain could not be identified in the protein. A nonspecific DNA-binding domain, however, was found at the C terminus of the protein. We examined the DNA-binding characteristics of HIV-1 IN, and found that a stable complex of IN and viral DNA is formed in the presence of Mn2+. The IN-viral DNA complex is resistant to challenge by an excess of competitor DNA. Stable binding of IN to the viral DNA requires that the protein contains an intact N-terminal domain and active site (in the central region of the protein), in addition to the C-terminal DNA-binding domain. Images PMID:7937134

  4. Human immunodeficiency virus type 1 evolution in vivo tracked by DNA heteroduplex mobility assays.

    PubMed Central

    Delwart, E L; Sheppard, H W; Walker, B D; Goudsmit, J; Mullins, J I

    1994-01-01

    High mutation rates and strong selective pressures imposed on human immunodeficiency viruses in vivo result in the formation of pools of genetic variants known as quasispecies. DNA heteroduplex mobility and tracking analyses were used to monitor the generation of HIV sequence diversity, to estimate quasispecies complexity, and to assess the turnover of genetic variants to approach an understanding of the relationship between viral quasispecies evolution in vivo and disease progression. Proviral DNA pools were nearly homogeneous soon after sexual transmission. The emergence and clearance of individual variants then occurred at different rates in different individuals. High quasispecies complexity was found in long-term-infected, asymptomatic individuals, while rapid CD4+ cell decline and AIDS were often, but not always, associated with lower quasispecies complexity. Proviral genetic variation was often low following in vitro culture, because of the outgrowth of one or a few variants that often became more abundant only later as proviruses in peripheral blood mononuclear cells. These studies provide insight into the dynamics of human immunodeficiency virus sequence changes in vivo and illustrate the utility of heteroduplex analysis for the study of phenomena associated with rapid genetic changes. Images PMID:8084001

  5. 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.

  6. Chemokine-adjuvanted electroporated DNA vaccine induces substantial protection from simian immunodeficiency virus vaginal challenge.

    PubMed

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

    2016-01-01

    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 responses 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<0.01) remained either uninfected or had aborted infection compared with only 14% in the vaccine naïve group. The highest protection was observed in the CCR10L chemokines group, where six of nine animals had aborted infection and two remained uninfected, leading to 89% protection (P<0.001). 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

  7. 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

  8. 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: ...

  9. DNA vaccination using expression vectors carrying FIV structural genes induces immune response against feline immunodeficiency virus.

    PubMed

    Cuisinier, A M; Mallet, V; Meyer, A; Caldora, C; Aubert, A

    1997-07-01

    Following inactivated virus vaccination trials, the surface glycoprotein gp120 of the feline immunodeficiency virus (FIV) was considered as one of the determinants for protection. However, several vaccination trials using recombinant Env protein or some peptides failed to induce protection. To understand the role of the gp120 protein in vivo, we vaccinated cats with naked DNA coding for FIV structural proteins gp120 and p10. We analyzed the ability of these vaccinations to induce immune protection and to influence the onset of infection. Injection in cat muscles of expression vectors coding for the FIV gp120 protein induced a humoral response. Cats immunized twice with the gp120 gene showed different patterns after challenge. Two cats were, like the control cats, infected from the second week after infection onwards. The two others maintained a low proviral load with no modification of their antibody pattern. The immune response induced by gp120 DNA injection could control the level of viral replication. This protective-like immune response was not correlated to the humoral response. All the cats immunized with the gp120 gene followed by the p10 gene were infected, like the control cats, from the second week but they developed a complete humoral response against viral proteins after challenge. Furthermore, they showed a sudden but transient drop of the proviral load at 4 weeks after infection. Under these conditions, one injection of the p10 gene after one injection of the gp120 gene was not sufficient to stimulate protection. On the contrary, after a period, it seems to facilitate virus replication. PMID:9269051

  10. 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.

  11. Identification of the catalytic and DNA-binding region of the human immunodeficiency virus type I integrase protein.

    PubMed

    Vink, C; Oude Groeneger, A M; Plasterk, R H

    1993-03-25

    The integrase (IN) protein of the human immunodeficiency virus (HIV) is required for specific cleavage of the viral DNA termini, and subsequent integration of the viral DNA into target DNA. To identify the various domains of the IN protein we generated a series of IN deletion mutants as fusions to maltose-binding protein (MBP). The deletion mutants were tested for their ability to bind DNA, to mediate site-specific cleavage of the viral DNA ends, and to carry out integration and disintegration reactions. We found that the DNA-binding region resides between amino acids 200 and 270 of the 288-residues HIV-1 IN protein. The catalytic domain of the protein was mapped between amino acids 50 and 194. For the specific activities of IN, cleavage of the viral DNA and integration, both the DNA-binding domain and the conserved amino-terminal region of IN are required. These regions are dispensable however, for disintegration activity. PMID:8464733

  12. 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

  13. Efficient DNA Transfection Mediated by the C-Terminal Domain of Human Immunodeficiency Virus Type 1 Viral Protein R

    PubMed Central

    Kichler, Antoine; Pages, Jean-Christophe; Leborgne, Christian; Druillennec, Sabine; Lenoir, Christine; Coulaud, Dominique; Delain, Etienne; Le Cam, Eric; Roques, Bernard P.; Danos, Olivier

    2000-01-01

    Viral protein R (Vpr) of human immunodeficiency virus type 1 is produced late in the virus life cycle and is assembled into the virion through binding to the Gag protein. It is known to play a significant role early in the viral life cycle by facilitating the nuclear import of the preintegration complex in nondividing cells. Vpr is also able to interact with nucleic acids, and we show here that it induces condensation of plasmid DNA. We have explored the possibility of using these properties in DNA transfection experiments. We report that the C-terminal half of the protein (Vpr52–96) mediates DNA transfection in a variety of human and nonhuman cell lines with efficiencies comparable to those of the best-known transfection agents. Compared with polylysine, a standard polycationic transfection reagent, Vpr52–96 was 10- to 1,000-fold more active. Vpr52–96-DNA complexes were able to reach the cell nucleus through a pH-independent mechanism. These observations possibly identify an alternate pathway for DNA transfection. PMID:10823846

  14. 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.

  15. Site-specific hydrolysis and alcoholysis of human immunodeficiency virus DNA termini mediated by the viral integrase protein.

    PubMed Central

    Vink, C; Yeheskiely, E; van der Marel, G A; van Boom, J H; Plasterk, R H

    1991-01-01

    Before integration of the human immunodeficiency virus (HIV) DNA, two nucleotides are removed from the 3' ends of the viral DNA by the integrase (IN) protein. We studied the chemistry of this reaction, and found that IN mediates site-specific hydrolysis of a phosphodiester bond, resulting in release of a dinucleotide. A class of alcohols (including glycerol, 1,2-propanediol, but not 1,3-propanediol) can also act as nucleophile in this reaction, and likewise the alcoholic amino acids L-serine and L-threonine can be covalently linked to the dinucleotide. No evidence was found for a covalent linkage between the IN protein and this dinucleotide, suggesting that IN directs a single nucleophilic attack of water at the specific phosphodiester bond. Images PMID:1662361

  16. 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.

  17. Human immunodeficiency virus endocrinopathy

    PubMed Central

    Sinha, Uma; Sengupta, Nilanjan; Mukhopadhyay, Prasanta; Roy, Keshab Sinha

    2011-01-01

    Human immunodeficiency virus (HIV) endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients. PMID:22028995

  18. Protection from immunodeficiency virus challenges in rhesus macaques by multicomponent DNA immunization.

    PubMed

    Kim, J J; Yang, J S; Nottingham, L K; Lee, D J; Lee, M; Manson, K H; Wyand, M S; Boyer, J D; Ugen, K E; Weiner, D B

    2001-07-01

    Multicomponent DNA vaccines were used to elicit immune responses, which can impact viral challenge in three separate rhesus macaque models. Eight rhesus macaques were immunized with DNA vaccines for HIV env/rev and SIV gag/pol and were challenged intravenously with 10 animal infective doses (AID(50)) of cell-free SHIV IIIB. Three of eight immunized rhesus macaques were protected, exhibiting no detectable virus. Animals protected from nonpathogenic SHIVIIIB challenge were rested for extended periods of time and were rechallenged first with pathogenic SIV(mac239) and subsequently with pathogenic SHIV89.6P viruses. Following the pathogenic challenges, all three vaccinated animals were negative for viral coculture and antigenemia and were negative by PCR. In contrast, the control animals exhibited antigenemia by 2 weeks postchallenge and exhibited greater than 10 logs of virus/10(6) cells in limiting dilution coculture. The control animals exhibited CD4 cell loss and developed SIV-related wasting with high viral burden and subsequently failed to thrive. Vaccinated animals remained virus-negative and were protected from the viral load, CD4 loss, disease, and death. We observed strong Th1-type cellular immune responses in the protected macaques throughout the study, suggesting their important roles in protection. These studies support the finding that multicomponent DNA vaccines can directly impact viral replication and disease in a highly pathogenic challenge system, thus potentially broadening our strategies against HIV. PMID:11437655

  19. 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 ( ...

  20. Pharmacological Inhibition of Feline Immunodeficiency Virus (FIV)

    PubMed Central

    Mohammadi, Hakimeh; Bienzle, Dorothee

    2012-01-01

    Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses and causes an acquired immunodeficiency syndrome (AIDS) in domestic and non-domestic cats worldwide. Genome organization of FIV and clinical characteristics of the disease caused by the virus are similar to those of human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes and macrophages, and their replication cycle in infected cells is analogous. Due to marked similarity in genomic organization, virus structure, virus replication and disease pathogenesis of FIV and HIV, infection of cats with FIV is a useful tool to study and develop novel drugs and vaccines for HIV. Anti-retroviral drugs studied extensively in HIV infection have targeted different steps of the virus replication cycle: (1) inhibition of virus entry into susceptible cells at the level of attachment to host cell surface receptors and co-receptors; (2) inhibition of fusion of the virus membrane with the cell membrane; (3) blockade of reverse transcription of viral genomic RNA; (4) interruption of nuclear translocation and viral DNA integration into host genomes; (5) prevention of viral transcript processing and nuclear export; and (6) inhibition of virion assembly and maturation. Despite much success of anti-retroviral therapy slowing disease progression in people, similar therapy has not been thoroughly investigated in cats. In this article we review current pharmacological approaches and novel targets for anti-lentiviral therapy, and critically assess potentially suitable applications against FIV infection in cats. PMID:22754645

  1. Feline immunodeficiency virus infection.

    PubMed

    Pedersen, N C; Yamamoto, J K; Ishida, T; Hansen, H

    1989-05-01

    Feline immunodeficiency virus (FIV) (formerly feline T-lymphotropic lentivirus or FTLV) was first isolated from a group of cats in Petaluma, California in 1986. The virus is a typical lentivirus in gross and structural morphology. It replicates preferentially but not exclusively in feline T-lymphoblastoid cells, where it causes a characteristic cytopathic effect. The major structural proteins are 10, 17 (small gag), 28 (major core), 31 (endonuclease?), 41 (transmembrane?), 52 (core precursor polyprotein), 54/62 (reverse transcriptase?), and 110/130 (major envelope) kilodaltons in size. The various proteins are antigenically distinguishable from those of other lentiviruses, although serum from EIAV-infected horses will cross-react with some FIV antigens. Kittens experimentally infected with FIV manifest a transient (several days to 2 weeks) fever and neutropenia beginning 4 to 8 weeks after inoculation. This is associated with a generalized lymphadenopathy that persists for up to 9 months. Most cats recover from this initial phase of the disease and become lifelong carriers of the virus. Complete recovery does not occur to any extent in nature or in the laboratory setting. One experimentally infected cat died from a myeloproliferative disorder several months after infection. The terminal AIDS-like phase of the illness has been seen mainly in naturally infected cats. It appears a year or more following the initial infection in an unknown proportion of infected animals. FIV has been identified in cats from all parts of the world. It is most prevalent in high density populations of free roaming cats (feral and pet), and is very uncommon in closed purebred catteries. Male cats are twice as likely to become infected as females. Older male cats adopted as feral or stray animals are at the highest risk of infection, therefore. The infection rate among freely roaming cats rises throughout life, and reaches levels ranging from less than 1% to 12% or more depending on the

  2. Protection against feline immunodeficiency virus using replication defective proviral DNA vaccines with feline interleukin-12 and -18.

    PubMed

    Dunham, Stephen P; Flynn, J Norman; Rigby, Mark A; Macdonald, Julie; Bruce, Jennifer; Cannon, Celia; Golder, Matthew C; Hanlon, Linda; Harbour, David A; Mackay, Nancy A; Spibey, Norman; Jarrett, Oswald; Neil, James C

    2002-02-22

    A molecular clone of the Glasgow-8 isolate of FIV (FIVGL8) was rendered replication defective by an in-frame deletion in either reverse transcriptase (deltaRT) or integrase (deltaIN) genes for use as DNA vaccines. To test the ability of these multi-gene vaccines to protect against two feline immunodeficiency virus (FIV) isolates of differing virulence, cats were immunized using either DNA vaccine alone or co-administered with interleukin-12 (IL-12) and/or interleukin-18 (IL-18) cytokine DNA. Animals were challenged sequentially with FIV-Petaluma (FIVPET) an FIV isolate of relatively low virulence and subsequently with the more virulent FIVGL8. A proportion of vaccinates (5/18 deltaIN and 2/12 deltaRT) were protected against primary challenge with FIV(PET). Five of the vaccinated-protected cats were re-challenged with FIV(PET); four (all deltaIN) remained free of viraemia whilst all naive controls became viraemic. Following subsequent challenge with the more virulent FIVGL8 these four vaccinated-protected animals all became viraemic but showed lower proviral loads than naive cats. This study suggests that while our current DNA vaccines may not produce sterilizing immunity against more virulent isolates of FIV, they may nevertheless significantly reduce the impact of infection. PMID:11858854

  3. Establishment of a stable, inducible form of human immunodeficiency virus type 1 DNA in quiescent CD4 lymphocytes in vitro.

    PubMed Central

    Spina, C A; Guatelli, J C; Richman, D D

    1995-01-01

    Human immunodeficiency virus type 1 (HIV-1) possesses the ability to establish a complete infection in nondividing host cells. The capacity of HIV-1 to infect nondividing cells probably contributes significantly to its pathology in vivo, as reflected by infection of peripheral T lymphocytes, tissue macrophages, and microglial cells. However, the in vitro demonstration of the establishment of stable HIV-1 infection in quiescent T cells remains controversial. We have developed a primary T-cell model of acute HIV-1 infection of quiescent CD4 lymphocytes that demonstrates the development of a complete, reverse-transcribed form of virus that is stable for over 10 days in culture. To ensure that our primary cell culture was representative of a quiescent population, the CD4 lymphocyte targets were monitored for membrane expression of activation antigens and for shifts in cell cycle from G0/G1 to S/G2 phase. The presence of viral DNA fragments reflecting progressive reverse transcription was determined by PCR analysis. HIV entered primary CD4 cells rapidly, but viral DNA accumulated slowly in the resting cell cultures. DNA species containing regions of full-length reverse transcription were not detected until 3 to 5 days after infection. In parallel with the appearance of complete viral DNA, spliced RNA transcripts, predominantly of the nef species, were detected by reverse transcriptase PCR amplification. When infected CD4 cells were sorted on the basis of cell cycle analysis of DNA content, the accumulation of a complete viral DNA form was found to occur in both the purified G0/G1-phase cell subset and the cell fraction enriched for the minor S-phase subset. In contrast, spliced viral RNA products could be detected only in the enriched S-phase cell fraction. These results demonstrate that HIV-1 can infect and establish a complete, stable form of viral DNA in primary CD4 lymphocytes in vitro but is blocked from transcription in the absence of cell activation. The findings

  4. [Bovine immunodeficiency virus: short review].

    PubMed

    Bouillant, A M; Archambault, D

    1990-01-01

    A bovine visna-like virus was isolated by Van Der Maaten et al (1972) but it did not draw attention since, at that time, most efforts were directed towards research on bovine leukemia virus. However, new interest was shown on the bovine visna-like virus after the isolation of the human immunodeficiency virus (HIV), because of the urgent need for developing animal models for the acquired immunodeficiency syndrome (AIDS). The purpose of this paper is to describe the different stages of the identification of the bovine virus and to up-date knowledge about it. The bovine visna-like virus has recently been named the bovine immuno-deficiency-like virus (BIV) and is the sole bovine lentivirus known to-date. BIV shares morphologic, antigenic and genomic characteristics with other lentiviruses. It grows and induces large syncytia in vitro and generates virus-productive and latent infections in cell culture. It causes persistent infection and slow progressive disease in cattle and probably in sheep. As target cells of the virus are leukocytes, the type of which is unknown, perturbations of the immune system are expected. Consequently, BIV may potentiate the occurrence of secondary infections and play a role in retroviral, multiple infections. It is not oncogenic. Transmission appears to occur in cattle by contact, but evidence of transmission in human beings has not been shown. Finally, BIV may be a potential model in vitro and in vivo for HIV and AIDS. PMID:1963056

  5. Coordinate effects of human immunodeficiency virus type 1 protein Tat and cellular protein Puralpha on DNA replication initiated at the JC virus origin.

    PubMed

    Daniel, D C; Wortman, M J; Schiller, R J; Liu, H; Gan, L; Mellen, J S; Chang, C F; Gallia, G L; Rappaport, J; Khalili, K; Johnson, E M

    2001-07-01

    JC virus (JCV) causes progressive multifocal leukoencephalopathy, a demyelinating disease in brains of individuals with AIDS. Previous work has shown that the Tat protein, encoded by human immunodeficiency virus type 1 (HIV-1), can interact with cellular protein Puralpha to enhance both TAR-dependent HIV-1 transcription and JCV late gene transcription. Tat has been shown to activate JCV transcription through interaction with Puralpha, which binds to promoter sequence elements near the JCV origin of replication. DNA footprinting has shown that Puralpha and large T-antigen cooperatively interact at several binding sites in the origin and transcriptional control region. Overexpression of Puralpha inhibits replication initiated at the JCV origin by T-antigen. In transfected glial cells Tat reversed this inhibition and enhanced DNA replication. In an in vitro replication system maximal activation by Tat, more than sixfold the levels achieved with T-antigen alone, was achieved in the presence of Puralpha. Effects of mutant Tat proteins on both activation of replication and binding to Puralpha have revealed that Cys22 exerts a conformational effect that affects both activities. The origin of an archetypal strain of JCV was less susceptible to activation of replication by Tat relative to the rearranged Mad-1 strain. These results have revealed a previously undocumented role for Tat in DNA replication and have indicated a regulatory role for JCV origin auxiliary sequences in replication and activation by Tat. PMID:11413364

  6. A new label-free fluorescent sensor for human immunodeficiency virus detection based on exonuclease III-assisted quadratic recycling amplification and DNA-scaffolded silver nanoclusters.

    PubMed

    Yang, Wen; Tian, Jianniao; Wang, Lijun; Fu, Shui; Huang, Hongyun; Zhao, Yanchun; Zhao, Shulin

    2016-05-10

    A label-free and sensitive fluorescence biosensing platform for human immunodeficiency virus gene (HIV-DNA) detection has been fabricated based on luminescent DNA-scaffolded silver nanoclusters (DNA/AgNCs) and autonomous exonuclease III (Exo III)-assisted recycling signal amplification. One long-chain DNA (X-DNA) molecule can hybridize with two assistant DNA (F-DNA) molecules and one HIV-DNA molecule; after Exo III digests X-DNA to liberate F-DNA and HIV-DNA. F-DNA combines with P-DNA (template of DNA/AgNCs), accordingly, P-DNA is cut and the fluorescence of the system is quenched. This assay can finish in one-step without any labelling of the DNA chain or complex construction, and the strategy is sensitive with the detection limit as low as 35 pM. At the same time, the approach exhibits good selectivity even against a single base mismatch. What's more, the method is able to monitor HIV-DNA in real human serum samples; it holds great potential for early diagnosis in gene-related diseases. PMID:27053438

  7. 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

  8. 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.

  9. 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. PMID:1450349

  10. 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

  11. Platforms Formed from a Three-Dimensional Cu-Based Zwitterionic Metal-Organic Framework and Probe ss-DNA: Selective Fluorescent Biosensors for Human Immunodeficiency Virus 1 ds-DNA and Sudan Virus RNA Sequences.

    PubMed

    Yang, Shui-Ping; Chen, Shao-Rui; Liu, Shu-Wen; Tang, Xiao-Yan; Qin, Liang; Qiu, Gui-Hua; Chen, Jin-Xiang; Chen, Wen-Hua

    2015-12-15

    We herein report a water-stable three-dimensional Cu-based metal-organic framework (MOF) 1 supported by a tritopic quaternized carboxylate and 4,4'-dipyridyl sulfide as an ancillary ligand. This MOF exhibits unique pore shapes with aromatic rings, positively charged pyridinium and unsaturated Cu(II) cation centers, free carboxylates, tessellating H2O, and coordinating SO4(2-) on the pore surface. Compound 1 can interact with two carboxyfluorescein (FAM)-labeled single-stranded DNA sequences (probe ss-DNA, delineated as P-DNA) through electrostatic, π-stacking, and/or hydrogen-bonding interactions to form two P-DNA@1 systems, and thus quench the fluorescence of FAM via a photoinduced electron-transfer process. These P-DNA@1 systems can be used as effective fluorescent sensors for human immunodeficiency virus 1 double-stranded DNA and Sudan virus RNA sequences, respectively, with detection limits of 196 and 73 pM, respectively. PMID:26619043

  12. 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

  13. 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

  14. 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

  15. Functional characterization of a complex protein-DNA-binding domain located within the human immunodeficiency virus type 1 long terminal repeat leader region.

    PubMed Central

    Malim, M H; Fenrick, R; Ballard, D W; Hauber, J; Böhnlein, E; Cullen, B R

    1989-01-01

    Transcriptional trans activation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) by the viral tat trans activator is mediated by an LTR-specific sequence located immediately 3' to the start of transcription initiation. We have used a range of molecular techniques to examine DNA-protein interactions that occur in the vicinity of this cis-acting sequence. Our results demonstrate the existence of a sequence-specific DNA-protein interaction involving the HIV-1 leader DNA and map this binding event to between -2 and +21 base pairs relative to the HIV-1 LTR transcription start site. Evidence suggesting that this interaction involves three distinct protein-DNA contact sites extending along one side of the DNA helix is presented. Mutation of these sites was found to ablate protein-DNA binding yet was observed to have no effect on either the basal or tat trans-activated level of HIV-1 LTR-specific gene expression. We therefore conclude that this DNA-protein interaction has a function distinct from the regulation of HIV-1 LTR-specific gene expression. Images PMID:2545899

  16. 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

  17. 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.

  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. AIDS Vaccination Studies with an Ex Vivo Feline Immunodeficiency Virus Model: Analysis of the Accessory ORF-A Protein and DNA as Protective Immunogens

    PubMed Central

    Pistello, Mauro; Bonci, Francesca; Flynn, J. Norman; Mazzetti, Paola; Isola, Patrizia; Zabogli, Elisa; Camerini, Valentina; Matteucci, Donatella; Freer, Giulia; Pelosi, Paolo; Bendinelli, Mauro

    2006-01-01

    Determining which antigen must be included in AIDS vaccines to confer maximum protection is of utmost importance. In primate models, vaccines consisting of or including accessory viral proteins have yielded conflicting results. We investigated the protective potential of the accessory protein ORF-A of feline immunodeficiency virus (FIV) in cats. All three immunization strategies used (protein alone in alum adjuvant, DNA alone, or DNA prime-protein boost) clearly generated detectable immune responses. Upon challenge with ex vivo homologous FIV, ORF-A-immunized cats showed distinct enhancement of acute-phase infection relative to mock-immunized animals given alum or empty vector DNA. This effect was tentatively attributed to increased expression of the FIV receptor CD134 that was observed in the immunized cats. However, at subsequent sampling points that were continued for up to 10 months postchallenge, the average plasma viral loads of the ORF-A-immunized animals were slightly but consistently reduced relative to those of the control animals. In addition, CD4+ T lymphocytes in the circulation system declined more slowly in immunized animals than in control animals. These findings support the contention that immunization with lentiviral accessory proteins can improve the host's ability to control virus replication and slow down disease progression but also draw attention to the fact that even simple immunogens that eventually contribute to protective activity can transiently exacerbate subsequent lentiviral infections. PMID:16940498

  1. Presence of High-Risk Human Papillomavirus Genotype and Human Immunodeficiency Virus DNA in Anal High-Grade and Low-Grade Squamous Intraepithelial Lesions

    PubMed Central

    Liang, Chin-Yuan; Agsalda-Garcia, Melissa; Nagata, Ian; Milne, Cris; Zhu, Xuemei; Killeen, Jeffrey; Berry, J. Michael; Goodman, Marc T.

    2013-01-01

    Abstract Human immunodeficiency virus type 1 (HIV)-infected individuals are at risk for anal cancer, which is caused by human papillomavirus (HPV). The relationship between HIV and HPV that leads to anal cancer remains unclear. Recent data, however, suggest that the continued persistence of HIV DNA in patients treated with combined antiretroviral therapy leads to progression of HIV disease and other HIV-associated complications. Therefore, we investigated the relationship among anal low- and high-grade squamous intraepithelial lesions (LGSIL/HGSIL), high-risk HPV genotypes, and high HIV DNA copy numbers. Anal cytology specimens were assayed for HPV genotype and HIV DNA copy number. High-risk HPV genotypes (odds ratio OR: 3.73; 95% confidence interval CI: 1.08–12.91; p=0.04) and high HIV DNA copy numbers (ORper 100 HIV DNA copies: 1.13; 95% CI: 1.01–1.27, p=0.04) were both associated with LGSIL/HGSIL. When considering both high-risk HPV genotypes and HIV DNA copy numbers in predicting LGSIL/HGSIL, HIV DNA copy number was significant (ORper 100 HIV DNA copies: 1.09; 95% CI: 0.96–1.23, p=0.04) but not high-risk HPV genotypes (OR: 2.30, p=0.28), which did not change when adjusted for nadir CD4 cell count and HIV RNA levels. The findings warrant further investigation of HIV DNA and its relationship with HPV in LGSIL/HGSIL pathogenesis. PMID:22816619

  2. Towards detecting the human immunodeficiency virus using microcantilever sensors

    NASA Astrophysics Data System (ADS)

    Alodhayb, Abdullah; Brown, Nicole; Saydur Rahman, S. M.; Harrigan, Richard; Beaulieu, L. Y.

    2013-04-01

    Detecting the human immunodeficiency virus (HIV) is difficult because the virus is prone to mutations and is in low concentrations in the body. Inside the HIV virion are two well characterized single stranded (ss) RNA molecules (viral genome) that feature both variable regions and regions that are conserved under virus mutation. In this work, microcantilever sensors have been employed as potential HIV detectors by targeting a conserved sequence of the viral genome by attempting to detect target ssDNA and ssRNA molecules that are significantly longer than the ssDNA molecules functionalized on the cantilever.

  3. Typing Candida albicans oral isolates from human immunodeficiency virus-infected patients by multilocus enzyme electrophoresis and DNA fingerprinting.

    PubMed Central

    Boerlin, P; Boerlin-Petzold, F; Goudet, J; Durussel, C; Pagani, J L; Chave, J P; Bille, J

    1996-01-01

    A total of 189 Candida albicans isolates have been typed by multilocus enzyme electrophoresis. The results obtained confirm the clonal mode of reproduction of C. albicans. The C. albicans populations found in the oropharynx of human immunodeficiency virus (HIV)-infected patients, in the oropharynx of healthy carriers, or in association with invasive candidiasis could not be distinguished. No clone or group of clones could be associated with the appearance of clinical disorders or with a reduced in vitro susceptibility to the antifungal agent fluconazole. Multiple and sequential oral isolates from 24 HIV-infected patients were also typed by restriction enzyme analysis with the enzymes EcoRI and HinfI and by use of the Ca3 repetitive probe. The results obtained by the combination of all three typing methods show that all but one patient each carried a unique major C. albicans clone in their oropharynx. The 21 patients with sequential isolates had the same C. albicans clones in their throats during recurrent oropharyngeal candidiasis episodes, independently of clinical status or of changes of in vitro susceptibility to fluconazole. Finally, several isolates of the same C. albicans clone found simultaneously in the oropharynx of a patient may present different levels of susceptibility to fluconazole. PMID:8727910

  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. PMID:19458008

  5. Sequence heterogeneity of murine acquired immunodeficiency syndrome virus: the role of endogenous virus.

    PubMed

    Gayama, S; Vaupel, B A; Kanagawa, O

    1995-05-01

    A defective murine leukemia virus is the causative agent of murine acquired immunodeficiency syndrome (MAIDS). We have cloned cDNAs from both virus infected and non-infected cells using the PCR methods with primers corresponding to the franking sequence of the unique p12 gag gene. Sequence analysis of these cDNA clones revealed: (i) the presence of endogenous virus related to MAIDS virus in C57BL/6 mice, (ii) B cell lineage specific expression of endogenous virus and (iii) extensive heterogeneity of MAIDS virus recovered from virus infected cells due to the recombination of the related viruses (defective pathogenic virus, ecotropic virus and endogenous virus). These findings suggest that the creation of virus variants in infected cells may play an important role in virus pathogenesis and escape from immune attack during the development of MAIDS. PMID:7547712

  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. An interaction between the DNA-binding domains of RelA(p65) and Sp1 mediates human immunodeficiency virus gene activation.

    PubMed Central

    Perkins, N D; Agranoff, A B; Pascal, E; Nabel, G J

    1994-01-01

    Induction of human immunodeficiency virus type 1 (HIV-1) gene expression in stimulated T cells has been attributed to the activation of the transcription factor NF-kappa B. The twice-repeated kappa B sites within the HIV-1 long terminal repeat are in close proximity to three binding sites for Sp1. We have previously shown that a cooperative interaction of NF-kappa B with Sp1 is required for the efficient stimulation of HIV-1 transcription. In this report, we define the domains of each protein responsible for this effect. Although the transactivation domains seemed likely to mediate this interaction, we find, surprisingly, that this interaction occurs through the putative DNA-binding domains of both proteins. Sp1 specifically interacted with the amino-terminal region of RelA(p65). Similarly, RelA bound directly to the zinc finger region of Sp1. This interaction was specific and resulted in cooperative DNA binding to the kappa B and Sp1 sites in the HIV-1 long terminal repeat. Furthermore, the amino-terminal region of RelA did not associate with several other transcription factors, including MyoD, E12, or Kox15, another zinc finger protein. These findings suggest that the juxtaposition of DNA-binding sites promotes a specific protein interaction between the DNA-binding regions of these transcription factors. This interaction is required for HIV transcriptional activation and may provide a mechanism to allow for selective activation of kappa B-regulated genes. Images PMID:7935378

  8. The Epidemiology of Human Immunodeficiency Virus Infection.

    ERIC Educational Resources Information Center

    Glasner, Peter D.; Kaslow, Richard A.

    1990-01-01

    Reviews epidemiology and natural history of human immunodeficiency virus-Type 1 (HIV-1) infection. Discusses early and late clinical manifestations, diagnosis of infection, incubation and latency periods, and survival time. Reviews data from published literature on distribution of HIV infection in adult United States population and factors that…

  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. PMID:27394024

  11. 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

  12. Feline immunodeficiency virus in South America.

    PubMed

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

    2012-03-01

    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

  13. 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

  14. Human Immunodeficiency Virus and Related Retroviruses

    PubMed Central

    Nájera, Rafael; Herrera, M. I.; Andrés, R. de

    1987-01-01

    This paper summarizes the current knowledge on the human immunodeficiency virus (HIV) and related retroviruses, describing basic characteristics of this new group of viruses such as morphologic and genetic structure, biological and cultural properties, virus growth characteristics, genetic variability and virus replication. The discovery of new human and simian retroviruses has prompted the World Health Organization (WHO) to convene a group of experts to establish criteria for their characterization. This will allow rapid identification of new variants that may arise and allow public health measures to be implemented accordingly. Different approaches are made to nomenclature in view of the evolution of knowledge about these viruses, and a system of nomenclature has been proposed by the WHO working group. This system, inspired by the one developed for the influenza viruses, is practical and descriptive, providing information on the origins of the organism and its type. Images PMID:2829446

  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. 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.

  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. Intrinsic cellular defenses against human immunodeficiency viruses.

    PubMed

    Blanco-Melo, Daniel; Venkatesh, Siddarth; Bieniasz, Paul D

    2012-09-21

    Viral infections are often detrimental to host survival and reproduction. Consequently, hosts have evolved a variety of mechanisms to defend themselves against viruses. A component of this arsenal is a set of proteins, termed restriction factors, which exhibit direct antiviral activity. Among these are several classes of proteins (APOBEC3, TRIM5, Tetherin, and SAMHD1) that inhibit the replication of human and simian immunodeficiency viruses. Here, we outline the features, mechanisms, and evolution of these defense mechanisms. We also speculate on how restriction factors arose, how they might interact with the conventional innate and adaptive immune systems, and how an understanding of these intrinsic cellular defenses might be usefully exploited. PMID:22999946

  19. 78 FR 33848 - Draft Guidance for Industry on Human Immunodeficiency Virus-1 Infection: Developing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-05

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Human Immunodeficiency Virus... availability of a draft guidance for industry entitled ``Human Immunodeficiency Virus-1 Infection: Developing... guidance for industry entitled ``Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral...

  20. Practical diagnostic testing for human immunodeficiency virus.

    PubMed Central

    Jackson, J B; Balfour, H H

    1988-01-01

    Since the discovery of human immunodeficiency virus (HIV) as the causative agent of acquired immunodeficiency syndrome in 1983, there has been a proliferation of diagnostic tests. These assays can be used to detect the presence of HIV antibody, HIV antigen, HIV ribonucleic and deoxyribonucleic acids, and HIV reverse transcriptase. Enzyme-linked immunosorbent assays, Western blot, radioimmunoprecipitation assays, indirect immunofluorescence assays, reverse transcriptase assays, and several molecular hybridization techniques are currently available. Enzyme-linked immunosorbent, Western blot, and indirect immunofluorescence assays for HIV antibody are very sensitive, specific, and adaptable to most laboratories. An enzyme-linked immunosorbent assay for HIV antigen is also readily adaptable to most laboratories and will be commercially available soon. While the other assays are more tedious, they are valuable confirmatory tests and are suitable for reference laboratories. The biohazards of performing HIV testing can be minimized with proper biosafety measures. Images PMID:3060241

  1. Human immunodeficiency virus infection and the liver

    PubMed Central

    Crane, Megan; Iser, David; Lewin, Sharon R

    2012-01-01

    Liver disease in human immunodeficiency virus (HIV)-infected individuals encompasses the spectrum from abnormal liver function tests, liver decompensation, with and without evidence of cirrhosis on biopsy, to non-alcoholic liver disease and its more severe form, non-alcoholic steatohepatitis and hepatocellular cancer. HIV can infect multiple cells in the liver, leading to enhanced intrahepatic apoptosis, activation and fibrosis. HIV can also alter gastro-intestinal tract permeability, leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function. This review focuses on recent changes in the epidemiology, pathogenesis and clinical presentation of liver disease in HIV-infected patients, in the absence of co-infection with hepatitis B virus or hepatitis C virus, with a specific focus on issues relevant to low and middle income countries. PMID:22489261

  2. 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... Federal Register document for public comment that was published on September 24, 2012 (77 FR 58849), and a... HUMAN SERVICES Food and Drug Administration Human Immunodeficiency Virus Patient-Focused...

  3. 78 FR 46969 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-02

    ... of May 21, 2013 (78 FR 29755). In that notice, FDA requested public comment regarding patients... INFORMATION: I. Background In the Federal Register of May 21, 2013 (78 FR 29755), FDA announced the notice of... HUMAN SERVICES Food and Drug Administration Human Immunodeficiency Virus Patient-Focused...

  4. Cellular Restriction Factors of Feline Immunodeficiency Virus

    PubMed Central

    Zielonka, Jörg; Münk, Carsten

    2011-01-01

    Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors) or inhibit viral replication (restriction factors). Similar to Human immunodeficiency virus type 1 (HIV-1), the cat lentivirus Feline immunodeficiency virus (FIV) is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating. Of particular importance are the cellular proteins APOBEC3, TRIM5α and tetherin/BST-2. In general, lentiviruses counteract or escape their species’ own variant of the restriction factor, but are targeted by the orthologous proteins of distantly related species. Most of the knowledge regarding lentiviral restriction factors has been obtained in the HIV-1 system; however, much less is known about their effects on other lentiviruses. We describe here the molecular mechanisms that explain how FIV maintains its replication in feline cells, but is largely prevented from cross-species infections by cellular restriction factors. PMID:22069525

  5. Human Immunodeficiency Virus and Pulmonary Arterial Hypertension

    PubMed Central

    Ali, Alaa M.

    2013-01-01

    Human immunodeficiency virus- (HIV-) related pulmonary arterial hypertension (PAH) is a rare complication of HIV infection. The pathophysiology of HIV-related PAH is complex, with viral proteins seeming to play the major role. However, other factors, such as coinfection with other microorganisms and HIV-related systemic inflammation, might also contribute. The clinical presentation of HIV-related PAH and diagnosis is similar to other forms of pulmonary hypertension. Both PAH-specific therapies and HAART are important in HIV-related PAH management. Future studies investigating the pathogenesis are needed to discover new therapeutic targets and treatments. PMID:24027641

  6. 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

  7. 45 CFR 96.128 - Requirements regarding human immunodeficiency virus.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 1 2013-10-01 2013-10-01 false Requirements regarding human immunodeficiency virus. 96.128 Section 96.128 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... human immunodeficiency virus. (a) In the case of a designated State as described in paragraph (b)...

  8. 45 CFR 96.128 - Requirements regarding human immunodeficiency virus.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Requirements regarding human immunodeficiency virus. 96.128 Section 96.128 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... human immunodeficiency virus. (a) In the case of a designated State as described in paragraph (b)...

  9. 45 CFR 96.128 - Requirements regarding human immunodeficiency virus.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Requirements regarding human immunodeficiency virus. 96.128 Section 96.128 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... human immunodeficiency virus. (a) In the case of a designated State as described in paragraph (b)...

  10. 45 CFR 96.128 - Requirements regarding human immunodeficiency virus.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Requirements regarding human immunodeficiency virus. 96.128 Section 96.128 Public Welfare Department of Health and Human Services GENERAL... human immunodeficiency virus. (a) In the case of a designated State as described in paragraph (b)...

  11. 45 CFR 96.128 - Requirements regarding human immunodeficiency virus.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Requirements regarding human immunodeficiency virus. 96.128 Section 96.128 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... human immunodeficiency virus. (a) In the case of a designated State as described in paragraph (b)...

  12. DNA-dependent protein kinase interacts functionally with the RNA polymerase II complex recruited at the human immunodeficiency virus (HIV) long terminal repeat and plays an important role in HIV gene expression.

    PubMed

    Tyagi, Shilpi; Ochem, Alex; Tyagi, Mudit

    2011-07-01

    DNA-dependent protein kinase (DNA-PK), a nuclear protein kinase that specifically requires association with DNA for its kinase activity, plays important roles in the regulation of different DNA transactions, including transcription, replication and DNA repair, as well as in the maintenance of telomeres. Due to its large size, DNA-PK is also known to facilitate the activities of other factors by providing the docking platform at their site of action. In this study, by running several chromatin immunoprecipitation assays, we demonstrate the parallel distribution of DNA-PK with RNA polymerase II (RNAP II) along the human immunodeficiency virus (HIV) provirus before and after activation with tumour necrosis factor alpha. The association between DNA-PK and RNAP II is also long-lasting, at least for up to 4 h (the duration analysed in this study). Knockdown of endogenous DNA-PK using specific small hairpin RNAs expressed from lentiviral vectors resulted in significant reduction in HIV gene expression and replication, demonstrating the importance of DNA-PK for HIV gene expression. Sequence analysis of the HIV-1 Tat protein revealed three potential target sites for phosphorylation by DNA-PK and, by using kinase assays, we confirmed that Tat is an effective substrate of DNA-PK. Through peptide mapping, we found that two of these three potential phosphorylation sites are recognized and phosphorylated by DNA-PK. Mutational studies on the DNA-PK target sites of Tat further demonstrated the functional significance of the Tat-DNA-PK interaction. Thus, overall our results clearly demonstrate the functional interaction between DNA-PK and RNAP II during HIV transcription. PMID:21450944

  13. Human immunodeficiency virus encephalitis in SCID mice.

    PubMed Central

    Persidsky, Y.; Limoges, J.; McComb, R.; Bock, P.; Baldwin, T.; Tyor, W.; Patil, A.; Nottet, H. S.; Epstein, L.; Gelbard, H.; Flanagan, E.; Reinhard, J.; Pirruccello, S. J.; Gendelman, H. E.

    1996-01-01

    The human immunodeficiency virus (HIV) is neuroinvasive and commonly causes cognitive and motor deficits during the later stages of viral infection. (referred to as HIV dementia). The mechanism(s) for disease revolves around secretory products produced from immune-activated brain macrophages/microglia. Recently, we developed an animal model system for HIV dementia that contains xenografts of HIV-1-infected cells inoculated into brains of mice with severe combined immunodeficiency (SCID). This animal system was used to quantitatively evaluate HIV-induced neuropathology. Xenografts of HIV-1-infected human monocytes (placed into the putamen and cortex of SCID mice) remained viable for 5 weeks. HIV-1 p24 antigen expression in mouse brain was persistent. Progressive inflammatory responses (including astrogliosis and cytokine production), which began at 3 days, peaked at day 12. The range of astrocyte proliferative reactions exceeded the inoculation site by > 1000 microns. Brains with virus-infected monocytes showed a > or = 1.6-fold increase in glial fibrillary acidic protein (staining distribution and intensity) as compared with similarly inoculated brains with uninfected control monocytes. These findings paralleled the accumulation and activation of murine microglia (increased branching of cell processes, formation of microglial nodules, interleukin (IL)-1 beta and IL-6 expression). An inflammatory reaction of human monocytes (as defined by HLA-DR, IL-1 beta, IL-6, and tumor necrosis factor-alpha expression) and neuronal injury (apoptosis) also developed after virus-infected monocyte xenograft placement into mouse brain tissue. These data, taken together, demonstrate that this SCID mouse model of HIV-1 neuropathogenesis can reproduce key aspects of disease (virus-infected macrophages, astrocytosis, microglial activation, and neuronal damage). This model may serve as an important means for therapeutic development directed toward improving mental function in HIV

  14. 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

  15. Human immunodeficiency virus induced oral candidiasis

    PubMed Central

    Warrier, S. Aravind; Sathasivasubramanian, S.

    2015-01-01

    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. PMID:26538978

  16. Genetic variability in human immunodeficiency viruses.

    PubMed

    Alizon, M; Montagnier, L

    1987-01-01

    The genetic polymorphism of the human immunodeficiency virus (HIV) has been established. In addition to the nucleic acid variations responsible for the restriction map polymorphism, isolates of HIV differ significantly at the protein level, especially in the envelope, in terms of amino acid substitutions and reciprocal insertions-deletions. In this investigation, molecular cloning and nucleotide sequencing of the genomes of 2 HIV isolates obtained from patients in Zaire were carried out. The 1st isolate was recovered in 1983 from a 24-year-old woman with acquired immunodeficiency syndrome (AIDS); the 2nd was isolated in 1985 from a 7-year-old boy with AIDS-related complex (ARC). The genetic organization of these isolates was identical to that found in other HIV isolates from the US and Europe, particularly in terms of the conservation of the central region located between the pol and env genes composed of a series of overlapping open reading frames. There were, however, substantial differences in the primary structure of the viral proteins, with env being more variable than the gag and pol genes. Alignment of the envelopes revealed hypervariable domains with a great number of mutations and reciprocal insertions and deletions. Overall, this analysis suggests that the African and American HIV infections have a common origin given their identical genetic organization. The sequence variability reflects a divergent evolutionary process, and the fact that the 2 Zairian isolates were more divergent than American isolates studied by others indicates a longer evolution of HIV in Africa. An essential research goal is to identify the HIV envelope domains responsible for the virus-cellular surface antigen interaction since an immune response against these epitopes could elicit neutralizing antibodies for use in a vaccine. PMID:3439717

  17. Co-administration of plasmid-encoded granulocyte-macrophage colony-stimulating factor increases human immunodeficiency virus-1 DNA vaccine-induced polyfunctional CD4+ T-cell responses

    PubMed Central

    Santana, Vinicius Canato; Almeida, Rafael Ribeiro; Ribeiro, Susan Pereira; Ferreira, Luís Carlos de Souza; Kalil, Jorge; Rosa, Daniela Santoro; Cunha-Neto, Edecio

    2015-01-01

    T-cell based vaccines against human immunodeficiency virus (HIV) generate specific responses that may limit both transmission and disease progression by controlling viral load. Broad, polyfunctional, and cytotoxic CD4+T-cell responses have been associated with control of simian immunodeficiency virus/HIV-1 replication, supporting the inclusion of CD4+ T-cell epitopes in vaccine formulations. Plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF) co-administration has been shown to induce potent CD4+ T-cell responses and to promote accelerated priming and increased migration of antigen-specific CD4+ T-cells. However, no study has shown whether co-immunisation with pGM-CSF enhances the number of vaccine-induced polyfunctional CD4+ T-cells. Our group has previously developed a DNA vaccine encoding conserved, multiple human leukocyte antigen (HLA)-DR binding HIV-1 subtype B peptides, which elicited broad, polyfunctional and long-lived CD4+ T-cell responses. Here, we show that pGM-CSF co-immunisation improved both magnitude and quality of vaccine-induced T-cell responses, particularly by increasing proliferating CD4+ T-cells that produce simultaneously interferon-γ, tumour necrosis factor-α and interleukin-2. Thus, we believe that the use of pGM-CSF may be helpful for vaccine strategies focused on the activation of anti-HIV CD4+ T-cell immunity. PMID:26602876

  18. Co-administration of plasmid-encoded granulocyte-macrophage colony-stimulating factor increases human immunodeficiency virus-1 DNA vaccine-induced polyfunctional CD4+ T-cell responses.

    PubMed

    Santana, Vinicius Canato; Almeida, Rafael Ribeiro; Ribeiro, Susan Pereira; Ferreira, Luís Carlos de Souza; Kalil, Jorge; Rosa, Daniela Santoro; Cunha-Neto, Edecio

    2015-12-01

    T-cell based vaccines against human immunodeficiency virus (HIV) generate specific responses that may limit both transmission and disease progression by controlling viral load. Broad, polyfunctional, and cytotoxic CD4+T-cell responses have been associated with control of simian immunodeficiency virus/HIV-1 replication, supporting the inclusion of CD4+ T-cell epitopes in vaccine formulations. Plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF) co-administration has been shown to induce potent CD4+ T-cell responses and to promote accelerated priming and increased migration of antigen-specific CD4+ T-cells. However, no study has shown whether co-immunisation with pGM-CSF enhances the number of vaccine-induced polyfunctional CD4+ T-cells. Our group has previously developed a DNA vaccine encoding conserved, multiple human leukocyte antigen (HLA)-DR binding HIV-1 subtype B peptides, which elicited broad, polyfunctional and long-lived CD4+ T-cell responses. Here, we show that pGM-CSF co-immunisation improved both magnitude and quality of vaccine-induced T-cell responses, particularly by increasing proliferating CD4+ T-cells that produce simultaneously interferon-γ, tumour necrosis factor-α and interleukin-2. Thus, we believe that the use of pGM-CSF may be helpful for vaccine strategies focused on the activation of anti-HIV CD4+ T-cell immunity. PMID:26602876

  19. Syphilis? An Unusual Cause of Surgical Emergency in a Human Immunodeficiency Virus-Infected Man

    PubMed Central

    Bender Ignacio, Rachel A.; Koch, Lisa L.; Dhanireddy, Shireesha; Charmie Godornes, B.; Lukehart, Sheila A.; Marrazzo, Jeanne M.

    2015-01-01

    We report on a human immunodeficiency virus-infected man undergoing urgent anorectal surgery, with multi-centimeter fungating masses discovered inside the anus. Initial pathology was inconclusive. After the patient developed a disseminated rash postoperatively determined to be secondary syphilis, the anorectal pathology was reviewed and Treponema pallidum DNA was amplified by polymerase chain reaction from the mass. PMID:26213693

  20. 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. PMID:17265140

  1. 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

  2. Bacterial Respiratory Infections Complicating Human Immunodeficiency Virus.

    PubMed

    Feldman, Charles; Anderson, Ronald

    2016-04-01

    Opportunistic bacterial and fungal infections of the lower respiratory tract, most commonly those caused by Streptococcus pneumoniae (the pneumococcus), Mycobacterium tuberculosis, and Pneumocystis jirovecii, remain the major causes of mortality in those infected with human immunodeficiency virus (HIV). Bacterial respiratory pathogens most prevalent in those infected with HIV, other than M. tuberculosis, represent the primary focus of the current review with particular emphasis on the pneumococcus, the leading cause of mortality due to HIV infection in the developed world. Additional themes include (1) risk factors; (2) the predisposing effects of HIV-mediated suppression on pulmonary host defenses, possibly intensified by smoking; (3) clinical and laboratory diagnosis, encompassing assessment of disease severity and outcome; and (4) antibiotic therapy. The final section addresses current recommendations with respect to pneumococcal immunization in the context of HIV infection, including an overview of the rationale underpinning the current "prime-boost" immunization strategy based on sequential administration of pneumococcal conjugate vaccine 13 and pneumococcal polysaccharide vaccine 23. PMID:26974299

  3. 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

  4. 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

  5. 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)

  6. Macrophages in Progressive Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections.

    PubMed

    DiNapoli, Sarah R; Hirsch, Vanessa M; Brenchley, Jason M

    2016-09-01

    The cells that are targeted by primate lentiviruses (HIV and simian immunodeficiency virus [SIV]) are of intense interest given the renewed effort to identify potential cures for HIV. These viruses have been reported to infect multiple cell lineages of hematopoietic origin, including all phenotypic and functional CD4 T cell subsets. The two most commonly reported cell types that become infected in vivo are memory CD4 T cells and tissue-resident macrophages. Though viral infection of CD4 T cells is routinely detected in both HIV-infected humans and SIV-infected Asian macaques, significant viral infection of macrophages is only routinely observed in animal models wherein CD4 T cells are almost entirely depleted. Here we review the roles of macrophages in lentiviral disease progression, the evidence that macrophages support viral replication in vivo, the animal models where macrophage-mediated replication of SIV is thought to occur, how the virus can interact with macrophages in vivo, pathologies thought to be attributed to viral replication within macrophages, how viral replication in macrophages might contribute to the asymptomatic phase of HIV/SIV infection, and whether macrophages represent a long-lived reservoir for the virus. PMID:27307568

  7. 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

  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

    ... Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV... Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) through Solid Organ Transplantation (Draft Guideline). The Draft Guideline can...

  9. 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

  10. 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.

  11. Neurosyphilis in a Man with Human Immunodeficiency Virus

    PubMed Central

    Sadeghani, Khosro; Kallini, Joseph R.

    2014-01-01

    The authors describe a 33-year-old man with human immunodeficiency virus who developed erythematous macules on the palms and soles with subsequent headaches, papilledema, and iritis. They review the salient characteristics of neurosyphilis with a focus on human immunodeficiency virus-positive individuals. The incidence of syphilis has increased since the year 2000 in African Americans, Hispanics, and men who have sex with men. Treponema pallidum is the causative agent of this disease—a fastidious, slowly growing, microaerophilic spirochete. Sexual contact is the most common mode of transmission. The rapid plasma reagin, Venereal Disease Research Laboratory assay, and fluorescent treponemal antibody absorption assay are commonly used to diagnose syphilis. The mainstay treatment is penicillin. Special considerations exist in the natural history and management of syphilis in the setting of human immunodeficiency virus. PMID:25161759

  12. 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

  13. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  14. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  15. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  16. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  17. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  18. 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

  19. 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.

  20. The regulation of human immunodeficiency virus type-1 gene expression.

    PubMed

    Kingsman, S M; Kingsman, A J

    1996-09-15

    Despite 15 years of intensive research we still do not have an effective treatment for AIDS, the disease caused by human immunodeficiency virus (HIV). Recent research is, however, revealing some of the secrets of the replication cycle of this complex retrovirus, and this may lead to the development of novel antiviral compounds. In particular the virus uses strategies for gene expression that seem to be unique in the eukaryotic world. These involve the use of virally encoded regulatory proteins that mediate their effects through interactions with specific viral target sequences present in the messenger RNA rather than in the proviral DNA. If there are no cellular counterparts of these RNA-dependent gene-regulation pathways then they offer excellent targets for the development of antiviral compounds. The viral promoter is also subject to complex regulation by combinations of cellular factors that may be functional in different cell types and at different cell states. Selective interference of specific cellular factors may also provide a route to inhibiting viral replication without disrupting normal cellular functions. The aim of this review is to discuss the regulation of HIV-1 gene expression and, as far as it is possible, to relate the observations to viral pathogenesis. Some areas of research into the regulation of HIV-1 replication have generated controversy and rather than rehearsing this controversy we have imposed our own bias on the field. To redress the balance and to give a broader view of HIV-1 replication and pathogenesis we refer you to a number of excellent reviews [Cullen, B. R. (1992) Microbiol. Rev. 56, 375-394; Levy, J. A. (1993) Microbiol. Rev. 57, 183-394; Antoni, B. A., Stein, S. & Rabson, A. B. (1994) Adv. Virus Res. 43, 53-145; Rosen, C. A. & Fenyoe, E. M. (1995) AIDS (Phila.) 9, S1-S3]. PMID:8856047

  1. Genetic Diversity of Pneumocystis carinii Isolated from Human Immunodeficiency Virus-Positive Patients in Turin, Italy

    PubMed Central

    Volpe, Gisella; Sbaiz, Luca; Avanzini, Claudio; Caramello, Pietro; Savoia, Dianella

    2001-01-01

    By DNA sequence analysis we identified two new strain types and five novel sporadic variations among 25 isolates of Pneumocystis carinii f. sp. hominis obtained from 19 human immunodeficiency virus-positive patients. Of these, 13 were infected with a single strain and 6 were coinfected. Fifteen different combination types were identified among the 18 strains for which complete molecular typing was accomplished. PMID:11474032

  2. 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"…

  3. 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

  4. 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

  5. [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

  6. 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

  7. Symptoms of Autonomic Dysfunction in Human Immunodeficiency Virus.

    PubMed

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

    2015-09-01

    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

  8. Aquagenic urticaria and human immunodeficiency virus infection: treatment with stanozolol.

    PubMed

    Fearfield, L A; Gazzard, B; Bunker, C B

    1997-10-01

    We report the first case of aquagenic urticaria in a patient with human immunodeficiency virus (HIV) infection. This is a rare physical urticaria not previously described in this context. The disorder proved unamenable to conventional treatment with antihistamines, but did respond dramatically to stanozolol, suggesting a novel indication for this anabolic steroid. PMID:9390343

  9. 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

  10. 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

  11. 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.

  12. Economic consequences for Medicaid of human immunodeficiency virus infection

    PubMed Central

    Baily, Mary Ann; Bilheimer, Linda; Wooldridge, Judith; well, Kathryn Lang; Greenberg, Warren

    1990-01-01

    Medicaid is currently a major source of financing for health care for those with acquired immunodeficiency syndrome (AIDS) and to a lesser extent, for those with other manifestations of human immunodeficiency virus (HIV) infection. It is likely to become even more important in the future. This article focuses on the structure of Medicaid in the context of the HIV epidemic, covering epidemiological issues, eligibility, service coverage and use, and reimbursement. A simple methodology for estimating HI\\'-related Medicaid costs under alternative assumptions about the future is also explained. PMID:10113503

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

    PubMed

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

    2015-12-01

    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

  14. 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

  15. Human Immunodeficiency Virus and Liver Disease Forum 2010: Conference Proceedings

    PubMed Central

    Sherman, Kenneth E.; Thomas, David L.; Chung, Raymond T.

    2013-01-01

    Liver disease continues to represent a critical mediator of morbidity and mortality in those with human immunodeficiency virus (HIV) infection. The frequent presence and overlap of concomitant injurious processes, including hepatitis C virus and hepatitis B virus infections, hepatoxicity associated with antiretroviral therapeutic agents, alcohol, and other toxins, in the setting of immunosuppression lead to rapid fibrotic progression and early development of end-stage liver disease. This conference summary describes the proceedings of a state-of-the-art gathering of international experts designed to highlight the status of current research in epidemiology, natural history, pathogenesis, and treatment of HIV and liver disease. PMID:21898501

  16. 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

  17. Breakthrough Virus Neutralization Resistance as a Correlate of Protection in a Nonhuman Primate Heterologous Simian Immunodeficiency Virus Vaccine Challenge Study

    PubMed Central

    Lee, Fang-Hua; Mason, Rosemarie; Welles, Hugh; Learn, Gerald H.; Keele, Brandon F.; Roederer, Mario

    2015-01-01

    ABSTRACT Comprehensive assessments of immune correlates of protection in human immunodeficiency virus (HIV) vaccine trials are essential to vaccine design. Neutralization sieve analysis compares the neutralization sensitivity of the breakthrough transmitted/founder (TF) viruses from vaccinated and control animals to infer the molecular mechanisms of vaccine protection. Here, we report a robust neutralization sieve effect in a nonhuman primate simian immunodeficiency virus (SIV) vaccine trial (DNA prime/recombinant adenovirus type 5 [rAd5] boost) (VRC-10-332) that demonstrated substantial protective efficacy and revealed a genetic signature of neutralization resistance in the C1 region of env. We found significant enrichment for neutralization resistance in the vaccine compared to control breakthrough TF viruses when tested with plasma from vaccinated study animals, plasma from chronically SIV-infected animals, and a panel of SIV-specific monoclonal antibodies targeting six discrete Env epitopes (P < 0.008 for all comparisons). Neutralization resistance was significantly associated with the previously identified genetic signature of resistance (P < 0.0001), and together, the results identify virus neutralization as a correlate of protection. These findings further demonstrate the in vivo relevance of our previous in vitro analyses of the SIVsmE660 challenge stock, which revealed a broad range of neutralization sensitivities of its component viruses. In sum, this report demonstrates proof-of-concept that phenotypic sieve analyses can elucidate mechanistic correlates of immune protection following vaccination and raises a cautionary note for SIV and SHIV (simian-human immunodeficiency virus) vaccine studies that employ challenge strains with envelope glycoproteins that fail to exhibit neutralization resistance profiles typical of TF viruses. IMPORTANCE With more than 2 million new infections annually, the development of an effective vaccine against HIV-1 is a global

  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. Total knee arthroplasty in human immunodeficiency virus-infected hemophiliacs.

    PubMed

    Unger, A S; Kessler, C M; Lewis, R J

    1995-08-01

    Twenty-six knee arthroplasties were performed in 15 patients with hemophilia A and human immunodeficiency virus infection from 1984 to 1991. Patient age range was 27 to 48 years. After an average follow-up period of 6.4 years (range, 1-9 years) all patients were alive and none of the implants had become infected. T4 lymphocyte counts showed some deterioration, which was not clinically significant. All of the patients were improved following surgery. Nineteen implants were rated excellent, four good, and three fair. Infection with human immunodeficiency virus did not adversely affect the clinical outcome of knee arthroplasty at follow-up periods up to 9 years. PMID:8523002

  20. 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.

  1. 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

  2. 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.

  3. Neurocysticercosis and human immunodeficiency virus infection: a case report.

    PubMed

    Chianura, Leonardo; Sberna, Maurizio; Moioli, Cristina; Villa, Maria Riccarda; Orcese, Carloandrea; Causarano, Renzo

    2006-01-01

    Ecuador is considered a holoendemic high-risk area for the transmission of cysticercosis. Moreover, the progression of human immunodeficiency virus (HIV) occurs worldwide. We present a case of simultaneous diagnosis of cysticercosis and HIV infection in a 22-year-old Ecuadorian immigrant. We would postulate that with the increasing HIV incidence in endemic areas of cysticercosis, the simultaneous diagnosis of both diseases is an event to be expected. PMID:17107432

  4. Simplified testing for antibodies to human immunodeficiency virus.

    PubMed

    Pagcharoenpol, P; Burgess-Cassler, A; Schramm, W

    1996-04-01

    Test strips for the detection of antibodies to human immunodeficiency virus type 1 were investigated using specimens from risk groups in Thailand (141 reactive; 445 nonreactive) in a local Thai laboratory. The diagnostic sensitivity and specificity were both 100%. Using a set of seroconversion panels, the sensitivity of the test strips was within the range of sensitivities obtained with enzyme immunoassays. The test was developed for performance at decentralized settings under nonlaboratory conditions. PMID:8815120

  5. [Lopinavir/ritonavir in human immunodeficiency virus-infected women].

    PubMed

    Téllez, María Jesús

    2014-11-01

    There are clear sex-related biological differences between men and women. Diseases that affect the two sexes differently are studied separately. However, some diseases affect both men and women, but their incidence or outcome are clearly different. In human immunodeficiency virus infection, the potential differences in the effects of antiretroviral therapy are poorly characterized and few studies have been designed to elucidate these differences. Moreover, women are usually poorly represented in clinical trials of antiretroviral drugs. PMID:25542872

  6. 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.

  7. Oral lesions associated with human immunodeficiency virus disease.

    PubMed

    Patton, Lauren L

    2013-10-01

    Human immunodeficiency virus (HIV)-associated oral disease among people living with HIV infection includes oral candidiasis, oral hairy leukoplakia, Kaposi sarcoma, oral warts, herpes simplex virus ulcers, major aphthous ulcers or ulcers not otherwise specified, HIV salivary gland disease, and atypical gingival and periodontal diseases. Diagnosis of some oral lesions is based on clinical appearance and behavior, whereas others require biopsy, culture, or imaging for definitive diagnosis. Management strategies including pharmacologic and nonpharmacologic approaches are discussed in this article. Dentists also need to be cognizant of the potential oral side effects of HIV antiretroviral medications. PMID:24034072

  8. Update on Human Immunodeficiency Virus (HIV)-2 Infection

    PubMed Central

    Campbell-Yesufu, Omobolaji T.

    2011-01-01

    Infection with human immunodeficiency virus type 2 (HIV-2) occurs mainly in West Africa, but an increasing number of cases have been recognized in Europe, India, and the United States. In this era of global integration, clinicians must be aware of when to consider the diagnosis of HIV-2 infection and how to test for this virus. Although there is debate regarding when therapy should be initiated and which regimen should be chosen, recent trials have provided important information on treatment options for HIV-2 infection. In this review, we present information on recent clinical advances in our understanding of HIV-2 infection and highlight remaining diagnostic and therapeutic challenges. PMID:21367732

  9. 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

  10. Simian Immunodeficiency Virus SIVagm Dynamics in African Green Monkeys▿

    PubMed Central

    Pandrea, Ivona; Ribeiro, Ruy M.; Gautam, Rajeev; Gaufin, Thaidra; Pattison, Melissa; Barnes, Mary; Monjure, Christopher; Stoulig, Crystal; Dufour, Jason; Cyprian, Wayne; Silvestri, Guido; Miller, Michael D.; Perelson, Alan S.; Apetrei, Cristian

    2008-01-01

    The mechanisms underlying the lack of disease progression in natural simian immunodeficiency virus (SIV) hosts are still poorly understood. To test the hypothesis that SIV-infected African green monkeys (AGMs) avoid AIDS due to virus replication occurring in long-lived infected cells, we infected six animals with SIVagm and treated them with potent antiretroviral therapy [ART; 9-R-(2-phosphonomethoxypropyl) adenine (tenofovir) and beta-2,3-dideoxy-3-thia-5-fluorocytidine (emtricitabine)]. All AGMs showed a rapid decay of plasma viremia that became undetectable 36 h after ART initiation. A significant decrease of viral load was observed in peripheral blood mononuclear cells and intestine. Mathematical modeling of viremia decay post-ART indicates a half-life of productively infected cells ranging from 4 to 9.5 h, i.e., faster than previously reported for human immunodeficiency virus and SIV. ART induced a slight but significant increase in peripheral CD4+ T-cell counts but no significant changes in CD4+ T-cell levels in lymph nodes and intestine. Similarly, ART did not significantly change the levels of cell proliferation, activation, and apoptosis, already low in AGMs chronically infected with SIVagm. Collectively, these results indicate that, in SIVagm-infected AGMs, the bulk of virus replication is sustained by short-lived cells; therefore, differences in disease outcome between SIVmac infection of macaques and SIVagm infection of AGMs are unlikely due to intrinsic differences in the in vivo cytopathicities between the two viruses. PMID:18216122

  11. 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

    ... Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) through Solid Organ Transplantation'' (76 FR 58517). Written and electronic comments were to be received on or before November 21, 2011... Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus...

  12. 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

  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. 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

  15. 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

  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. NMR structure of the myristylated feline immunodeficiency virus matrix protein.

    PubMed

    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

    2015-05-01

    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

  18. 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

  19. [Pulmonary complications in children with human immunodeficiency virus infection].

    PubMed

    Brockmann V, Pablo; Viviani S, Támara; Peña D, Anamaría

    2007-08-01

    Pulmonary complications in children infected by human immunodeficiency virus (HIV) are common and may be the first manifestation of acquired immunodeficiency syndrome (AIDS). The aim of our study was to review pulmonary diseases and complications in pediatric patients with HIV infection in a large tertiary hospital in Santiago, Chile. We performed a retrospective, descriptive analysis of 17 patients with HIV infection controlled at the Hospital Dr. Sótero del Rio. Respiratory complications/diseases were: overall pneumonia (n: 14), recurrent pneumonia (n: 10), citomegalovirus associated pneumonia (n: 4), Pneumocystis jiroveci associated pneumonia (n: 1) pulmonary tuberculosis (n: 1), lymphoid interstitial pneumonia (n: 3) and chronic pulmonary disease (n: 7). Microorganisms isolated were mostly atypical and frequently associated with severe and chronic pulmonary damage. A high degree of suspicion is required to detect atypical microorganisms promptly, in order to rapidly implement pathogen targeted therapy that could potentially decrease the possibility of sequelae. PMID:17728918

  20. 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

  1. Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients

    PubMed Central

    Alvarez-Muñoz, Ma Teresa; Maldonado-Rodriguez, Angelica; Rojas-Montes, Othon; Torres-Ibarra, Rocio; Gutierrez-Escolano, Fernanda; Vazquez-Rosales, Guillermo; Gomez, Alejandro; Muñoz, Onofre; Torres, Javier; Lira, Rosalia

    2014-01-01

    AIM: To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico. METHODS: We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson’s χ2 and/or Fisher’s exact test. RESULTS: We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05). CONCLUSION: The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV. PMID:25309083

  2. 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. PMID:10945301

  3. Absence of infectious human immunodeficiency virus type 1 in "natural" eccrine sweat.

    PubMed

    Wormser, G P; Bittker, S; Forseter, G; Hewlett, I K; Argani, I; Joshi, B; Epstein, J S; Bucher, D

    1992-01-01

    Although human immunodeficiency virus type 1 (HIV-1) has been found in numerous body fluids, there are no reports of attempts to demonstrate this virus in eccrine sweat, a fluid frequently encountered during person-to-person interactions. "Natural" eccrine sweat samples and blood from 50 HIV-1-seropositive patients and 2 HIV-1-seronegative controls were cultured for HIV-1 by a cocultivation method. Polymerase chain reaction for HIV-1 RNA and proviral DNA was done on 40 sweat samples (39 patients, 1 control). HIV-1 was isolated from peripheral blood mononuclear cells of 39 (78%) of 50 patients but from none of 52 sweat samples. No HIV-1 viral DNA or RNA was detected in the 40 sweat samples tested. With present methodology, infectious HIV-1 cannot be demonstrated in "natural" eccrine sweat samples from HIV-infected patients. PMID:1345794

  4. Properties of human immunodeficiency virus type 1 reverse transcriptase recombination upon infection.

    PubMed

    Sakuragi, Sayuri; Shioda, Tatsuo; Sakuragi, Jun-ichi

    2015-11-01

    Reverse transcription (RT) is one of the hallmark features of retroviruses. During RT, virus encoded reverse transcriptase (RTase) must transfer from one end to the other end of the viral genome on two separate occasions to complete RT and move on to the production of proviral DNA. In addition, multiple strand-transfer events between homologous regions of the dimerized viral genome by RTase are also observed, and such recombination events serve as one of the driving forces behind human immunodeficiency virus (HIV) genome sequence diversity. Although retroviral recombination is widely considered to be important, several features of its mechanism are still unclear. We constructed an HIV-1 vector system to examine the target sequences required for virus recombination, and elucidated other necessary prerequisites to harbor recombination, such as the length, homology and the stability of neighbouring structures around the target sequences. PMID:26282329

  5. 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.

  6. A rare case of verrucous carcinoma of penis in an human immunodeficiency virus- infected patient

    PubMed Central

    Noronha, Tonita Mariola; Girisha, Banavasi S.; Bhat, Shubha P.; Christy, Carol M.; Handattu, Sripathi; Fernandes, Michelle S.

    2015-01-01

    Cancer is a significant cause of morbidity and mortality in human immunodeficiency virus-infected subjects. Verrucous carcinoma is a peculiarly slow evolving, but relentlessly expanding variant of epidermoid carcinoma that is extremely reluctant to metastasize. A 60-year-old unmarried male patient presented with urethral discharge of 3 weeks duration. Dorsal slit of the prepuce revealed an ulceroproliferative growth measuring 3 cm × 3 cm arising from prepuce and involving glans. Biopsy from the growth in the prepuce showed histopathological features of verrucous carcinoma. Partial amputation of the penis was done. Human papillomavirus DNA by polymerase chain reaction was negative. The patient was started on antiretroviral therapy. PMID:26692616

  7. 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

  8. 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

  9. 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

  10. Human Immunodeficiency Virus Infection: The Spectrum Beyond AIDS

    PubMed Central

    Willoughby, Brain C.

    1987-01-01

    Since 1981, the Acquired Immune Deficiency Syndrome (AIDS) has emerged as the major infectious epidemic of our time. It is the most profound manifestation of infection with the Human Immunodeficiency Virus (HIV). Since 1984, serologic methods have existed to detect antibody to HIV. Several other clinical entities have been detected and are attributable to HIV infection. Appropriate counsel must accompany antibody testing. The author discusses the acute seroconversion event, as well as asymptomatic carrier status, including generalized lymphadenopathy. He also reviews the symptomatic states that do not meet the surveillance definition of AIDS, including treatments where available. PMID:21263801

  11. Early diagnosis and testing for human immunodeficiency virus.

    PubMed

    Hesman, Amanda

    2016-06-01

    Human immunodeficiency virus (HIV) is now considered a long-term condition. However, HIV can only become a long-term condition if it is diagnosed early and antiretroviral therapy is commenced immediately. Individuals with HIV who are diagnosed late have an increased risk of death in the year after diagnosis compared to those diagnosed promptly. This article outlines HIV testing policy in the UK, the importance of the early diagnosis of HIV, the barriers to HIV testing, and how to offer testing in a range of settings. PMID:27286626

  12. 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

  13. Care of the Human Immunodeficiency Virus-Infected Menopausal Woman

    PubMed Central

    Cejtin, Helen E.

    2012-01-01

    More women than ever before are both Human Immunodeficiency Virus-infected and menopausal, because of increased survival and more frequent diagnosis in older women. Such a woman has the combined burden of her infection, its treatment, comorbid conditions, and aging. Thus she is at risk for a variety of problems such as disorders of bone mineral density and deficiencies in cognitive functioning. In addition to this, she experiences menopause in a unique fashion, with more symptoms and perhaps at an earlier age. The clinician caring for her must take a proactive approach to this multitude of factors that may affect her health and well-being. PMID:22284959

  14. 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 resistance genotype assay. 866.3950 Section 866.3950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay....

  15. 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 resistance genotype assay. 866.3950 Section 866.3950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay....

  16. 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 resistance genotype assay. 866.3950 Section 866.3950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay....

  17. 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 resistance genotype assay. 866.3950 Section 866.3950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay....

  18. 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 resistance genotype assay. 866.3950 Section 866.3950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay....

  19. 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

  20. 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.

  1. 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.

  2. Feline immunodeficiency virus (FIV) in wild Pallas' cats.

    PubMed

    Brown, Meredith A; Munkhtsog, Bariushaa; Troyer, Jennifer L; Ross, Steve; Sellers, Rani; Fine, Amanda E; Swanson, William F; Roelke, Melody E; O'Brien, Stephen J

    2010-03-15

    Feline immunodeficiency virus (FIV), a feline lentivirus related to HIV, causes immune dysfunction in domestic and wild cats. The Pallas' cat is the only species from Asia known to harbor a species-specific strain of FIV designated FIV(Oma) in natural populations. Here, a 25% seroprevalence of FIV is reported from 28 wild Mongolian Pallas' cats sampled from 2000 to 2008. Phylogenetic analysis of proviral RT-Pol from eight FIV(Oma) isolates from Mongolia, Russia, China and Kazakhstan reveals a unique monophyletic lineage of the virus within the Pallas' cat population, most closely related to the African cheetah and leopard FIV strains. Histopathological examination of lymph node and spleen from infected and uninfected Pallas' cats suggests that FIV(Oma) causes immune depletion in its' native host. PMID:19926144

  3. Cellular Localization of Simian Immunodeficiency Virus in Lymphoid Tissues

    PubMed Central

    Ringler, D. J.; Wyand, M. S.; Walsh, D. G.; MacKey, J. J.; Chalifoux, L. V.; Popovic, M.; Minassian, A. A.; Sehgal, P. K.; Daniel, M. D.; Desrosiers, R. C.; King, N. W.

    1989-01-01

    Simian immunodeficiency virus (SIV) is a lentivirus with genetic relatedness to the human immunodeficiency viruses (HIV-1 and HIV-2). It induces a fatal syndrome in rhesus monkeys that closely parallels the clinical course of AIDS in humans. The authors used double-labeling immunohistochemical procedures on rhesus lymph node and spleen taken during different time periods after SIV infection to localize the p27 gag protein to specific cellular immunophenotypes. In animals with follicular hyperplasia, viral protein was found associated predominantly with follicular dendritic cells. Many of these cells showed ultrastructural alterations consisting of swollen dendritic processes contaning electron-dense material. Lentiviral particles were found associated with this cell type only rarely. In lymphoid tissues with other histopathologic changes, macrophages and multinucleate giant cells were the predominant cell types containing detectable quantities of viral protein; smaller numbers of p27+ lymhocytes were present. Ultrastructurally, viral particles were found within the extracellular spce adjacent to tissue macrophages and within membrane-bound vacuoles of giant cells and tissue macrophage. These results show that certain histologic patterns seen during the course of infection correlate with the localization of viral antigen to specific cellular immunophenotypes and that during the disease course, viral protein is preferentially localized in sections of lymphonode and spleen to cells of the macrophage and dendritic cell lineage. ImagesFigure 1Figure 2Figure 3A, B PMID:2537016

  4. 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

  5. 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. PMID:26174574

  6. 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.

  7. 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

  8. 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

  9. 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...

  10. 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

  11. 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

  12. 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

  13. Oral Manifestations of Human Immunodeficiency Virus-Infected Patients

    PubMed Central

    Pakfetrat, Atessa; Falaki, Farnaz; Delavarian, Zahra; Dalirsani, Zohreh; Sanatkhani, Majid; Zabihi Marani, Mahsa

    2015-01-01

    Introduction: Oral lesions are among the earliest clinical manifestations of human immunodeficiency (HIV) infection and are important in early diagnosis and for monitoring the progression to acquired immunodeficiency syndrome (AIDS). The purpose of this study was to determine the prevalence of oral lesions and their relationship with a number of factors in HIV/AIDS patients attending an HIV center. Materials and Methods: A total of 110 HIV-positive patients were examined to investigate the prevalence of oral lesions according to the criteria established by the European Community Clearing House on Oral Problems Related to HIV Infection. An independent T-test was used for correlation of oral lesions with CD4+ count and a χ2 test was used for analysis of the relationship of co-infection with hepatitis B virus (HBV), sexual contact, route of transmission, history of drug abuse, and history of incarceration. Results: Most of the cases were male patients (82.7%). The mean age across all participants was 36.2±8.1 years. Rampant carries, severe periodontitis and oral candidiasis were the most notable oral lesions. Oral lesions were more prevalent in patients between 26–35 years of age. There was a significant difference between patients with and without pseudomembranous candidiasis and angular cheilitis according to mean level of CD4+. Conclusion: The most common oral presentations were severe periodontitis, pseudomembranous candidiasis and xerostomia. PMID:25745611

  14. Pneumocystis jirovecii Pneumonia in Human Immunodeficiency Virus Infection.

    PubMed

    Siegel, Marc; Masur, Henry; Kovacs, Joseph

    2016-04-01

    The presentation of Pneumocystis pneumonia (PCP) in previously healthy men having sex with men (MSM) in San Francisco and New York City in 1981 heralded the beginning of the human immunodeficiency virus (HIV) pandemic. Despite a decreasing incidence of PCP among patients with HIV/AIDS (acquired immunodeficiency syndrome) since the advent of combination antiretroviral therapy in the mid-1990s, PCP remains one of the most common AIDS-defining opportunistic infections in the United States and Western Europe. Newer molecular diagnostic tests in conjunction with standard immunofluorescent or colorimetric tests have allowed for more rapid and accurate diagnosis. Although several effective oral and intravenous therapies exist to treat PCP, mortality rates in HIV-infected individuals remain unacceptably high, especially in those with advanced AIDS. The identification of specific mutations in Pneumocystis genes targeted by trimethoprim-sulfamethoxazole has raised concerns about the development of resistance to the drug of choice and may ultimately lead to greater utilization of alternative therapies to treat PCP in the future. PMID:26974301

  15. Oral lesions in infection with human immunodeficiency virus.

    PubMed

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

    2005-09-01

    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

  16. The Effects of a Kansas Education Class on Students' Knowledge and Attitudes of Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome.

    ERIC Educational Resources Information Center

    Sager, R. Warren, Jr.

    This study was undertaken to investigate the knowledge and attitudes of 8th, 9th, and 10th grade Kansas students pertaining to human immunodeficiency virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS). Attitudes and knowledge of 9th and 10th grade students who had participated in a Sex Respect Class offered in the 9th grade were compared…

  17. Human Immunodeficiency Virus gag and protease: partners in resistance

    PubMed Central

    2012-01-01

    Human Immunodeficiency Virus (HIV) maturation plays an essential role in the viral life cycle by enabling the generation of mature infectious virus particles through proteolytic processing of the viral Gag and GagPol precursor proteins. An impaired polyprotein processing results in the production of non-infectious virus particles. Consequently, particle maturation is an excellent drug target as exemplified by inhibitors specifically targeting the viral protease (protease inhibitors; PIs) and the experimental class of maturation inhibitors that target the precursor Gag and GagPol polyproteins. Considering the different target sites of the two drug classes, direct cross-resistance may seem unlikely. However, coevolution of protease and its substrate Gag during PI exposure has been observed both in vivo and in vitro. This review addresses in detail all mutations in Gag that are selected under PI pressure. We evaluate how polymorphisms and mutations in Gag affect PI therapy, an aspect of PI resistance that is currently not included in standard genotypic PI resistance testing. In addition, we consider the consequences of Gag mutations for the development and positioning of future maturation inhibitors. PMID:22867298

  18. Inhibition of human immunodeficiency virus type-1 by cdk inhibitors.

    PubMed

    Guendel, Irene; Agbottah, Emmanuel T; Kehn-Hall, Kylene; Kashanchi, Fatah

    2010-01-01

    Current therapy for human immunodeficiency virus (HIV-1) infection relies primarily on the administration of anti-retroviral nucleoside analogues, either alone or in combination with HIV-protease inhibitors. Although these drugs have a clinical benefit, continuous therapy with the drugs leads to drug-resistant strains of the virus. Recently, significant progress has been made towards the development of natural and synthetic agents that can directly inhibit HIV-1 replication or its essential enzymes. We previously reported on the pharmacological cyclin-dependent kinase inhibitor (PCI) r-roscovitine as a potential inhibitor of HIV-1 replication. PCIs are among the most promising novel antiviral agents to emerge over the past few years. Potent activity on viral replication combined with proliferation inhibition without the emergence of resistant viruses, which are normally observed in HAART patients; make PCIs ideal candidates for HIV-1 inhibition. To this end we evaluated twenty four cdk inhibitors for their effect on HIV-1 replication in vitro. Screening of these compounds identified alsterpaullone as the most potent inhibitor of HIV-1 with activity at 150 nM. We found that alsterpaullone effectively inhibits cdk2 activity in HIV-1 infected cells with a low IC50 compared to control uninfected cells. The effects of alsterpaullone were associated with suppression of cdk2 and cyclin expression. Combining both alsterpaullone and r-roscovitine (cyc202) in treatment exhibited even stronger inhibitory activities in HIV-1 infected PBMCs. PMID:20334651

  19. 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

  20. 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

  1. Overview of Microbicides for the prevention of human immunodeficiency virus

    PubMed Central

    Abdool Karim, Salim S.; Baxter, Cheryl

    2012-01-01

    Human immunodeficiency virus (HIV) prevention tools that women can use and control are urgently needed. Microbicides are chemical products applied to the vagina or rectum to prevent the sexual transmission of HIV. Four classes of candidate microbicides have been tested to date: those that (1) enhance the natural defences in the vagina to inactivate HIV; (2) inactivate HIV in the vagina; (3) prevent HIV from attaching to, and fusing with, the host cells; and (4) prevent HIV from replicating in genital tract host cells. Despite numerous disappointing efficacy trial results over the past 20 years, substantial progress is now being made in microbicide development after the release of the CAPRISA 004 trial, which provided proof-of-concept that topical antiretroviral microbicides can prevent sexual transmission of HIV and herpes simplex type-2 infection. Microbicides, which fill an important gap for women-controlled prevention methods, have the potential to alter the course of the HIV pandemic. PMID:22386823

  2. Fungal, Viral, and Parasitic Pneumonias Associated with Human Immunodeficiency Virus.

    PubMed

    Skalski, Joseph H; Limper, Andrew H

    2016-04-01

    Respiratory illness is an important cause of morbidity and mortality in patients with human immunodeficiency virus (HIV). The spectrum of pulmonary disease that can affect patients with HIV is wide and includes opportunistic infection with many fungal, viral, and parasitic organisms. This article reviews the clinical presentation; approach to diagnosis; and management of fungal, viral, and parasitic pneumonias that can develop in patients with HIV including respiratory disease caused by Aspergillus, Cryptococcus, Histoplasma, Coccidioides, Cytomegalovirus, Toxoplasma, and Strongyloides. Because clinical symptoms and radiographic patterns are often insensitive at distinguishing these pulmonary infections, this review particularly focuses on specific host risk factors and diagnostic testing to consider when approaching HIV patients with respiratory illness. PMID:26974302

  3. 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

  4. 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

  5. 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

  6. Coronary Artery Disease in the Human Immunodeficiency Virus Seropositive Population.

    PubMed

    Barakat, Michael G; Arora, Rohit R

    2016-01-01

    The development of efficient combined antiretroviral therapies has lengthened the mean life span of the population affected with human immunodeficiency virus (HIV) transforming this terminal infection to a chronic yet manageable disease. Nonetheless, patients with HIV--treatment naive or not--exhibit larger risks for coronary artery disease than the noninfected population. Moreover, coronary atherosclerosis/arteriosclerosis may be the most prevalent condition in the HIV-infected population that is being accentuated by the effects of viral agents and the antiretroviral drugs, especially protease inhibitors. Nonetheless, generalized metabolic dysfunctions and premature senescence are often attributed to the viremia caused by the HIV infection directly and primarily. Therefore, a multifactorial approach is to be considered when attempting to explain the strong correlation between HIV and coronary artery disease, including co-opportunistic viremias and vitamin D insufficiency/deficiency. PMID:23797758

  7. Pathogenesis and treatment of human immunodeficiency virus lipodystrophy

    PubMed Central

    Jain, Suyog Subhash; Ramteke, Karuna Balwant; Raparti, Girish Tulsidas; Kalra, Sanjay

    2012-01-01

    Enhanced understanding about the way human immunodeficiency virus (HIV) infects and causes infection in humans has led to invention and use of newer more effective antiretroviral drugs. As treatment for HIV is long term, side effects of the antiretrovirals become an important area of research focus. Antiretrovirals can cause severe metabolic abnormalities, collectively known as HIV lipodystrophy syndrome. If untreated, these metabolic abnormalities have the potential to increase stroke and cardiac ischemia. Management includes choice of nonoffending drugs, switch over to less toxic drugs, hypolipidemics, oral antidiabetics including thiazolidinediones, metformin and growth hormone analogs and finally facial surgeries. Updated knowledge about HIV lipodystrophy, and the hormone-related drugs used to treat it, is essential for physicians and endocrinologists to be able to diagnose the patients and effectively treat them. PMID:22701839

  8. Impact of Mucosal Inflammation on Oral Simian Immunodeficiency Virus Transmission

    PubMed Central

    Chen, Hui-Ling; Hodara, Vida L.; Chu, Lianrui; Parodi, Laura M.; Smith, Lisa M.; Sexton, Valerie; Cappelli, David; Sodora, Donald L.

    2013-01-01

    Mucosal tissues are the primary route of transmission for most respiratory and sexually transmitted diseases, including human immunodeficiency virus (HIV). There is epidemiological evidence that genital mucosal inflammation leads to enhanced HIV type 1 (HIV-1) transmission. The objective of this study was to assess the influence of periodontal inflammation on oral HIV transmission using a nonhuman primate model of teeth ligature-induced periodontitis. Simian immunodeficiency virus (SIV) was nontraumatically applied to the gingiva after moderate gingivitis was identified through clinical and immunologic analyses (presence of inflammatory cytokines). Overall oral SIV infection rates were similar in the gingivitis-induced and control groups (5 infections following 12 SIV administrations for each), although more macaques were infected with multiple viral variants in the gingivitis group. SIV infection also affected the levels of antiviral and inflammatory cytokines in the gingival crevicular fluid, and a synergistic effect was observed, with alpha interferon and interferon-inducible protein 10 undergoing significant elevations following SIV infection in macaques with gingivitis compared to controls. These increases in antiviral and inflammatory immune modulators in the SIV-infected gingivitis macaques could also be observed in blood plasma, although the effects at both compartments were generally restricted to the acute phase of the infection. In conclusion, while moderate gingivitis was not associated with increased susceptibility to oral SIV infection, it resulted in elevated levels of cytokines in the oral mucosa and plasma of the SIV-infected macaques. These findings suggest a synergy between mucosal inflammation and SIV infection, creating an immune milieu that impacts the early stages of the SIV infection with potential implications for long-term pathogenesis. PMID:23175379

  9. 75 FR 22814 - Guidance for Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    ... (70 FR 43439), FDA announced the availability of the draft guidance of the same title. FDA received...: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV... Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV): Testing, Product Disposition, and Donor...

  10. CD8+ T cells maintain suppression of simian immunodeficiency virus in the central nervous system.

    PubMed

    Marcondes, Maria Cecilia G; Morsey, Brenda; Emanuel, Katy; Lamberty, Benjamin G; Flynn, Claudia T; Fox, Howard S

    2015-01-01

    Human immunodeficiency virus (HIV) accesses the brain early in infection and can lead to neurocognitive disorders. The brain can also serve as a viral reservoir, but how virus is controlled in the brain is unknown. To examine this, CD8-depleting monoclonal antibody was injected into the cerebrospinal fluid of rhesus monkeys with chronic simian immunodeficiency virus (SIV) infection. This treatment led to the rapid increase of SIV in the brain. Virus in the brain is maintained by active suppression from the host immune system. This dynamic interaction can be manipulated in efforts to control and eradicate virus from the brain and other reservoirs. PMID:25035516

  11. Pathogenesis of simian immunodeficiency virus encephalitis: viral determinants of neurovirulence.

    PubMed Central

    Mankowski, J L; Flaherty, M T; Spelman, J P; Hauer, D A; Didier, P J; Amedee, A M; Murphey-Corb, M; Kirstein, L M; Muñoz, A; Clements, J E; Zink, M C

    1997-01-01

    To examine the relationship between macrophage tropism and neurovirulence, macaques were inoculated with two recombinant hybrid viruses derived from the parent viruses SIVmac239, a lymphocyte-tropic, non-neurovirulent clone, and SIV/17E-Br, a macrophage-tropic, neurovirulent virus strain. The first recombinant, SIV/17E-Cl, contained the portion of the env gene that encodes the surface glycoprotein and a short segment of the transmembrane glycoprotein of SIV/17E-Br in the backbone of SIVmac239. Unlike SIVmac239, SIV/17E-Cl replicated productively in macrophages, demonstrating that sequences in the surface portion of env determine macrophage tropism. None of five macaques inoculated with SIV/17E-Cl developed simian immunodeficiency virus (SIV) encephalitis. The second recombinant, SIV/17E-Fr, which contained the entire env and nef genes and the 3' long terminal repeat of SIV/17E-Br in the SIVmac239 backbone, was also macrophage tropic. Six of nine macaques inoculated with SIV/17E-Fr developed SIV encephalitis ranging from mild to moderate in severity, indicating a significant (P = 0.031) difference in the neurovirulence of the two recombinants. In both groups of macaques, CD4+ cell counts declined gradually during infection and there was no significant difference in the rate of the decline between the two groups of macaques. This study demonstrated that macrophage tropism alone is not sufficient for the development of neurological disease. In addition, it showed that while sequences in the surface portion of the envelope gene determine macrophage tropism, additional sequences derived from the transmembrane portion of envelope and/or nef confer neurovirulence. PMID:9223498

  12. 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

  13. 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

  14. Expression and coreceptor function of APJ for primate immunodeficiency viruses.

    PubMed

    Puffer, B A; Sharron, M; Coughlan, C M; Baribaud, F; McManus, C M; Lee, B; David, J; Price, K; Horuk, R; Tsang, M; Doms, R W

    2000-10-25

    APJ is a seven transmembrane domain G-protein-coupled receptor that functions as a coreceptor for some primate immunodeficiency virus strains. The in vivo significance of APJ coreceptor function remains to be elucidated, however, due to the lack of an antibody that can be used to assess APJ expression, and because of the absence of an antibody or ligand that can block APJ coreceptor activity. Therefore, we produced a specific monoclonal antibody (MAb 856) to APJ and found that it detected this receptor in FACS, immunofluorescence, and immunohistochemistry studies. MAb 856 also recognized APJ by Western blot, enabling us to determine that APJ is N-glycosylated. Using this antibody, we correlated APJ expression with coreceptor activity and found that APJ had coreceptor function even at low levels of expression. However, we found that APJ could not be detected by FACS analysis on cell lines commonly used to propagate primate lentiviruses, nor was it expressed on human PBMC cultured under a variety of conditions. We also found that some viral envelope proteins could mediate fusion with APJ-positive, CD4-negative cells, provided that CD4 was added in trans. These findings indicate that in some situations APJ use could render primary cell types susceptible to virus infection, although we have not found any evidence that this occurs. Finally, the peptide ligand for APJ, apelin-13, efficiently blocked APJ coreceptor activity. PMID:11040134

  15. Genotypic Testing for Human Immunodeficiency Virus Type 1 Drug Resistance

    PubMed Central

    Shafer, Robert W.

    2002-01-01

    There are 16 approved human immunodeficiency virus type 1 (HIV-1) drugs belonging to three mechanistic classes: protease inhibitors, nucleoside and nucleotide reverse transcriptase (RT) inhibitors, and nonnucleoside RT inhibitors. HIV-1 resistance to these drugs is caused by mutations in the protease and RT enzymes, the molecular targets of these drugs. Drug resistance mutations arise most often in treated individuals, resulting from selective drug pressure in the presence of incompletely suppressed virus replication. HIV-1 isolates with drug resistance mutations, however, may also be transmitted to newly infected individuals. Three expert panels have recommended that HIV-1 protease and RT susceptibility testing should be used to help select HIV drug therapy. Although genotypic testing is more complex than typical antimicrobial susceptibility tests, there is a rich literature supporting the prognostic value of HIV-1 protease and RT mutations. This review describes the genetic mechanisms of HIV-1 drug resistance and summarizes published data linking individual RT and protease mutations to in vitro and in vivo resistance to the currently available HIV drugs. PMID:11932232

  16. Human Immunodeficiency Virus and Liver Disease Forum 2012

    PubMed Central

    Sherman, Kenneth E.; Thomas, David; Chung, Raymond T.

    2013-01-01

    In the U.S. more than 1.1 million individuals are infected with the human immunodeficiency virus (HIV). These patients exhibit a high frequency of coinfections with other hepatotropic viruses and ongoing fibrosis leading to cirrhosis and liver-related mortality. The etiologies of liver disease include viral hepatitis coinfections, drug-related hepatotoxicity, fatty liver disease, and direct and indirect effects from HIV infection including increased bacterial translocation, immune activation, and presence of soluble proteins that modulate the hepatic cytokine environment. New treatments for HCV using direct acting agents appear viable, though issues related to intrinsic toxicities and drug:drug interactions remain. Recent research suggests that acute HCV infection, unrecognized hepatitis D infection, and hepatitis E may all represent emergent areas of concern. Antiretroviral agents, including those used in past years may represent risk factors for hepatic injury and portal hypertension. Key issues in the future include systematic implementation of liver disease management and new treatment in HIV-infected populations with concomitant injection drug use, alcohol use, and low socioeconomic status. PMID:23904401

  17. 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

  18. The epidemiology of human immunodeficiency virus in South Africa.

    PubMed Central

    Williams, B G; Gouws, E

    2001-01-01

    We review the epidemiology of human immunodeficiency virus (HIV) in South Africa where the prevalence of HIV infection is among the highest in the world. The epidemic reached South Africa relatively recently but the prevalence of infection has increased rapidly and there are significant differences among provinces. Although few 15-year-old people are infected the prevalence increases rapidly with age thereafter, especially among women. The prevalence of herpes simplex virus type 2 exceeds that of HIV and curable sexually transmitted infections are common. 'Circular migration' may help to explain the high rates and rapid spread of HIV in the region. The incidence of tuberculosis has increased dramatically as a result of the HIV epidemic. Antiretroviral therapy for the prevention of vertical transmission has been shown to be effective in local conditions but transmission through breast-feeding remains problematical. While some epidemiological models have been developed, much more needs to be done in this regard in order to plan, coordinate and evaluate an effective response to the epidemic. We conclude by discussing some of the research that is needed and steps that could be taken to reduce the continued spread of the infection. PMID:11516385

  19. 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

  20. Human immunodeficiency virus type 1 preintegration complexes containing discontinuous plus strands are competent to integrate in vitro.

    PubMed Central

    Miller, M D; Wang, B; Bushman, F D

    1995-01-01

    Despite intensive study, the mechanism by which many retroviruses complete reverse transcription has remained unclear. Most retroviruses and all lentiviruses fail to synthesize a full-length second strand of the viral cDNA (plus strand) efficiently in infected cells. For human immunodeficiency virus type 1, we find in synchronous infection experiments that full-length plus strands are rare (< 1% of products) at times when integration is likely taking place. Subviral nucleoprotein complexes containing such discontinuous cDNA can be extracted from infected cells and used to generate integration products in vitro. Analysis of such integration products using two-dimensional gel electrophoresis revealed that the discontinuous viral DNA was efficiently integrated into an added target DNA. These data support a model in which the discontinuities in the plus strand need not be sealed until after integration, potentially by the enzymes that are already thought to repair DNA gaps at the junctions between host and viral DNA. PMID:7745750

  1. Efficiency of Cell-Free and Cell-Associated Virus in Mucosal Transmission of Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus

    PubMed Central

    Hulot, Sandrine L.; Korioth-Schmitz, Birgit; Gombos, Randi B.; Zheng, Yi; Owuor, Joshua; Lifton, Michelle A.; Ayeni, Christian; Najarian, Robert M.; Yeh, Wendy W.; Asmal, Mohammed; Zamir, Gideon; Letvin, Norman L.

    2013-01-01

    Effective strategies are needed to block mucosal transmission of human immunodeficiency virus type 1 (HIV-1). Here, we address a crucial question in HIV-1 pathogenesis: whether infected donor mononuclear cells or cell-free virus plays the more important role in initiating mucosal infection by HIV-1. This distinction is critical, as effective strategies for blocking cell-free and cell-associated virus transmission may be different. We describe a novel ex vivo model system that utilizes sealed human colonic mucosa explants and demonstrate in both the ex vivo model and in vivo using the rectal challenge model in rhesus monkeys that HIV-1-infected lymphocytes can transmit infection across the mucosa more efficiently than cell-free virus. These findings may have significant implications for our understanding of the pathogenesis of mucosal transmission of HIV-1 and for the development of strategies to prevent HIV-1 transmission. PMID:24109227

  2. Detection of feline immunodeficiency virus in saliva and plasma by cultivation and polymerase chain reaction.

    PubMed Central

    Matteucci, D; Baldinotti, F; Mazzetti, P; Pistello, M; Bandecchi, P; Ghilarducci, R; Poli, A; Tozzini, F; Bendinelli, M

    1993-01-01

    The rates of feline immunodeficiency virus (FIV) isolation from saliva, plasma, and peripheral blood mononuclear cells (PBMC) of infected cats were compared; isolation rates were 18, 14, and 81%, respectively, in naturally infected cats and 25, 57, and 100%, respectively, in experimentally infected animals. There was no obvious relationship between isolation rate and clinical stage or between isolation rate and the titer of neutralizing antibody in serum. Virus could be isolated from one salivary gland as early as 1 week postinfection and, on a more regular basis, starting at 3 weeks postinfection, when, however, most other tissues were also positive. Polymerase chain reaction analysis showed that FIV genomes are present in saliva and plasma more frequently than expected on the basis of isolation data. Saliva was also found to contain viral DNA, indicating that it may harbor virus-infected cells as well as free virus. The addition of plasma but not of saliva to PBMC cultures delayed FIV growth. Isolation from plasma may be hampered by FIV neutralizing antibody and by the cytotoxic activity of this fluid for the PBMC used as a cell substrate. Images PMID:8384624

  3. Polyvalent HIV-1 Env vaccine formulations delivered by the DNA priming plus protein boosting approach are effective in generating neutralizing antibodies against primary human immunodeficiency virus type 1 isolates from subtypes A, B, C, D and E.

    PubMed

    Wang, Shixia; Pal, Ranajit; Mascola, John R; Chou, Te-Hui W; Mboudjeka, Innocent; Shen, Siyuan; Liu, Qin; Whitney, Stephen; Keen, Timothy; Nair, B C; Kalyanaraman, V S; Markham, Philip; Lu, Shan

    2006-06-20

    A major challenge in developing an HIV-1 vaccine is to identify immunogens and their delivery methods that can elicit broad neutralizing antibodies against primary isolates of different genetic subtypes. Recently, we demonstrated that priming with DNA vaccines expressing primary HIV-1 envelope glycoprotein (Env) followed by recombinant Env protein boosting was successful in generating positive neutralizing antibody responses against a clade B primary HIV-1 isolate, JR-FL, that was not easily neutralized. In the current study, we examined whether the DNA priming plus recombinant protein boosting approach delivering a polyvalent primary Env formulation was able to generate neutralizing antibodies against primary HIV-1 viral isolates from various genetic subtypes. New Zealand White rabbits were first immunized with DNA vaccines expressing one, three or eight primary HIV-1 gp120 antigens delivered by a gene gun followed by recombinant gp120 protein boosting. Neutralizing antibody responses were examined by two independently executed neutralization assays: the first one was a single round infection neutralization assay against a panel of 10 primary HIV-1 isolates of subtypes A, B, C and E and the second one used the PhenoSense assay against a panel of 12 pseudovirues expressing primary HIV-1 Env antigens from subtypes A, B, C, D and E as well as 2 pseudoviruses expressing the Env antigens from MN and NL4-3 viruses. Rabbit sera immunized with the DNA priming plus protein boosting approach, but not DNA vaccine alone or Env protein alone, were capable of neutralizing 7 of 10 viruses in the first assay and 12 of 14 viruses in the second assay. More importantly, sera immunized with the polyvalent Env antigens were able to neutralize a significantly higher percentage of viruses than the sera immunized with the monovalent antigens. Our results suggest that DNA priming followed by recombinant Env protein boosting can be used to deliver polyvalent Env-antigen-based HIV-1

  4. Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals, improved with anti-human herpes virus treatment

    PubMed Central

    Klínger Hernández, Julio César; Niño Castaño, Victoria Eugenia

    2012-01-01

    Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immunodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lymphocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diagnosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings' health. PMID:24893304

  5. 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

  6. 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

  7. Intestinal Epithelial Barrier Disruption through Altered Mucosal MicroRNA Expression in Human Immunodeficiency Virus and Simian Immunodeficiency Virus Infections

    PubMed Central

    Gaulke, Christopher A.; Porter, Matthew; Han, Yan-Hong; Sankaran-Walters, Sumathi; Grishina, Irina; George, Michael D.; Dang, Angeline T.; Ding, Shou-Wei; Jiang, Guochun; Korf, Ian

    2014-01-01

    ABSTRACT Epithelial barrier dysfunction during human immunodeficiency virus (HIV) infection has largely been attributed to the rapid and severe depletion of CD4+ T cells in the gastrointestinal (GI) tract. Although it is known that changes in mucosal gene expression contribute to intestinal enteropathy, the role of small noncoding RNAs, specifically microRNA (miRNA), has not been investigated. Using the simian immunodeficiency virus (SIV)-infected nonhuman primate model of HIV pathogenesis, we investigated the effect of viral infection on miRNA expression in intestinal mucosa. SIV infection led to a striking decrease in the expression of mucosal miRNA compared to that in uninfected controls. This decrease coincided with an increase in 5′-3′-exoribonuclease 2 protein and alterations in DICER1 and Argonaute 2 expression. Targets of depleted miRNA belonged to molecular pathways involved in epithelial proliferation, differentiation, and immune response. Decreased expression of several miRNA involved in maintaining epithelial homeostasis in the gut was localized to the proliferative crypt region of the intestinal epithelium. Our findings suggest that SIV-induced decreased expression of miRNA involved in epithelial homeostasis, disrupted expression of miRNA biogenesis machinery, and increased expression of XRN2 are involved in the development of epithelial barrier dysfunction and gastroenteropathy. IMPORTANCE MicroRNA (miRNA) regulate the development and function of intestinal epithelial cells, and many viruses disrupt normal host miRNA expression. In this study, we demonstrate that SIV and HIV disrupt expression of miRNA in the small intestine during infection. The depletion of several key miRNA is localized to the proliferative crypt region of the gut epithelium. These miRNA are known to control expression of genes involved in inflammation, cell death, and epithelial maturation. Our data indicate that this disruption might be caused by altered expression of mi

  8. Ring finger protein ZIN interacts with human immunodeficiency virus type 1 Vif.

    PubMed

    Feng, Feng; Davis, Adam; Lake, Julie-Anne; Carr, Jill; Xia, Wei; Burrell, Christopher; Li, Peng

    2004-10-01

    Virion infectivity factor (Vif) protein of human immunodeficiency virus type 1 (HIV-1) is essential for the productive infection of primary human CD4 T lymphocytes and macrophages. Vif overcomes the HIV-inhibitory effects of cellular factor APOBEC3G, which has cytidine deaminase activity. We previously reported the isolation of a Vif-interacting ring finger protein, Triad 3, from a human leukocyte cDNA library, using the yeast two-hybrid system. The full-length cellular protein homologue of Triad 3 has been recently identified as the zinc finger protein inhibiting NF-kappaB (ZIN). Sequence analysis indicates that Triad 3 protein contains all four major ring-like motifs of ZIN. We report here that ZIN binds to purified Vif in vitro and that Triad 3/ZIN interacts with HIV-1 Vif in transfected human 293T cells, as demonstrated by coimmunoprecipitation. To test the biological relevance of this interaction, we produced infectious HIV-1 NL4.3 in the presence or absence of cotransfected ZIN. HIV-1 NL4.3 virus stocks produced in the presence of exogenously expressed ZIN were twofold less infectious in a single-cycle infectivity assay than virus produced in the absence of exogenous ZIN. It was further shown that cells infected with HIV NL4.3 virus stocks produced in the presence of exogenously expressed ZIN were impaired in viral DNA synthesis by twofold. The impairment in viral reverse transcription and the reduction in single-cycle viral infectivity were both shown to be dependent on the presence of Vif in the virus producer cells. The possible mechanisms by which ZIN interferes with the early events of HIV-1 replication are discussed. PMID:15367624

  9. Impact of simian immunodeficiency virus infection on chimpanzee population dynamics.

    PubMed

    Rudicell, Rebecca S; Holland Jones, James; Wroblewski, Emily E; Learn, Gerald H; Li, Yingying; Robertson, Joel D; Greengrass, Elizabeth; Grossmann, Falk; Kamenya, Shadrack; Pintea, Lilian; Mjungu, Deus C; Lonsdorf, Elizabeth V; Mosser, Anna; Lehman, Clarence; Collins, D Anthony; Keele, Brandon F; Goodall, Jane; Hahn, Beatrice H; Pusey, Anne E; Wilson, Michael L

    2010-01-01

    Like human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus of chimpanzees (SIVcpz) can cause CD4+ T cell loss and premature death. Here, we used molecular surveillance tools and mathematical modeling to estimate the impact of SIVcpz infection on chimpanzee population dynamics. Habituated (Mitumba and Kasekela) and non-habituated (Kalande) chimpanzees were studied in Gombe National Park, Tanzania. Ape population sizes were determined from demographic records (Mitumba and Kasekela) or individual sightings and genotyping (Kalande), while SIVcpz prevalence rates were monitored using non-invasive methods. Between 2002-2009, the Mitumba and Kasekela communities experienced mean annual growth rates of 1.9% and 2.4%, respectively, while Kalande chimpanzees suffered a significant decline, with a mean growth rate of -6.5% to -7.4%, depending on population estimates. A rapid decline in Kalande was first noted in the 1990s and originally attributed to poaching and reduced food sources. However, between 2002-2009, we found a mean SIVcpz prevalence in Kalande of 46.1%, which was almost four times higher than the prevalence in Mitumba (12.7%) and Kasekela (12.1%). To explore whether SIVcpz contributed to the Kalande decline, we used empirically determined SIVcpz transmission probabilities as well as chimpanzee mortality, mating and migration data to model the effect of viral pathogenicity on chimpanzee population growth. Deterministic calculations indicated that a prevalence of greater than 3.4% would result in negative growth and eventual population extinction, even using conservative mortality estimates. However, stochastic models revealed that in representative populations, SIVcpz, and not its host species, frequently went extinct. High SIVcpz transmission probability and excess mortality reduced population persistence, while intercommunity migration often rescued infected communities, even when immigrating females had a chance of being SIVcpz infected

  10. Reevaluation of possible outcomes of infections with human immunodeficiency virus.

    PubMed

    Tamalet, C; Colson, P; Decroly, E; Dhiver, C; Ravaux, I; Stein, A; Raoult, D

    2016-04-01

    Several lines of evidence indicate that HIV infection can result in several possible incomes, including a very small proportion of individuals whose HIV replication is controlled after treatment interruption (known as HIV posttreatment controllers) or spontaneously without any treatment (known as HIV elite controllers). Both types of individuals are HIV RNA negative but HIV DNA positive, with living virus which can be stimulated ex vivo. A review was conducted to assess the literature on yet rarer cases with detectable integrated HIV DNA without HIV infectious virus in HIV-seropositive or -negative individuals. Three categories of patients were identified: (a) HIV-seropositive individuals with apparent spontaneous cure from their HIV infection, (b) HIV-seronegative children born to HIV-infected mothers and (c) highly exposed seronegative adults. Validity criteria were proposed to assess the presence of integrated HIV DNA as possible or unquestionable in these three categories. Only three articles among the 22 ultimately selected fulfilled these criteria. Among the highly exposed seronegative subjects, some individuals were described as being without integrated HIV DNA, probably because these subjects were not investigated using relevant, highly sensitive methods. Finally, we propose a definition of spontaneous cure of HIV infection based on clinical, immunologic and virologic criteria. PMID:26794031

  11. 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

  12. 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

    ... 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... determine whether the patient is infected with such virus, identified as being a sexual partner of...

  13. 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

    ... 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... determine whether the patient is infected with such virus, identified as being a sexual partner of...

  14. 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... determine whether the patient is infected with such virus, identified as being a sexual partner of...

  15. 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... determine whether the patient is infected with such virus, identified as being a sexual partner of...

  16. 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

    ... 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... determine whether the patient is infected with such virus, identified as being a sexual partner of...

  17. Iatrogenic colorectal Kaposi sarcoma complicating a refractory ulcerative colitis in a human immunodeficiency negative-virus patient.

    PubMed

    Hamzaoui, Lamine; Kilani, Houda; Bouassida, Mahdi; Mahmoudi, Moufida; Chalbi, Emna; Siai, Karima; Ezzine, Heykel; Touinsi, Hassen; Azzouz, Mohamed M'saddak; Sassi, Sadok

    2013-01-01

    Kaposi sarcoma is a mesenchymal tumor associated to a human herpes virus-8. It often occurs in human immunodeficiency virus-positive subjects. Colorectal localization is rare. We report the case of a colorectal Kaposi sarcoma complicating a refractory ulcerative colitis treated with surgery after the failure of immunomodulator therapy in a human immunodeficiency virus-negative heterosexual man. PMID:24396560

  18. Incomplete protection, but suppression of virus burden, elicited by subunit simian immunodeficiency virus vaccines.

    PubMed Central

    Israel, Z R; Edmonson, P F; Maul, D H; O'Neil, S P; Mossman, S P; Thiriart, C; Fabry, L; Van Opstal, O; Bruck, C; Bex, F

    1994-01-01

    We compared the efficacy of immunization with either simian immunodeficiency virus (SIV) Env glycoprotein (Env), Env plus Gag proteins (Gag-Env), or whole inactivated virus (WIV), with or without recombinant live vaccinia vector (VV) priming, in protecting 23 rhesus macaques (six vaccine and two control groups) from challenge with SIVmac251 clone BK28. Vaccination elicited high titers of syncytium-inhibiting and anti-Env (gp120/gp160) antibodies in all vaccinated macaques and anti-Gag (p27) antibodies in groups immunized with WIV or Gag-Env. Only WIV-immunized macaques developed anticell (HuT78) antibodies. After homologous low-dose intravenous virus challenge, we used frequency of virus isolation, provirus burden, and change in antibody titers to define four levels of resistance to SIV infection as follows. (i) No infection ("sterilizing" immunity) was induced only in WIV-immunized animals. (ii) Abortive infection (strong immunity) was defined when virus or provirus were detected early in the postchallenge period but not thereafter and no evidence of virus or provirus was detected in terminal tissues. This response was observed in two animals (one VV-Env and one Gag-Env). (iii) Suppression of infection (incomplete or partial immunity) described a gradient of virus suppression manifested by termination of viremia, declining postchallenge antibody titers, and low levels (composite mean = 9.1 copies per 10(6) cells) of provirus detectable in peripheral blood mononuclear cells or lymphoid tissues at termination (40 weeks postchallenge). This response occurred in the majority (8 of 12) of subunit-vaccinated animals. (iv) Active infection (no immunity) was characterized by persistent virus isolation from blood mononuclear cells, increasing viral antibody titers postchallenge, and high levels (composite mean = 198 copies per 10(6) cells) of provirus in terminal tissues and blood. Active infection developed in all controls and two of three VV-Gag-Env-immunized animals

  19. Persistent infection of chimpanzees with human immunodeficiency virus: serological responses and properties of reisolated viruses.

    PubMed Central

    Nara, P L; Robey, W G; Arthur, L O; Asher, D M; Wolff, A V; Gibbs, C J; Gajdusek, D C; Fischinger, P J

    1987-01-01

    Persistent infection by human immunodeficiency virus (HIV-1) in the chimpanzee may be valuable for immunopathologic and potential vaccine evaluation. Two HIV strains, the tissue culture-derived human T-cell lymphotropic virus type IIIB (HTLV-IIIB) and in vivo serially passaged lymphadenopathy-associated virus type 1 (LAV-1), were injected intravenously into chimpanzees. Two animals received HTLV-IIIB as either virus-infected H9 cells or cell-free virus. A third animal received chimpanzee-passaged LAV-1. Evaluation of their sera for virus-specific serologic changes, including neutralizations, was done during a 2-year period. During this period all animals had persistently high titers of antibodies to viral core and envelope antigens. All three animals developed a progressively increasing type-specific neutralizing LAV-1 versus HTLV-IIIB antibody titer during the 2-year observation period which broadened in specificity to include HTLV-HIRF, HTLV-IIIMN, and HTLV-IIICC after 6 to 12 months. The antibody titers against both viruses were still increasing by 2 years after experimental virus inoculation. Sera from all animals were capable of neutralizing both homologously and heterologously reisolated virus from chimpanzees. A slightly more rapid type-specific neutralizing response was noted for the animal receiving HTLV-IIIB-infected cells compared with that for cell-free HTLV-IIIB. Sera from all persistently infected chimpanzees were capable of mediating group-specific antibody-mediated complement-dependent cytolysis of HIV-infected cells derived from all isolates tested. Viruses reisolated from all three animals at 20 months after inoculation revealed very similar peptide maps of their respective envelope gp120s, as determined by two-dimensional chymotrypsin oligopeptide analysis. One peptide, however, from the original HTLV-IIIB-inoculated virus was deleted in viruses from all three animals, and in addition, we noted the appearance of a new or modified peptide which

  20. Persistent infection of chimpanzees with human immunodeficiency virus: serological responses and properties of reisolated viruses.

    PubMed

    Nara, P L; Robey, W G; Arthur, L O; Asher, D M; Wolff, A V; Gibbs, C J; Gajdusek, D C; Fischinger, P J

    1987-10-01

    Persistent infection by human immunodeficiency virus (HIV-1) in the chimpanzee may be valuable for immunopathologic and potential vaccine evaluation. Two HIV strains, the tissue culture-derived human T-cell lymphotropic virus type IIIB (HTLV-IIIB) and in vivo serially passaged lymphadenopathy-associated virus type 1 (LAV-1), were injected intravenously into chimpanzees. Two animals received HTLV-IIIB as either virus-infected H9 cells or cell-free virus. A third animal received chimpanzee-passaged LAV-1. Evaluation of their sera for virus-specific serologic changes, including neutralizations, was done during a 2-year period. During this period all animals had persistently high titers of antibodies to viral core and envelope antigens. All three animals developed a progressively increasing type-specific neutralizing LAV-1 versus HTLV-IIIB antibody titer during the 2-year observation period which broadened in specificity to include HTLV-HIRF, HTLV-IIIMN, and HTLV-IIICC after 6 to 12 months. The antibody titers against both viruses were still increasing by 2 years after experimental virus inoculation. Sera from all animals were capable of neutralizing both homologously and heterologously reisolated virus from chimpanzees. A slightly more rapid type-specific neutralizing response was noted for the animal receiving HTLV-IIIB-infected cells compared with that for cell-free HTLV-IIIB. Sera from all persistently infected chimpanzees were capable of mediating group-specific antibody-mediated complement-dependent cytolysis of HIV-infected cells derived from all isolates tested. Viruses reisolated from all three animals at 20 months after inoculation revealed very similar peptide maps of their respective envelope gp120s, as determined by two-dimensional chymotrypsin oligopeptide analysis. One peptide, however, from the original HTLV-IIIB-inoculated virus was deleted in viruses from all three animals, and in addition, we noted the appearance of a new or modified peptide which

  1. 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

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

    PubMed Central

    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

  3. Human Immunodeficiency Virus Type 1 Monoclonal Antibodies Suppress Acute Simian-Human Immunodeficiency Virus Viremia and Limit Seeding of Cell-Associated Viral Reservoirs

    PubMed Central

    Pegu, Amarendra; Wang, Keyun; McGinnis, Kathleen; Nason, Martha; Foulds, Kathryn; Letukas, Valerie; Schmidt, Stephen D.; Chen, Xuejun; Todd, John Paul; Lifson, Jeffrey D.; Rao, Srinivas; Michael, Nelson L.; Robb, Merlin L.; Mascola, John R.; Koup, Richard A.

    2015-01-01

    ABSTRACT Combination antiretroviral therapy (cART) administered shortly after human immunodeficiency virus type 1 (HIV-1) infection can suppress viremia and limit seeding of the viral reservoir, but lifelong treatment is required for the majority of patients. Highly potent broadly neutralizing HIV-1 monoclonal antibodies (MAbs) can reduce plasma viremia when administered during chronic HIV-1 infection, but the therapeutic potential of these antibodies during acute infection is unknown. We tested the ability of HIV-1 envelope glycoprotein-specific broadly neutralizing MAbs to suppress acute simian-human immunodeficiency virus (SHIV) replication in rhesus macaques. Four groups of macaques were infected with SHIV-SF162P3 and received (i) the CD4-binding-site MAb VRC01; (ii) a combination of a more potent clonal relative of VRC01 (VRC07-523) and a V3 glycan-dependent MAb (PGT121); (iii) daily cART, all on day 10, just prior to expected peak plasma viremia; or (iv) no treatment. Daily cART was initiated 11 days after MAb administration and was continued for 13 weeks in all treated animals. Over a period of 11 days after a single administration, MAb treatment significantly reduced peak viremia, accelerated the decay slope, and reduced total viral replication compared to untreated controls. Proviral DNA in lymph node CD4 T cells was also diminished after treatment with the dual MAb. These data demonstrate the virological effect of potent MAbs and support future clinical trials that investigate HIV-1-neutralizing MAbs as adjunctive therapy with cART during acute HIV-1 infection. IMPORTANCE Treatment of chronic HIV-1 infection with potent broadly neutralizing HIV-1 MAbs has been shown to significantly reduce plasma viremia. However, the antiviral effect of MAb treatment during acute HIV-1 infection is unknown. Here, we demonstrate that MAbs targeting the HIV-1 envelope glycoprotein both suppress acute SHIV plasma viremia and limit CD4 T cell-associated viral DNA. These

  4. 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

  5. Characterization of human immunodeficiency viruses resistant to oxathiolane-cytosine nucleosides.

    PubMed Central

    Schinazi, R F; Lloyd, R M; Nguyen, M H; Cannon, D L; McMillan, A; Ilksoy, N; Chu, C K; Liotta, D C; Bazmi, H Z; Mellors, J W

    1993-01-01

    The (-) enantiomers of 2',3'-dideoxy-5-fluoro-3'-thiacytidine [(-)-FTC] and 2',3'-dideoxy-3'-thiacytidine [(-)-BCH-189] were recently shown to inhibit selectively human immunodeficiency viruses (HIV) and hepatitis B virus in vitro. In the current study, the potential for HIV type 1 (HIV-1) resistance to these compounds was evaluated by serial passage of the virus in human peripheral blood mononuclear cells and MT-2 cells in the presence of increasing drug concentrations. Highly drug-resistant HIV-1 variants dominated the replicating virus population after two or more cycles of infection. The resistant variants were cross-resistant to (-)-FTC, (-)-BCH-189, and their (+) congeners but remained susceptible to 2',3'-dideoxycytidine, 3'-azido-3'-deoxythymidine, 3'-fluoro-3'-deoxythymidine, 2',3'-dideoxyinosine, phosphonoformate, the TIBO compound R82150, and the bis(heteroaryl)piperazine derivative U-87201E. Reverse transcriptase derived from drug-resistant viral particles was 15- to 50-fold less susceptible to the 5'-triphosphates of FTC and BCH-189 compared with enzyme from parental drug-susceptible virus. DNA sequence analysis of the reverse transcriptase gene amplified from resistant viruses consistently identified mutations at codon 184 from Met (ATG) to Val (GTG or GTA) or Ile (ATA). Sequence analysis of amplified reverse transcriptase from a patient who had received (-)-BCH-189 therapy for 4 months demonstrated a mixture of the Met-184-to-Val (GTG) mutation and the parental genotype, indicating that the Met-184 mutation can occur in vivo. Images PMID:7684216

  6. 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

  7. 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

  8. Global Impact of Human Immunodeficiency Virus and AIDS

    PubMed Central

    Gayle, Helene D.; Hill, Gena L.

    2001-01-01

    This review provides information on the epidemiology, economic impact, and intervention strategies for the human immunodeficiency virus (HIV)/AIDS pandemic in developing countries. According to the World Health Organization and the Joint United Nations Programme on HIV/AIDS (UNAIDS) at the end of 1999, an estimated 34.3 million people were living with HIV/AIDS. Most of the people living with HIV, 95% of the global total, live in developing countries. Examples of the impact of HIV/AIDS in Africa, Asia, Latin America, the Caribbean, and the Newly Independent States provide insight into the demographics, modes of exposure, treatment and prevention options, and the economic effect of the epidemic on the global community. The epidemic in each region of the world is influenced by the specific risk factors that are associated with the spread of HIV/AIDS and the responses that have evolved to address it. These influences are important in developing HIV/AIDS policies and programs to effectively address the global pandemic. PMID:11292641

  9. 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.

  10. 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.

  11. 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

  12. Screening for Cognitive Impairment in Human Immunodeficiency Virus

    PubMed Central

    Paul, Robert; Chiao, Stephanie; Wendelken, Lauren A.; Miller, Bruce

    2011-01-01

    Recent publications estimate the prevalence of human immunodeficiency virus (HIV)–associated neurocognitive disorders (HAND) exceeds 50%, and this rate is likely higher among older patients. Cognitive impairment may impact medication adherence, and symptomatic impairment has been linked to all-cause mortality providing some impetus for early detection. There are currently insufficient data to inform solid recommendations on screening methods. Most HIV-specific tools have poor performance characteristics for all but the most severe form of impairment, which accounts for <5% of cases. Reliance on symptoms is likely to miss a substantial proportion of individuals with HAND due to poor insight, confounding mood disturbances, and lack of well-informed proxies. In the aging HIV-positive population, broader screening tools may be required to allow sensitivity for both HIV and neurodegenerative disorders. We describe the clinical presentation of HAND, review existing data related to screening tools, and provide preliminary and practical recommendations in the absence of more definitive studies. PMID:21921226

  13. 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

  14. Human Immunodeficiency Virus Infection and Host Defense in the Lungs.

    PubMed

    Charles, Tysheena P; Shellito, Judd E

    2016-04-01

    Immunosuppression associated with human immunodeficiency virus (HIV) infection impacts all components of host defense against pulmonary infection. Cells within the lung have altered immune function and are important reservoirs for HIV infection. The host immune response to infected lung cells further compromises responses to a secondary pathogenic insult. In the upper respiratory tract, mucociliary function is impaired and there are decreased levels of salivary immunoglobulin A. Host defenses in the lower respiratory tract are controlled by alveolar macrophages, lymphocytes, and polymorphonuclear leukocytes. As HIV infection progresses, lung CD4 T cells are reduced in number causing a lack of activation signals from CD4 T cells and impaired defense by macrophages. CD8 T cells, on the other hand, are increased in number and cause lymphocytic alveolitis. Specific antibody responses by B-lymphocytes are decreased and opsonization of microorganisms is impaired. These observed defects in host defense of the respiratory tract explain the susceptibility of HIV-infected persons for oropharyngeal candidiasis, bacterial pneumonia, Pneumocystis pneumonia, and other opportunistic infections. PMID:26974294

  15. Noninfectious Pulmonary Complications of Human Immunodeficiency Virus Infection

    PubMed Central

    Staitieh, Bashar

    2014-01-01

    Abstract: Human immunodeficiency virus type 1 (HIV-1) is the retrovirus responsible for the development of AIDS. Its profound impact on the immune system leaves the host vulnerable to a wide range of opportunistic infections not seen in individuals with a competent immune system. Pulmonary infections dominated the presentations in the early years of the epidemic, and infectious and noninfectious lung diseases remain the leading causes of morbidity and mortality in persons living with HIV despite the development of effective antiretroviral therapy. In addition to the long known immunosuppression and infection risks, it is becoming increasingly recognized that HIV promotes the risk of noninfectious pulmonary diseases through a number of different mechanisms, including direct tissue toxicity by HIV-related viral proteins and the secondary effects of coinfections. Diseases of the airways, lung parenchyma and the pulmonary vasculature, as well as pulmonary malignancies, are either more frequent in persons living with HIV or have atypical presentations. As the pulmonary infectious complications of HIV are generally well known and have been reviewed extensively, this review will focus on the breadth of noninfectious pulmonary diseases that occur in HIV-infected individuals as these may be more difficult to recognize by general medical physicians and subspecialists caring for this large and uniquely vulnerable population. PMID:24992395

  16. Novel inhibitors of human immunodeficiency virus type 2 infectivity.

    PubMed

    Beach, Lauren B; Rawson, Jonathan M; Kim, Baek; Patterson, Steven E; Mansky, Louis M

    2014-12-01

    Human immunodeficiency virus type 2 (HIV-2) infects about two million people worldwide. HIV-2 has fewer treatment options than HIV-1, yet may evolve drug resistance more quickly. We have analysed several novel drugs for anti-HIV-2 activity. It was observed that 5-azacytidine, clofarabine, gemcitabine and resveratrol have potent anti-HIV-2 activity. The EC50 values for 5-azacytidine, clofarabine and resveratrol were found to be significantly lower with HIV-2 than with HIV-1. A time-of-addition assay was used to analyse the ability of these drugs to interfere with HIV-2 replication. Reverse transcription was the likely target for antiretroviral activity. Taken together, several novel drugs have been discovered to have activity against HIV-2. Based upon their known activities, these drugs may elicit enhanced HIV-2 mutagenesis and therefore be useful for inducing HIV-2 lethal mutagenesis. In addition, the data are consistent with HIV-2 reverse transcriptase being more sensitive than HIV-1 reverse transcriptase to dNTP pool alterations. PMID:25103850

  17. 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

  18. 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.

  19. 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

  20. Enhanced expression of human immunodeficiency virus type 1 correlates with development of AIDS.

    PubMed

    Gupta, P; Kingsley, L; Armstrong, J; Ding, M; Cottrill, M; Rinaldo, C

    1993-10-01

    The progression to AIDS may be significantly related to the level of human immunodeficiency virus type 1 (HIV-1) replication. We have used quantitative cell culture and quantitative DNA and RNA PCR to measure viral load and expression in peripheral blood mononuclear cells obtained cross-sectionally and longitudinally from HIV-1-seropositive homosexual men enrolled in the Multicenter AIDS Cohort Study. Our results indicate that the number of circulating CD4+ T-lymphocytes producing HIV-1 increased as the total number of CD4+ T-cells declined. However, there was no correlation between the number of HIV-1-producing CD4+ cells and the duration of infection. Furthermore, the level of HIV-1 gag RNA increased as the disease progressed and CD4+ cell numbers declined. Subjects who remained asymptomatic with stable CD4+ cell counts, however, maintained a very low level of HIV-1 RNA expression during the entire period of follow-up (38-71 months). In contrast to viral RNA expression, the level of proviral DNA did not change significantly as the disease progressed. However, the level of proviral DNA was significantly higher in AIDS patients than in men who remained asymptomatic. Such increased levels of HIV-1 DNA were detected 34-68 months before the development of AIDS. These results support the role of HIV-1 RNA expression in the development of AIDS. PMID:8103948

  1. 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

  2. Opposite Effects of SDF-1 on Human Immunodeficiency Virus Type 1 Replication

    PubMed Central

    Maréchal, Valérie; Arenzana-Seisdedos, Fernando; Heard, Jean-Michel; Schwartz, Olivier

    1999-01-01

    The α-chemokine SDF-1 binds CXCR4, a coreceptor for human immunodeficiency virus type 1 (HIV-1), and inhibits viral entry mediated by this receptor. Since chemokines are potent chemoattractants and activators of leukocytes, we examined whether the stimulation of HIV target cells by SDF-1 affects the replication of virus with different tropisms. We observed that SDF-1 inhibited the entry of X4 strains and increased the infectivity of particles bearing either a CCR5-tropic HIV-1 envelope or a vesicular stomatitis virus G envelope. In contrast to the inhibitory effect of SDF-1 on X4 strains, which is at the level of entry, the stimulatory effect does not involve envelope-receptor interactions or proviral DNA synthesis. Rather, we observed an increased ability of Tat to transactivate the HIV-1 long terminal repeat in the presence of the chemokine. Therefore, the effects of SDF-1 on the HIV-1 life cycle can be multiple and opposite, including both an inhibition of viral entry and a stimulation of proviral gene expression. PMID:10196252

  3. Combinations of 3'-azido-3'-deoxythymidine (zidovudine) and phosphonoformate (foscarnet) against human immunodeficiency virus type 1 and cytomegalovirus replication in vitro.

    PubMed Central

    Eriksson, B F; Schinazi, R F

    1989-01-01

    Combinations of 3'-azido-3'-deoxythymidine and phosphonoformate produced a moderate synergistic inhibitory effect against human immunodeficiency virus type 1 in vitro at concentrations that are easily achieved in humans. The synergistic effect was more pronounced with increasing concentrations and was not secondary to toxic effects of the drugs. 3'-Azido-3'-deoxythymidine neither inhibited the replication of human cytomegalovirus in human embryonic lung fibroblasts nor interfered with the anticytomegalovirus effect of phosphonoformate. By using partially purified reverse transcriptase of human immunodeficiency virus type 1 and human cytomegalovirus DNA polymerase, various combinations of 3'-azido-3'-deoxythymidine-5'-triphosphate and phosphonoformate produced strong indications of additive interactions. The synergistic interactions in infected cells and the additive effects observed at the reverse transcriptase level indicate that mechanisms other than the reverse transcriptase may be of importance for the inhibition of human immunodeficiency virus replication by these two compounds. A concomitant treatment of cytomegalovirus infections, such as cytomegalovirus retinitis, with phosphonoformate in patients with acquired immunodeficiency syndrome receiving 3'-azido-3'-deoxythymidine may be appropriate, and this combination may also be useful in controlling human immunodeficiency virus infection. PMID:2546487

  4. 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

  5. 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.

  6. Conditional Immune Escape during Chronic Simian Immunodeficiency Virus Infection

    PubMed Central

    Gellerup, Dane D.; Balgeman, Alexis J.; Nelson, Chase W.; Ericsen, Adam J.; Scarlotta, Matthew; Hughes, Austin L.

    2015-01-01

    ABSTRACT Anti-HIV CD8 T cells included in therapeutic treatments will need to target epitopes that do not accumulate escape mutations. Identifying the epitopes that do not accumulate variants but retain immunogenicity depends on both host major histocompatibility complex (MHC) genetics and the likelihood for an epitope to tolerate variation. We previously found that immune escape during acute SIV infection is conditional; the accumulation of mutations in T cell epitopes is limited, and the rate of accumulation depends on the number of epitopes being targeted. We have now tested the hypothesis that conditional immune escape extends into chronic SIV infection and that epitopes with a preserved wild-type sequence have the potential to elicit epitope-specific CD8 T cells. We deep sequenced simian immunodeficiency virus (SIV) from Mauritian cynomolgus macaques (MCMs) that were homozygous and heterozygous for the M3 MHC haplotype and had been infected with SIV for about 1 year. When interrogating variation within individual epitopes restricted by M3 MHC alleles, we found three categories of epitopes, which we called categories A, B, and C. Category B epitopes readily accumulated variants in M3-homozygous MCMs, but this was less common in M3-heterozygous MCMs. We then determined that chronic CD8 T cells specific for these epitopes were more likely preserved in the M3-heterozygous MCMs than M3-homozygous MCMs. We provide evidence that epitopes known to escape from chronic CD8 T cell responses in animals that are homozygous for a set of MHC alleles are preserved and retain immunogenicity in a host that is heterozygous for the same MHC alleles. IMPORTANCE Anti-HIV CD8 T cells that are part of therapeutic treatments will need to target epitopes that do not accumulate escape mutations. Defining these epitope sequences is a necessary precursor to designing approaches that enhance the functionality of CD8 T cells with the potential to control virus replication during chronic

  7. Direct comparison of antigen production and induction of apoptosis by canarypox virus- and modified vaccinia virus ankara-human immunodeficiency virus vaccine vectors.

    PubMed

    Zhang, Xiugen; Cassis-Ghavami, Farah; Eller, Mike; Currier, Jeff; Slike, Bonnie M; Chen, Xuemin; Tartaglia, James; Marovich, Mary; Spearman, Paul

    2007-07-01

    Recombinant poxvirus vectors are undergoing intensive evaluation as vaccine candidates for a variety of infectious pathogens. Avipoxviruses, such as canarypox virus, are replication deficient in mammalian cells by virtue of a poorly understood species-specific restriction. Highly attenuated vaccinia virus strains such as modified vaccinia virus Ankara (MVA) are similarly unable to complete replication in most mammalian cells but have an abortive-late phenotype, in that the block to replication occurs post-virus-specific DNA replication. In this study, an identical expression cassette for human immunodeficiency virus gag, pro, and env coding sequences was placed in canarypox virus and MVA vector backbones in order to directly compare vector-borne expression and to analyze differences in vector-host cell interactions. Antigen production by recombinant MVA was shown to be greater than that from recombinant canarypox virus in the mammalian cell lines and in the primary human cells tested. This observation was primarily due to a longer duration of antigen production in recombinant MVA-infected cells. Apoptosis induction was found to be more profound with the empty canarypox virus vector than with MVA. Remarkably, however, the inclusion of a gag/pro/env expression cassette altered the kinetics of apoptosis induction in recombinant MVA-infected cells to levels equal to those found in canarypox virus-infected cells. Antigen production by MVA was noted to be greater in human dendritic cells and resulted in enhanced T-cell stimulation in an in vitro antigen presentation assay. These results reveal differences in poxvirus vector-host cell interactions that should be relevant to their use as immunization vehicles. PMID:17409140

  8. Direct Comparison of Antigen Production and Induction of Apoptosis by Canarypox Virus- and Modified Vaccinia Virus Ankara-Human Immunodeficiency Virus Vaccine Vectors▿

    PubMed Central

    Zhang, Xiugen; Cassis-Ghavami, Farah; Eller, Mike; Currier, Jeff; Slike, Bonnie M.; Chen, Xuemin; Tartaglia, James; Marovich, Mary; Spearman, Paul

    2007-01-01

    Recombinant poxvirus vectors are undergoing intensive evaluation as vaccine candidates for a variety of infectious pathogens. Avipoxviruses, such as canarypox virus, are replication deficient in mammalian cells by virtue of a poorly understood species-specific restriction. Highly attenuated vaccinia virus strains such as modified vaccinia virus Ankara (MVA) are similarly unable to complete replication in most mammalian cells but have an abortive-late phenotype, in that the block to replication occurs post-virus-specific DNA replication. In this study, an identical expression cassette for human immunodeficiency virus gag, pro, and env coding sequences was placed in canarypox virus and MVA vector backbones in order to directly compare vector-borne expression and to analyze differences in vector-host cell interactions. Antigen production by recombinant MVA was shown to be greater than that from recombinant canarypox virus in the mammalian cell lines and in the primary human cells tested. This observation was primarily due to a longer duration of antigen production in recombinant MVA-infected cells. Apoptosis induction was found to be more profound with the empty canarypox virus vector than with MVA. Remarkably, however, the inclusion of a gag/pro/env expression cassette altered the kinetics of apoptosis induction in recombinant MVA-infected cells to levels equal to those found in canarypox virus-infected cells. Antigen production by MVA was noted to be greater in human dendritic cells and resulted in enhanced T-cell stimulation in an in vitro antigen presentation assay. These results reveal differences in poxvirus vector-host cell interactions that should be relevant to their use as immunization vehicles. PMID:17409140

  9. Cutaneous Co-infected Cytomegalovirus and Herpes Simplex Virus Perigenital Ulcers in Human Immunodeficiency Virus Patients.

    PubMed

    Schoenfeld, Jason; Cannon, Sarah; Cam, Kristin; Keller, Matthew

    2013-10-01

    There is uncertainty regarding the pathogenic nature of cytomegalovirus in cutaneous lesions co-infected with herpes simplex virus. It is widely believed that herpes simplex virus is the main pathogenic factor in such lesions and that cytomegalovirus plays little if any role. There are, however, isolated case reports that describe cytomegalovirus as an important driving pathogen in such lesions. The authors present two human immunodeficiency virus patients who have cytomegalovirus and herpes simplex virus co-infected perigenital ulcers, one of whom improved on valacyclovir, while the other, who was already on valacyclovir for chronic herpes simplex virus suppression, showed no improvement with a single dose of cidofovir. He only showed rapid improvement when treated with valganciclovir. The latter patient underscores the viewpoint that at least in some cases, cytomegalovirus may be an important driving force behind the formation of such lesions. The authors therefore recommend that clinicians be aware of the possible pathogenic role of cytomegalovirus in these ulcers, and, in nonhealing ulcers, use anti-cytomegalovirus agents to prevent the onset of systemic disease. These results warrant further study of the pathogenesis of cytomegalovirus in co-infected herpes simplex virus ulcers. PMID:24155993

  10. Mutations in Human Immunodeficiency Virus Type 1 Nucleocapsid Protein Zinc Fingers Cause Premature Reverse Transcription ▿

    PubMed Central

    Thomas, James A.; Bosche, William J.; Shatzer, Teresa L.; Johnson, Donald G.; Gorelick, Robert J.

    2008-01-01

    Human immunodeficiency virus type 1 (HIV-1) requires that its genome be reverse transcribed into double-stranded DNA for productive infection of cells. This process requires not only reverse transcriptase but also the nucleocapsid protein (NC), which functions as a nucleic acid chaperone. Reverse transcription generally begins once the core of the virion enters the cytoplasm of a newly infected cell. However, some groups have reported the presence of low levels of viral DNA (vDNA) within particles prior to infection, the significance and function of which is controversial. We report here that several HIV-1 NC mutants, which we previously identified as being replication defective, contain abnormally high levels of intravirion DNA. These findings were further reinforced by the inability of these NC mutants to perform endogenous reverse transcription (ERT), in contrast to the readily measurable ERT activity in wild-type HIV-1. When either of the NC mutations is combined with a mutation that inactivates the viral protease, we observed a significant reduction in the amount of intravirion DNA. Interestingly, we also observed high levels of intravirion DNA in the context of wild-type NC when we delayed budding by means of a PTAP(−) (Pro-Thr-Ala-Pro) mutation. Premature reverse transcription is most probably occurring before these mutant virions bud from producer cells, but we fail to see any evidence that the NC mutations alter the timing of Pr55Gag processing. Critically, our results also suggest that the presence of intravirion vDNA could serve as a diagnostic for identifying replication-defective HIV-1. PMID:18667500

  11. CCR6 Functions as a New Coreceptor for Limited Primary Human and Simian Immunodeficiency Viruses

    PubMed Central

    Islam, Salequl; Shimizu, Nobuaki; Hoque, Sheikh Ariful; Jinno-Oue, Atsushi; Tanaka, Atsushi; Hoshino, Hiroo

    2013-01-01

    More than 12 chemokine receptors (CKRs) have been identified as coreceptors for the entry of human immunodeficiency virus type 1 (HIV-1), type 2 (HIV-2), and simian immunodeficiency viruses (SIVs) into target cells. The expression of CC chemokine receptor 6 (CCR6) on Th17 cells and regulatory T cells make the host cells vulnerable to HIV/SIV infection preferentially. However, only limited information is available concerning the specific role of CCR6 in HIV/SIV infection. We examined CCR6 as a coreceptor candidate in this study using NP-2 cell line-based in-vitro studies. Normally, CD4-transduced cell line, NP-2/CD4, is strictly resistant to all HIV/SIV infection. When CCR6 was transduced there, the resultant NP-2/CD4/CCR6 cells became susceptible to HIV-1HAN2, HIV-2MIR and SIVsmE660, indicating coreceptor roles of CCR6. Viral antigens in infected cells were detected by IFA and confirmed by detection of proviral DNA. Infection-induced syncytia in NP-2/CD4/CCR6 cells were detected by Giemsa staining. Amount of virus release through CCR6 has been detected by RT assay in spent culture medium. Sequence analysis of proviral DNA showed two common amino acid substitutions in the C2 envelope region of HIV-2MIR clones propagated through NP-2/CD4/CCR6 cells. Conversely, CCR6-origin SIVsmE660 clones resulted two amino acid changes in the V1 region and one change in the C2 region. The substitutions in the C2 region for HIV-2MIR and the V1 region of SIVsmE660 may confer selection advantage for CCR6-use. Together, the results describe CCR6 as an independent coreceptor for HIV and SIV in strain-specific manner. The alteration of CCR6 uses by viruses may influence the susceptibility of CD4+ CCR6+ T-cells and dendritic cell subsets in vivo and therefore, is important for viral pathogenesis in establishing latent infections, trafficking, and transmission. However, clinical relevance of CCR6 as coreceptor in HIV/SIV infections should be investigated further. PMID:24009735

  12. Importance of the intracytoplasmic domain of the simian immunodeficiency virus (SIV) envelope glycoprotein for pathogenesis.

    PubMed

    Luciw, P A; Shaw, K E; Shacklett, B L; Marthas, M L

    1998-12-01

    SIVmac1A11 and SIVmac239 are nonpathogenic and pathogenic molecular clones in rhesus macaques, respectively. Although these viruses exhibit approximately 98% nucleotide and amino acid sequence homology, differences are found in the length of the translation frames for several genes. SIVmac239 has a premature stop codon in nef, whereas SIVmac1A11 has a premature stop codon in vpr and two premature stop codons in the intracytoplasmic domain of the env-transmembrane (TM) subunit. Recombinant viruses, constructed through reciprocal exchange of large DNA restriction enzyme fragments between SIVmac1A11 and SIVmac239, were evaluated in adult rhesus macaques. This in vivo analysis revealed that two or more regions of the SIVmac genome were essential for high virus load and disease progression (Marthas et al., 1993. J. Virol. 67, 6047-6055). An important gap in knowledge remaining from this study was whether the premature stop codons in env-TM of recombinant virus SIV1A11/239gag-env/1A11 (Full-length vpr and nef, two stop codons in env-TM) reverted to coding triplets in vivo. Here, we report that viral sequences in macaques, which succumbed to an AIDS-like disease after infection with SIV1A11/239gag-env/1A11, exhibited reversion of both env-TM stop codons. In addition, antibodies to the intracytoplasmic domain of env-TM were detected in macaques containing revertant virus and showing disease; this finding indicates that this domain of the env glycoprotein was expressed in vivo. Thus selection for viral variants with full-length env-TM demonstrated that the cytoplasmic domain of the SIVmac env glycoprotein plays a role in viral persistence and immunodeficiency in primates. PMID:9875311

  13. Human Immunodeficiency Virus Type 1 Subtypes Prevalence in Central China

    PubMed Central

    Wang, Zhe; Li, Wen-jie

    2009-01-01

    Purpose To study the epidemic characteristics, transmission sources and routes of various subtypes of human immunodeficiency virus type 1 (HIV-1) and sequence variations in Henan, central China. To provide theoretical foundation for Acquired Immune Deficiency Syndrome (AIDS) prevention strategy in this region where the primary HIV transmission route was through former paid blood donation. Materials and Methods HIV-1 gene env and gag were amplified by nested polymerase chain reaction (PCR) from uncultured peripheral blood mononuclear cells (PBMCs) obtained from 1,287 HIV-1 confirmed samples in Henan. Results Among 1,287 samples, 5 HIV-1 strains were found including subtypes B' (95.9%), C (0.47%) and recombinant subtypes CRF 07_BC (1.09%), CRF 08_BC (1.79%) and CRF 01_AE (0.78%). Phylogenetic tree analysis found that 1,234 Henan subtype B' were closely related to those commonly found in Thailand, and were distantly related to other international subtypes. The dominant strain in former blood plasma donors (FPDs) was subtype B', and the dominant strains in sexual transmission were subtype B' and BC. Among HIV patients who were most likely infected through routes other than paid blood donation, the percentage of non-B' subtypes was much higher than those of FPD. Conclusion These findings suggest that the prevailing strain of HIV-1 in Henan is subtype B', similar to the B' subtype found in Thailand. In addition, for the first time we found subtypes C and recombinant subtypes CRF07_BC, CRF08_BC and CRF01_AE in this region. Indicating that the subtype feature of HIV-1 became more complicated than before in central China. PMID:19881967

  14. 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

  15. 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

  16. 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

  17. 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

  18. Human immunodeficiency virus (HIV)-related pulmonary complications in pregnancy.

    PubMed

    Saade, G R

    1997-08-01

    With changes in the demographics of human immunodeficiency virus (HIV) infection, women and children are becoming the fastest growing group of newly infected patients. With longer survival after HIV infection, more women infected with HIV are becoming pregnant. Pulmonary disease is one of the most common presenting conditions in an AIDS-defining illness. Pneumocystis carini pneumonia and tuberculosis are the most common disorders that herald the onset of AIDS. They are also the most frequently encountered HIV-related pulmonary complications during pregnancy. Others have been rarely reported during pregnancy and include fungal infections (Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitus), bacterial infections (Haemophilus influenzae and Streptococcus pneumoniae along with Pseudomona aeruginosa), viral infections (CMV), opportunistic neoplasms (Kaposi's sarcoma, lymphoma) and miscellaneous conditions peculiar to HIV-infected individuals (nonspecific interstitial pneumonitis, lymphoid interstitial pneumonitis, isolated pulmonary hypertension, and pulmonary edema secondary to cardiac disease or drug abuse). Most of the data regarding the pulmonary complications of HIV infection come from studies in nonpregnant patients. The extent to which pregnancy affects the course of respiratory disease in HIV infection and vice versa is not well documented. Clinical presentation is usually not altered by pregnancy. Except for minor modifications mainly related to potential fetal effects, the diagnostic work-up and management are similar to those in the nonpregnant patient. The most important effect of pregnancy on these conditions remains the delay in diagnosis and treatment. A high index of suspicion should, therefore, be maintained. In addition, most prophylactic measures recommended in nonpregnant HIV-infected individuals also apply to pregnant women. PMID:9298723

  19. Antiretroviral treatment of human immunodeficiency virus infection: Swedish recommendations.

    PubMed

    Sandström, Eric; Uhnoo, Ingrid; Ahlqvist-Rastad, Jane; Bratt, Göran; Berglund, Torsten; Gisslén, Magnus; Lindbäck, Stefan; Morfeldt, Linda; Ståhle, Lars; Sönnerborg, Anders

    2003-01-01

    The Swedish guidelines (SwG) for treatment of human immunodeficiency virus (HIV) infection have several important roles. A major task involves the promotion of a uniformly high standard of care in all HIV treatment clinics in Sweden and the identification of strengths, weaknesses and relevance of recent research findings. CD4+ T-cell counts < 200 cells/microl are clear indications for the initiation of treatment, whereas high viral loads serve as an indication for increased vigilance rather than a criterion for therapy. It is recommended that the first regimen consists of 2 nucleoside reverse transcriptase inhibitors in combination with 1 protease inhibitor or 1 non-nucleoside reverse transcriptase inhibitor. The definition of treatment failure is rigorous. Treatment change should be considered if the viral load has not fallen by at least 1.5 log in 4 weeks or is undetectable within 3-4 months. Resistance testing is endorsed at primary infection, in the event of treatment failure and in pregnant women. Interaction with experts in HIV resistance testing is emphasized. Therapeutic drug monitoring is advocated. Patients with treatment failure should be handled individually and the decision on therapeutic strategy should be based on treatment history, resistance testing and other clinical facts. The SwG do not give recommendations for some important issues such as prolonged drug holidays and preferences in initial treatment regimens. More scientific data are likely to be available soon and the SwG will be refined accordingly. The present guidelines are translated from Swedish; they are published on the Medical Products Agency (MPA) and Swedish Reference Group for Antiviral Therapy (RAV) websites (www.mpa.se and www.rav.nu.se), including 7 separate papers based on a thorough literature search. A complete reference list is available on request from the MPA. PMID:12751710

  20. Ocular findings in human immunodeficiency virus patients in Washington, DC.

    PubMed

    Kaleem, Mona A; Ramsahai, Shweta; Del Fierro, Katrina; Rasul, Samad; Onumah, Chavon; Lerebours, Valerie; Gajjala, Jhansi; Copeland, Robert A; Jones, Leslie S

    2012-04-01

    The purpose of the study was to determine the prevalence of ocular diseases in human immunodeficiency virus (HIV) patients in Washington, DC in the era of highly active antiretroviral therapy (HAART). This was a cross-sectional study of patients with HIV who were seen by the ophthalmology consultation service between September 2003 and May 2011 at a single academic institution in Washington, DC. Medical history and ophthalmic findings were reviewed. Patients with complete laboratory data dated within 3 months of their presenting eye examination were included. Descriptive statistics were performed. The records of 151 patients were included in the final analysis. All patients had complete laboratory data dated within 3 months of their presenting eye examination. Sixty-eight (45 %) patients and fifty-eight (50 %) of those with a diagnosis of acquired immune deficiency syndrome (AIDS) were diagnosed with an HIV-related ophthalmic disease. The leading anterior segment disease was herpes zoster ophthalmicus and the leading posterior segment disease was HIV retinopathy. Of the 151 included patients, 78 (52 %) were receiving HAART at the time of the examination. Thirty-one (42 %) of those not receiving HAART were diagnosed with an HIV-related ophthalmic disease. In this study, we find that the overall prevalence of ocular disease has decreased since the introduction of HAART. However, HIV patients continue to be predisposed to developing ophthalmic disease at higher rates than the general population. Visual dysfunction remains an important source of morbidity in HIV patients, particularly in those with AIDS. Measures for improvement include increased communication between infectious disease specialists and ophthalmologists to ensure adherence to HAART and routine eye examinations. PMID:22450559

  1. Perioperative concerns in neurosurgical patients with human immunodeficiency virus infection

    PubMed Central

    Agarwal, Jyotsna; Ganjoo, Pragati; Hansda, Upendra; Sharma, Megha U.; Tandon, Monica S.; Singh, Daljit

    2016-01-01

    Background: The perioperative management of human immunodeficiency virus (HIV) infected patients undergoing neurosurgery is challenging due to the presence of HIV-related multi-system derangements, opportunistic infections and malignancies, history of substance abuse, and adverse effects of anti-retroviral therapy (ART), together with the inherent risks of neurosurgery. The possible adverse impact of HIV disease on the anesthetic outcome due to the associated co-morbidities, and conversely, the role of surgery and anesthesia in HIV disease progression due to their immunosuppressive effects, and also, the fear of HIV transmission among the attending medical personnel are the important perioperative concerns in such surgeries. Aim: To present our experience in the perioperative management of HIV-infected patients who underwent neurosurgery at our institute in the past 5 years and highlight the relevant perioperative issues. Materials and Methods: A retrospective analysis of the records of HIV-infected neurosurgical patients was undertaken to determine their HIV status and ART, anesthesia and surgery details, perioperative complications, and instances of postoperative worsening of HIV disease or its transmission, if any. Results: Seven HIV infected patients with variable severity of HIV infection and systemic disease underwent neurosurgery for different indications. Their perioperative management was modified in accordance with the co-morbidities and the type of neurosurgery. There was no obvious adverse impact of the HIV disease on the anesthetic outcome, no obvious clinical evidence of post-surgery worsening of the HIV disease, and no instance of HIV transmission in our patients. Conclusion: A goodunderstanding of the HIV disease and its perioperative implications during neurosurgery helps in better patient management and enables a safe outcome. PMID:27057214

  2. 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.

  3. Utilization of C-C chemokine receptor 5 by the envelope glycoproteins of a pathogenic simian immunodeficiency virus, SIVmac239.

    PubMed Central

    Marcon, L; Choe, H; Martin, K A; Farzan, M; Ponath, P D; Wu, L; Newman, W; Gerard, N; Gerard, C; Sodroski, J

    1997-01-01

    We examined chemokine receptors for the ability to facilitate the infection of CD4-expressing cells by viruses containing the envelope glycoproteins of a pathogenic simian immunodeficiency virus, SIVmac239. Expression of either human or simian C-C chemokine receptor CCR5 allowed the SIVmac239 envelope glycoproteins to mediate virus entry and cell-to-cell fusion. Thus, distantly related immunodeficiency viruses such as SIV and the primary human immunodeficiency virus type 1 isolates can utilize CCR5 as an entry cofactor. PMID:9032394

  4. A novel human immunodeficiency virus type 1 protein, tev, shares sequences with tat, env, and rev proteins.

    PubMed Central

    Benko, D M; Schwartz, S; Pavlakis, G N; Felber, B K

    1990-01-01

    We have characterized a novel 28-kilodalton protein, p28tev, detected in human immunodeficiency virus type 1-infected cells. tev is recognized by both tat and rev monospecific antibodies. tev is initiated at the tat AUG and contains the first exon of tat at its amino terminus, a small portion of env in the middle, and the second exon of rev at its carboxy terminus. A cDNA clone producing tev was cloned and expressed in human cells. Sequence analysis revealed that the tev mRNA is generated by splicing to a novel exon located in the env region. This identifies a fourth class of multiply spliced human immunodeficiency virus mRNAs, produced in infected and transfected cells. tev is regulated during the virus life cycle similarly to the other regulatory proteins, tat, rev, and nef, and displays both tat and rev activities in functional assays. Since tev contains important functional domains of tat and rev and is produced very early after transfection, it may be an important regulator in the initial phase of virus expression. Another rev-related protein, p18(6)Drev, containing env and rev sequences, was characterized and was found not to have detectable rev activity. Images PMID:2186172

  5. Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine

    PubMed Central

    Chamcha, Venkateswarlu; Kannanganat, Sunil; Gangadhara, Sailaja; Nabi, Rafiq; Kozlowski, Pamela A.; Montefiori, David C.; LaBranche, Celia C.; Wrammert, Jens; Keele, Brandon F.; Balachandran, Harikrishnan; Sahu, Sujata; Lifton, Michelle; Santra, Sampa; Basu, Rahul; Moss, Bernard; Robinson, Harriet L.; Amara, Rama Rao

    2016-01-01

    Background. In this study, we analyzed the protective efficacy of a simian immunodeficiency virus (SIV) macaque 239 (SIVmac239) analogue of the clinically tested GOVX-B11 deoxyribonucleic acid (DNA)/modified vaccinia Ankara (MVA) human immunodeficiency virus vaccine. Methods. The tested vaccine used a DNA immunogen mutated to mimic the human vaccine and a regimen with DNA deliveries at weeks 0 and 8 and MVA deliveries at weeks 16 and 32. Twelve weekly rectal challenges with 0.3 animal infectious doses of SIV sootey mangabey E660 (SIVsmE660) were administered starting at 6 months after the last immunization. Results. Over the first 6 rectal exposures to SIVsmE660, <10-year-old tripartite motif-containing protein 5 (TRIM5)α-permissive rhesus macaques showed an 80% reduction in per-exposure risk of infection as opposed to a 46% reduction in animals over 10 years old; and, over the 12 challenges, they showed a 72% as opposed to a 10% reduction. Analyses of elicited immune responses suggested that higher antibody responses in the younger animals had played a role in protection. Conclusions. The simian analogue of the GOVX-B11 HIV provided strong protection against repeated rectal challenges in young adult macaques. PMID:27006959

  6. Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine.

    PubMed

    Chamcha, Venkateswarlu; Kannanganat, Sunil; Gangadhara, Sailaja; Nabi, Rafiq; Kozlowski, Pamela A; Montefiori, David C; LaBranche, Celia C; Wrammert, Jens; Keele, Brandon F; Balachandran, Harikrishnan; Sahu, Sujata; Lifton, Michelle; Santra, Sampa; Basu, Rahul; Moss, Bernard; Robinson, Harriet L; Amara, Rama Rao

    2016-01-01

    Background.  In this study, we analyzed the protective efficacy of a simian immunodeficiency virus (SIV) macaque 239 (SIVmac239) analogue of the clinically tested GOVX-B11 deoxyribonucleic acid (DNA)/modified vaccinia Ankara (MVA) human immunodeficiency virus vaccine. Methods.  The tested vaccine used a DNA immunogen mutated to mimic the human vaccine and a regimen with DNA deliveries at weeks 0 and 8 and MVA deliveries at weeks 16 and 32. Twelve weekly rectal challenges with 0.3 animal infectious doses of SIV sootey mangabey E660 (SIVsmE660) were administered starting at 6 months after the last immunization. Results.  Over the first 6 rectal exposures to SIVsmE660, <10-year-old tripartite motif-containing protein 5 (TRIM5)α-permissive rhesus macaques showed an 80% reduction in per-exposure risk of infection as opposed to a 46% reduction in animals over 10 years old; and, over the 12 challenges, they showed a 72% as opposed to a 10% reduction. Analyses of elicited immune responses suggested that higher antibody responses in the younger animals had played a role in protection. Conclusions.  The simian analogue of the GOVX-B11 HIV provided strong protection against repeated rectal challenges in young adult macaques. PMID:27006959

  7. 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

  8. 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

  9. 38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Disclosure of information 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...

  10. 38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Disclosure of information 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...

  11. 38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Disclosure of information 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...

  12. 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

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Disclosure of information 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...

  13. 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

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Disclosure of information 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...

  14. 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

  15. Interaction of Human Immunodeficiency Virus Type 2 Vpx and Invariant Chain

    PubMed Central

    Pancio, Heather A.; Vander Heyden, Nancy; Kosuri, Kavitha; Cresswell, Peter; Ratner, Lee

    2000-01-01

    Vpx is a virion-associated protein of human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency viruses. The yeast two-hybrid system was used to identify invariant chain (Ii) as a cellular protein that interacts with HIV-2 Vpx. Vpx-Ii interaction was confirmed in cell-free reactions using bacterially expressed glutathione S-transferase fusion proteins and by coimmunoprecipitation in transfected and infected cells. In chronically infected cells expressing Vpx, Ii levels were markedly decreased, presumably due to enhanced degradation. These findings suggest that Vpx may disrupt major histocompatibility complex class II antigen presentation. PMID:10846101

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

    PubMed

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

    2016-01-01

    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

  18. 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

  19. Optimization of Human Immunodeficiency Virus Treatment During Incarceration

    PubMed Central

    Meyer, Jaimie P.; Cepeda, Javier; Wu, Johnny; Trestman, Robert L.; Altice, Frederick L.; Springer, Sandra A.

    2014-01-01

    IMPORTANCE Human immunodeficiency virus (HIV) management in correctional settings is logistically feasible, but HIV-related outcomes before release have not been recently systematically examined. OBJECTIVE To evaluate HIV treatment outcomes throughout incarceration, including jail and prison. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of longitudinally linked demographic, pharmacy, and laboratory data on 882 prisoners within the Connecticut Department of Correction (2005–2012) with confirmed HIV infection, who were continually incarcerated 90 days or more, had at least 2 HIV-1 RNA and CD4 lymphocyte measurements, and were prescribed antiretroviral therapy. MAIN OUTCOMES AND MEASURES Three electronic databases (correctional, laboratory, and pharmacy) were integrated to assess HIV viral suppression (HIV-1 RNA levels, <400 copies/mL) on intake and release. Secondary outcomes were mean change in log-transformed HIV-1 RNA levels and mean change in CD4 lymphocyte count during incarceration. Demographic characteristics, prescribed pharmacotherapies, receipt of directly observed therapy, and duration of incarceration were analyzed as possible explanatory variables for HIV viral suppression in logistic regression models. RESULTS Among 882 HIV-infected prisoners with 1185 incarceration periods, mean HIV-1 RNA level decreased by 1.1 log10 and CD4 lymphocyte count increased by 98 cells/μL over time, with a higher proportion achieving viral suppression by release compared with entry (70.0% vs 29.8%; P < .001); 36.9% of antiretroviral therapy (ART) regimens were changed during incarceration. After adjusting for baseline HIV-1 RNA level, prerelease viral suppression correlated with female sex (adjusted odds ratio, 1.81; 95% CI, 1.26–2.59) and psychiatric disorder severity below the sample median (adjusted odds ratio, 1.50; 95% CI, 1.12–1.99), but not race/ethnicity, incarceration duration, ART regimen or dosing strategy, or directly observed therapy

  20. Chronic kidney disease in human immunodeficiency virus infection.

    PubMed

    Fabian, J; Katz, I; Gerntholtz, T; Goetsch, S; Naicker, S

    2007-06-01

    The number of people living with human immunodeficiency virus (HIV) worldwide was estimated to be 39.5 million in 2006, 2.6 million more than in 2004. The manifestations of HIV infection in the kidney are multiple and varied, highlighting the complexity of the disease process. There is a wide spectrum of renal disease that occurs in the course of HIV infection. Biopsy studies reveal varying frequencies of histological patterns. HIV-associated nephropathy (HIVAN) is most common. A biopsy study at Chris Baragwanath Hospital in Soweto, South Africa showed that HIVAN was present in 27% and immune complex disease in 21%. Han et al. studied HIV-positive patients in Durban, South Africa and screened for proteinuria, including microalbuminuria. They found persistent proteinuria in 6%; HIVAN in 21/30 (72.4%) and the prevalence of HIVAN in patients with persistent microalbuminuria was 85.7%. Studies in black patients have shown a higher prevalence of both severe glomerular lesions (focal glomerulosclerosis) and nephrotic range proteinuria with renal dysfunction in the presence of normo-hypotension. There have been no prospective randomised controlled studies with any form of therapy for HIVAN to date. Therapy of HIVAN has included corticosteroids, cyclosporine and antiretroviral therapy (ART). ART appears to be a logical choice in the management of HIV-associated renal disease. Regimens containing protease inhibitors have been shown to be associated with significant slowing of the decline in creatinine clearance. Both peritoneal dialysis and haemodialysis are appropriate treatment modalities for HIV-infected patients with end stage renal disease. The choice of dialysis modality between haemodialysis and peritoneal dialysis is not a factor in predicting survival, if patients are stable on ART. Preliminary short-term data in case reports and small cohorts of liver, kidney, and heart transplant recipients suggest that patient survival rates may be similar to those in HIV

  1. Tightly bound zinc in human immunodeficiency virus type 1, human T-cell leukemia virus type I, and other retroviruses.

    PubMed Central

    Bess, J W; Powell, P J; Issaq, H J; Schumack, L J; Grimes, M K; Henderson, L E; Arthur, L O

    1992-01-01

    Human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type I (HTLV-I) were purified by sucrose density gradient centrifugation in the presence of 1 mM EDTA. Pelleted gradient fractions were analyzed for total protein, total Gag capsid protein, and total zinc. Zinc was found to copurify and concentrate with the virus particles. Through successive cycles of resuspending in buffer containing EDTA and repelleting, the zinc content remained constant at about 1.7 mol of zinc per mol of Gag protein. Proteins from purified virus (HIV-1 and HTLV-I) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, blotted to polyvinylidene fluoride paper, and probed with 65ZnCl2. Viral nucleocapsid (NC) proteins (HIV-1 p7NC and HTLV-I p15NC) bound 65Zn2+. Other retroviruses, including simian immunodeficiency virus, equine infectious anemia virus, bovine leukemia virus, Moloney murine leukemia virus, mouse mammary tumor virus, and Mason-Pfizer monkey virus, were found to contain amounts of zinc per milligram of total protein similar to those found in HIV-1 and HTLV-I. Collectively, these data support the hypothesis that retroviral NC proteins function as zinc finger proteins in mature viruses. Images PMID:1731111

  2. Human immunodeficiency virus integrase inhibitors efficiently suppress feline immunodeficiency virus replication in vitro and provide a rationale to redesign antiretroviral treatment for feline AIDS

    PubMed Central

    Savarino, Andrea; Pistello, Mauro; D'Ostilio, Daniela; Zabogli, Elisa; Taglia, Fabiana; Mancini, Fabiola; Ferro, Stefania; Matteucci, Donatella; De Luca, Laura; Barreca, Maria Letizia; Ciervo, Alessandra; Chimirri, Alba; Ciccozzi, Massimo; Bendinelli, Mauro

    2007-01-01

    Background Treatment of feline immunodeficiency virus (FIV) infection has been hampered by the absence of a specific combination antiretroviral treatment (ART). Integrase strand transfer inhibitors (INSTIs) are emerging as a promising new drug class for HIV-1 treatment, and we evaluated the possibility of inhibiting FIV replication using INSTIs. Methods Phylogenetic analysis of lentiviral integrase (IN) sequences was carried out using the PAUP* software. A theoretical three-dimensional structure of the FIV IN catalytic core domain (CCD) was obtained by homology modeling based on a crystal structure of HIV-1 IN CCD. The interaction of the transferred strand of viral DNA with the catalytic cavity of FIV IN was deduced from a crystal structure of a structurally similar transposase complexed with transposable DNA. Molecular docking simulations were conducted using a genetic algorithm (GOLD). Antiviral activity was tested in feline lymphoblastoid MBM cells acutely infected with the FIV Petaluma strain. Circular and total proviral DNA was quantified by real-time PCR. Results The calculated INSTI-binding sites were found to be nearly identical in FIV and HIV-1 IN CCDs. The close similarity of primate and feline lentivirus IN CCDs was also supported by phylogenetic analysis. In line with these bioinformatic analyses, FIV replication was efficiently inhibited in acutely infected cell cultures by three investigational INSTIs, designed for HIV-1 and belonging to different classes. Of note, the naphthyridine carboxamide INSTI, L-870,810 displayed an EC50 in the low nanomolar range. Inhibition of FIV integration in situ was shown by real-time PCR experiments that revealed accumulation of circular forms of FIV DNA within cells treated with L-870,810. Conclusion We report a drug class (other than nucleosidic reverse transcriptase inhibitors) that is capable of inhibiting FIV replication in vitro. The present study helped establish L-870,810, a compound successfully tested in

  3. Disseminated cutaneous leishmaniasis resembling post-kala-azar dermal leishmaniasis caused by Leishmania donovani in three patients co-infected with visceral leishmaniasis and human immunodeficiency virus/acquired immunodeficiency syndrome in Ethiopia.

    PubMed

    Gelanew, Tesfaye; Hurissa, Zewdu; Diro, Ermias; Kassahun, Aysheshm; Kuhls, Katrin; Schönian, Gabriele; Hailu, Asrat

    2011-06-01

    We report paired strains of Leishmania parasites, one from the viscera and the other from skin lesions that were isolated from three patients with visceral leishmaniasis and disseminated cutaneous leishmaniasis that were co-infected with human immunodeficiency virus. The causative parasites were characterized by polymerase chain reaction-restriction length polymorphism of the ribosomal DNA internal transcribed spacer 1 and by a panel of multilocus microsatellite markers. We demonstrated that the causative agent was Leishmania donovani in all cases, irrespective of the phenotype of the disease. The paired strains from viscera and skin lesions of the same patients showed genetic identity across the 14 microsatellite markers investigated. These findings demonstrate that the skin lesions in these human immunodeficiency virus-positive patients with visceral leishmaniasis were caused by dissemination of viscerotropic L. donovani parasites as a consequence of severe immunosuppression. However, in all three patients, rapid clearance of the skin lesions was observed after antimonial therapy. PMID:21633027

  4. Hydroxychloroquine treatment of patients with human immunodeficiency virus type 1.

    PubMed

    Sperber, K; Louie, M; Kraus, T; Proner, J; Sapira, E; Lin, S; Stecher, V; Mayer, L

    1995-01-01

    Hydroxychloroquine (HCQ), an antimalarial agent used to treat patients with autoimmune diseases, has been shown to suppress human immunodeficiency virus type 1 (HIV-1) replication in vitro in T cells and monocytes by inhibiting posttranscriptional modification of the virus. These in vitro observations have been expanded into an in vivo study of HCQ as a potential anti-HIV-1 agent in HIV-1-infected patients. A randomized, double-blind, placebo-controlled clinical trial was conducted in 40 asymptomatic HIV-1-infected patients who had CD4+ counts between 200 and 500 cells/mm3. Patients were randomly assigned to receive either HCQ 800 mg/d or placebo for 8 weeks. Virologic and immunologic parameters, including HIV-1 ribonucleic acid (RNA) via use of polymerase chain reaction, viral culture, antigen and mitogen responses, and proinflammatory cytokine levels were measured at the beginning and end of the study. The amount of recoverable HIV-1 RNA in plasma declined significantly in the HCQ group over the 8-week period (P = 0.022), while it increased in the placebo group. The percentage of CD4+ T cells remained stable in the HCQ-treated group (18.1 +/- 9.2% before treatment vs 18.6 +/- 10.5% after treatment) and fell significantly in the placebo group (21 +/- 7% before treatment vs 19.3 +/- 6.3% after treatment; P = 0.032). However, this was not reflected as a change in absolute CD4+ counts for either group (HCQ, 262.8 +/- 166 cells/mm3 vs 251 +/- 163 cells/mm3; placebo, 312 +/- 121 cells/mm3 vs 321 +/- 124 cells/mm3). Mitogen- and antigen-specific responses remained constant in the HCQ group while T cell proliferative responses to Candida decreased in the placebo group (4.8 +/- 3.6 x 10(3) SI [stimulation index] vs 3.0 +/- 3.0 x 10(3) SI; P = 0.032). Lastly, serum interleukin 6 levels declined in the HCQ group (14.3 +/- 13.5 U/mL vs 12.0 +/- 16.7 U/mL; P = 0.023) but not in the placebo group (11.3 +/- 8.8 U/mL vs 7.0 +/- 11.7 U/mL); this was coincident with a decrease in

  5. Molecular Evolution Analysis of the Human Immunodeficiency Virus Type 1 Envelope in Simian/Human Immunodeficiency Virus-Infected Macaques: Implications for Challenge Dose Selection ▿

    PubMed Central

    Varela, Mariana; Landskron, Lisa; Lai, Rachel P. J.; McKinley, Trevelyan J.; Bogers, Willy M.; Verschoor, Ernst J.; Dubbes, Rob; Barnett, Susan W.; Frost, Simon D. W.; Heeney, Jonathan L.

    2011-01-01

    Since the demonstration that almost 80% of human immunodeficiency virus type 1 (HIV-1) infections result from the transmission of a single variant from the donor, biological features similar to those of HIV mucosal transmission have been reported for macaques inoculated with simian immunodeficiency virus (SIV). Here we describe the early diversification events and the impact of challenge doses on viral kinetics and on the number of variants transmitted in macaques infected with the chimeric simian/human immunodeficiency virus SHIVsf162p4. We show that there is a correlation between the dose administered and the number of variants transmitted and that certain inoculum variants are preferentially transmitted. This could provide insight into the viral determinants of transmission and could aid in vaccine development. Challenge through the mucosal route with high doses results in the transmission of multiple variants in all the animals. Such an unrealistic scenario could underestimate potential intervention measures. We thus propose the use of molecular evolution analysis to aid in the determination of challenge doses that better mimic the transmission dynamics seen in natural HIV-1 infection. PMID:21795341

  6. The Hepatitis B Virus Genotype Affects the Persistence of Viral Replication in Immunodeficient NOG Mice

    PubMed Central

    Yokoyama, Yoshinobu; Miyagi, Takuya; Hikita, Hayato; Yoshioka, Teppei; Mukai, Kaori; Nawa, Takatoshi; Sakamori, Ryotaro; Ohkawa, Kazuyoshi; Hiramatsu, Naoki; Takahashi, Takeshi; Suemizu, Hiroshi; Ryo, Akihide; Tatsumi, Tomohide; Takehara, Tetsuo

    2015-01-01

    Background & Aims At least eight genotypes of Hepatitis B virus (HBV) have been identified. HBV genotype C is the most common genotype in Japan, although the incidence of HBV genotype A is increasing. The reason underlying the differences in viral multiplication of the HBV genotypes is unclear, especially in vivo. The purpose of this study was to elucidate the differences in HBV load and the persistence of viremia in vivo between genotypes A and C. Methods Immunodeficient NOG mice were transfected by hydrodynamic injection with the HBV expression plasmids pHBA1.2 or pHBC1.2, which contain overlength (1.2-mer) copies of the genomes of HBV genotype A or C, respectively. Results One day after transfection, the number of HBcAg-positive hepatocytes and serum HBV DNA levels were similar between mice transfected with pHBA1.2 and pHBC1.2. Serum levels of HBV DNA, HBsAg and HBeAg in mice transfected with pHBA1.2 were maintained over 5 months. In contrast, those in mice with pHBC1.2 gradually decreased over time and reached undetectable levels within 3 months after transfection. HBcAg-stained hepatocytes were detected in mice transfected with pHBA1.2, but not pHBC1.2, 5 months post-transfection. Double-staining immunohistochemistry revealed that the number of cleaved caspase3-stained, HBcAg-positive hepatocytes in the pHBC1.2-transfected mice was higher than in the pHBA1.2-transfected mice 3 days post-transfection. Moreover, the plasmid DNA and covalently closed circular DNA levels were decreased in the livers of pHBC1.2-transfected mice. These results suggested that hepatocytes expressing HBV genotype C were eliminated by apoptosis in the absence of immune cells more often than in hepatocytes expressing HBV genotype A. Conclusions Immunodeficient mice transfected with HBV genotype A develop persistent viremia, whereas those transfected with HBV genotype C exhibit transient viremia accompanied by apoptosis of HBV-expressing hepatocytes. This differences may affect the

  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. 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

  9. 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

  10. 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

  11. Simian Immunodeficiency Virus Replicates to High Levels in Naturally Infected African Green Monkeys without Inducing Immunologic or Neurologic Disease

    PubMed Central

    Broussard, Suzanne R.; Staprans, Silvija I.; White, Robert; Whitehead, Evelyn M.; Feinberg, Mark B.; Allan, Jonathan S.

    2001-01-01

    African green monkeys can maintain long-term persistent infection with simian immunodeficiency viruses (SIVagm) without developing AIDS and thus provide an important model for understanding mechanisms of natural host resistance to disease. This study assessed the levels and anatomic distribution of SIVagm in healthy, naturally infected monkeys. Quantitative competitive reverse transcriptase PCR assays developed to measure SIVagm from two African green monkey subspecies demonstrated high levels of SIV RNA in plasma (>6 × 106 RNA copies/ml) in sabaeus and vervet monkeys. Infectious virus was readily recovered from plasma and peripheral blood mononuclear cells and shown to be highly cytopathic in human cell lines and macrophages. SIVagm DNA levels were highest in the gastrointestinal tract, suggesting that the gut is a major site for SIVagm replication in vivo. Appreciable levels of virus were also found within the brain parenchyma and the cerebrospinal fluid (CSF), with lower levels detected in peripheral blood cells and lymph nodes. Virus isolates from the CSF and brain parenchyma readily infected macrophages in culture, whereas lymph node isolates were more restricted to growth in human T-cell lines. Comparison of env V2-C4 sequences showed extensive amino acid diversity between SIVagm recovered from the central nervous system and that recovered from lymphoid tissues. Homology between brain and CSF viruses, macrophage tropism, and active replication suggest compartmentalization in the central nervous system without associated neuropathology in naturally infected monkeys. These studies provide evidence that the nonpathogenic nature of SIVagm in the natural host can be attributed neither to more effective host control over viral replication nor to differences in the tissue and cell tropism from those for human immunodeficiency virus type 1-infected humans or SIV-infected macaques. PMID:11160730

  12. 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

  13. Biophysical Characterization of Nucleophosmin Interactions with Human Immunodeficiency Virus Rev and Herpes Simplex Virus US11

    PubMed Central

    Nouri, Kazem; Moll, Jens M.; Milroy, Lech-Gustav; Hain, Anika; Dvorsky, Radovan; Amin, Ehsan; Lenders, Michael; Nagel-Steger, Luitgard; Howe, Sebastian; Smits, Sander H. J.; Hengel, Hartmut; Schmitt, Lutz; Münk, Carsten; Brunsveld, Luc; Ahmadian, Mohammad R.

    2015-01-01

    Nucleophosmin (NPM1, also known as B23, numatrin or NO38) is a pentameric RNA-binding protein with RNA and protein chaperon functions. NPM1 has increasingly emerged as a potential cellular factor that directly associates with viral proteins; however, the significance of these interactions in each case is still not clear. In this study, we have investigated the physical interaction of NPM1 with both human immunodeficiency virus type 1 (HIV-1) Rev and Herpes Simplex virus type 1 (HSV-1) US11, two functionally homologous proteins. Both viral proteins show, in mechanistically different modes, high affinity for a binding site on the N-terminal oligomerization domain of NPM1. Rev, additionally, exhibits low-affinity for the central histone-binding domain of NPM1. We also showed that the proapoptotic cyclic peptide CIGB-300 specifically binds to NPM1 oligomerization domain and blocks its association with Rev and US11. Moreover, HIV-1 virus production was significantly reduced in the cells treated with CIGB-300. Results of this study suggest that targeting NPM1 may represent a useful approach for antiviral intervention. PMID:26624888

  14. Lymphadenopathy in macaques experimentally infected with the simian immunodeficiency virus (SIV).

    PubMed Central

    Chalifoux, L. V.; Ringler, D. J.; King, N. W.; Sehgal, P. K.; Desrosiers, R. C.; Daniel, M. D.; Letvin, N. L.

    1987-01-01

    A T-cell tropic lentivirus of macaques the simian immunodeficiency virus (SIV), has morphologic, growth, and antigenic properties that indicate that it is related to the human immunodeficiency virus (HIV), the etiologic agent of the acquired immune deficiency syndrome (AIDS) in humans. Six juvenile macaques developed persistent lymphadenopathy (greater than 3 months in duration) after inoculation with SIV. The histologic appearance of the lymph nodes was characterized by marked follicular hyperplasia with abundant proliferative B cells infiltrating into the paracortex. The number of T8-positive lymphocytes equaled or exceeded the number of T4-positive lymphocytes in the paracortex. These findings, in association with immunologic abnormalities and a previously observed fatal immunodeficiency syndrome in SIV-infected macaques, provide further evidence of the importance of SIV-induced disease in macaques as a model for the study of AIDS. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:3037910

  15. 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

    2016-03-31

    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. PMID:27034392

  16. 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

  17. The human immunodeficiency virus preventive vaccine research at the French National Agency for acquired immunodeficiency syndrome research.

    PubMed

    Fischer, Elizabeth; Rieux, Véronique; Guillet, Jean-Gérard; Kazatchkine, Michel

    2005-02-01

    The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic is of unprecedented gravity and is spreading rapidly, notably in the most disadvantaged regions of the world. The search for a preventive vaccine is thus an absolute priority. For over 10 years the French National Agency for AIDS research (ANRS) has been committed to an original program combining basic science and clinical research. The HIV preventive vaccine research program run by the ANRS covers upstream research for the definition of immunogens, animal models, and clinical research to evaluate candidate vaccines. Most researchers in 2004 believe that it should be possible to obtain partial vaccine protection through the induction of a strong and multiepitopic cellular response. Since 1992, the ANRS has set up 15 phases I and II clinical trials in order to evaluate the safety and the capacity of the candidate vaccines for inducing cellular immune responses. The tested candidate vaccines were increasingly complex recombinant canarypox viruses (Alvac) containing sequences coding for certain viral proteins, utilized alone or combined with other immunogens (whole or truncated envelope proteins). ANRS has also been developing an original strategy based on the utilization of lipopeptides. These comprise synthetic fragments of viral proteins associated with lipids that facilitate the induction of a cellular immune response. These approaches promptly allowed the assessment of a prime-boost strategy combining a viral vector and lipopeptides. PMID:15867969

  18. 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

  19. Characterization of Clonality of Epstein-Barr Virus-Induced Human B Lymphoproliferative Disease in Mice with Severe Combined Immunodeficiency

    PubMed Central

    Nakamine, Hirokazu; Masih, Aneal S.; Okano, Motohiko; Taguchi, Yuichi; Pirruccello, Samuel J.; Davis, Jack R.; Mahloch, Mark L.; Beisel, Kirk W.; Kleveland, Kimberly; Sanger, Warren G.; Purtilo, David T.

    1993-01-01

    To improve the diagnostic accuracy and understanding of the pathogenesis of lymphoproliferative diseases (LPDs) occurring in immunosuppressed transplant recipients (post-transplantation LPD), clonality of Epstein-Barr virus-induced human LPDs in mice with severe combined immunodeficiency was examined by analyzing: 1) human immunoglobulin genes and their products, 2) the clonality of Epstein-Barr virus DNA, and 3) genetic alteration of c-myc or bcl-2 genes. A spectrum of clonality was found in the LPDs comparable with that reported for post-transplantation LPDs, although rearrangements of c-myc or bcl-2 genes were not detected. It is confirmed that this system is useful in terms of clonality for understanding the early phases in the pathogenesis of post-transplantation LPD or LPD in immune deficient patients. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5 PMID:8380952

  20. 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

  1. 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…

  2. 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

  3. The Connections between Childhood Sexual Abuse and Human Immunodeficiency Virus Infection: Implications for Interventions

    ERIC Educational Resources Information Center

    Tarakeshwar, Nalini; Fox, Ashley; Ferro, Carol; Khawaja, Shazia; Kochman, Arlene; Sikkema, Kathleen J.

    2005-01-01

    A qualitative study was conducted with 28 women who are human immunodeficiency virus (HIV)-positive and have experienced childhood sexual abuse (CSA) in order to examine (1) the challenges generated by the experience of sexual abuse and related coping strategies, (2) the impact of the HIV diagnosis on their coping strategies, and (3) the links…

  4. Intraoral herpes simplex virus infection in a patient with common variable immunodeficiency.

    PubMed

    Villa, Alessandro; Treister, Nathaniel S

    2013-10-01

    We report a challenging case of an atypical presentation of recrudescent herpes simplex virus infection in a patient with common variable immunodeficiency. Oral infections in immunosuppressed patients may present with unusual clinical features that can mimic non-infectious diseases. This report discusses the diagnostic steps necessary for definitive diagnosis and to guide appropriate and effective management. PMID:23933299

  5. 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…

  6. 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…

  7. 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

  8. 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

  9. 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

  10. 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

  11. Cell Cycle Arrest in G2/M Promotes Early Steps of Infection by Human Immunodeficiency Virus

    PubMed Central

    Groschel, Bettina; Bushman, Frederic

    2005-01-01

    We have identified four small molecules that boost transduction of cells by human immunodeficiency virus (HIV) and investigated their mechanism of action. These molecules include etoposide and camptothecin, which induce DNA damage by inhibiting religation of cleaved topoisomerase-DNA complexes, taxol, which interferes with the function of microtubules, and aphidicolin, which inhibits DNA polymerases. All four compounds arrest the cell cycle at G2/M, though in addition high concentrations of aphidicolin arrest in G1. We find that early events of HIV replication, including synthesis of late reverse transcription products, two-long terminal repeat circles, and integrated proviruses, were increased after treatment of cells with concentrations of each compound that arrested in G2/M. Stimulation was seen for both transformed cell lines (293T and HeLa cells) and primary cells (IMR90 lung fibroblasts). Arrest in G1 with high concentrations of aphidicolin boosted transduction, though not much as with lower concentrations that arrested in G2/M. Arrest of IMR90 cells in G1 by serum starvation and contact inhibition reduced transduction. Previously, the proteasome inhibitor MG132 was reported to increase HIV infection—here we investigated the effects of combinations of the cell cycle inhibitors with MG132 and obtained data suggesting that MG132 may also boost transduction by causing G2/M cell cycle arrest. These data document that cell cycle arrest in G2/M boosts the early steps of HIV infection and suggests methods for increasing transduction with HIV-based vectors. PMID:15827184

  12. 5-Azacytidine Can Induce Lethal Mutagenesis in Human Immunodeficiency Virus Type 1▿ †

    PubMed Central

    Dapp, Michael J.; Clouser, Christine L.; Patterson, Steven; Mansky, Louis M.

    2009-01-01

    Ribonucleosides inhibit human immunodeficiency virus type 1 (HIV-1) replication by mechanisms that have not been fully elucidated. Here, we report the antiviral mechanism for the ribonucleoside analog 5-azacytidine (5-AZC). We hypothesized that the anti-HIV-1 activity of 5-AZC was due to an increase in the HIV-1 mutation rate following its incorporation into viral RNA during transcription. However, we demonstrate that 5-AZC's primary antiviral activity can be attributed to its effect on the early phase of HIV-1 replication. Furthermore, the antiviral activity was associated with an increase in the frequency of viral mutants, suggesting that 5-AZC's primary target is reverse transcription. Sequencing analysis showed an enrichment in G-to-C transversion mutations and further supports the idea that reverse transcription is an antiviral target of 5-AZC. These results indicate that 5-AZC is incorporated into viral DNA following reduction to 5-aza-2′-deoxycytidine. Incorporation into the viral DNA leads to an increase in mutant frequency that is consistent with lethal mutagenesis during reverse transcription as the primary antiviral mechanism of 5-AZC. Antiviral activity and increased mutation frequency were also associated with the late phase of HIV-1 replication; however, 5-AZC's effect on the late phase was less robust. These results reveal that the primary antiviral mechanism of 5-AZC can be attributed to its ability to increase the HIV-1 mutation frequency through viral-DNA incorporation during reverse transcription. Our observations indicate that 5-AZC can affect two steps in HIV-1 replication (i.e., transcription and reverse transcription) but that its primary antiviral activity is due to incorporation during reverse transcription. PMID:19726509

  13. Effect of 3'-azido-3'-deoxythymidine on human immunodeficiency virus type 1 replication in human fetal brain macrophages.

    PubMed Central

    Geleziunas, R; Arts, E J; Boulerice, F; Goldman, H; Wainberg, M A

    1993-01-01

    We investigated whether cells derived from the fetal central nervous system can support productive infection by a human immunodeficiency virus type 1 (HIV-1) isolate termed UHC-1, produced by a cellular clone derived from HIV-1 strain HIV-IIIB chronically infected U-937 promonocytic cells, and what the effect of nucleoside analogs might be on viral replication in this system. Fractionation of human fetal brain tissue into two different populations, enriched for either astrocytes or macrophages, showed that only the latter were able to support productive UHC-1 replication and generation of detectable progeny virus. Pretreatment of fetal brain macrophages with either of two nucleoside analogs, 3'-azido-3'-deoxythymidine (AZT) or the (-) enantiomer of 2'-deoxy-3'-thiacytidine, efficiently blocked production of progeny virus. Generation of unintegrated proviral DNA and HIV-1 transcripts were inhibited by pretreatment of fetal brain macrophages with 1 microM AZT. Administration of AZT at 24 h postinfection led to a slight reduction in viral transcript levels and viral progeny production by day 15 postinfection; however, brain macrophages under these conditions did not contain detectable amounts of unintegrated viral DNA. These results suggest that AZT may interfere with the accumulation of unintegrated HIV-1 DNA in brain macrophages. This is the first demonstration that nucleoside analogs are able to block HIV-1 replication in primary cultures of brain cells. Images PMID:8392310

  14. 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

  15. 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

  16. Intracellular Immunization of Human Fetal Cord Blood Stem/Progenitor Cells with a Ribozyme Against Human Immunodeficiency Virus Type 1

    NASA Astrophysics Data System (ADS)

    Yu, Mang; Leavitt, Mark C.; Maruyama, Midori; Yamada, Osamu; Young, Dennis; Ho, Anthony D.; Wong-Staal, Flossie

    1995-01-01

    Successful treatment of human immunodeficiency virus infection may ultimately require targeting of hematopoietic stem cells. Here we used retroviral vectors carrying the ribozyme gene to transduce CD34^+ cells from human fetal cord blood. Transduction and ribozyme expression had no apparent adverse effect on cell differentiation and/or proliferation. The macrophage-like cells, differentiated from the stem/progenitor cells in vitro, expressed the ribozyme gene and resisted infection by a macrophage tropic human immunodeficiency virus type 1. These results suggest the feasibility of stem cell gene therapy for human immunodeficiency virus-infected patients.

  17. In Vitro Characterization of a Simian Immunodeficiency Virus-Human Immunodeficiency Virus (HIV) Chimera Expressing HIV Type 1 Reverse Transcriptase To Study Antiviral Resistance in Pigtail Macaques

    PubMed Central

    Ambrose, Zandrea; Boltz, Valerie; Palmer, Sarah; Coffin, John M.; Hughes, Stephen H.; KewalRamani, Vineet N.

    2004-01-01

    Antiviral resistance is a significant obstacle in the treatment of human immunodeficiency virus type 1 (HIV-1)-infected individuals. Because nonnucleoside reverse transcriptase inhibitors (NNRTIs) specifically target HIV-1 reverse transcriptase (RT) and do not effectively inhibit simian immunodeficiency virus (SIV) RT, the development of animal models to study the evolution of antiviral resistance has been problematic. To facilitate in vivo studies of NNRTI resistance, we examined whether a SIV that causes immunopathogenesis in pigtail macaques could be made sensitive to NNRTIs. Two simian-human immunodeficiency viruses (SHIVs) were derived from the genetic background of SIVmne: SIV-RT-YY contains RT substitutions intended to confer NNRTI susceptibility (V181Y and L188Y), and RT-SHIVmne contains the entire HIV-1 RT coding region. Both mutant viruses grew to high titers in vitro but had reduced fitness relative to wild-type SIVmne. Although the HIV-1 RT was properly processed into p66 and p51 subunits in RT-SHIVmne particles, the RT-SHIVmne virions had lower levels of RT per viral genomic RNA than HIV-1. Correspondingly, there was decreased RT activity in RT-SHIVmne and SIV-RT-YY particles. HIV-1 and RT-SHIVmne were similarly susceptible to the NNRTIs efavirenz, nevirapine, and UC781. However, SIV-RT-YY was less sensitive to NNRTIs than HIV-1 or RT-SHIVmne. Classical NNRTI resis tance mutations were selected in RT-SHIVmne after in vitro drug treatment and were monitored in a sensitive allele-specific real-time RT-PCR assay. Collectively, these results indicate that RT-SHIVmne may be a useful model in macaques for the preclinical evaluation of NNRTIs and for studies of the development of drug resistance in vivo. PMID:15564466

  18. Chromosomal radiosensitivity of human immunodeficiency virus positive/negative cervical cancer patients in South Africa

    PubMed Central

    HERD, OLIVIA; FRANCIES, FLAVIA; KOTZEN, JEFFREY; SMITH, TRUDY; NXUMALO, ZWIDE; MULLER, XANTHENE; SLABBERT, JACOBUS; VRAL, ANNE; BAEYENS, ANS

    2016-01-01

    Cervical cancer is the second most common cancer amongst South African women and is the leading cause of cancer-associated mortality in this region. Several international studies on radiation-induced DNA damage in lymphocytes of cervical cancer patients have remained inconclusive. Despite the high incidence of cervical cancer in South Africa, and the extensive use of radiotherapy to treat it, the chromosomal radiosensitivity of South African cervical cancer patients has not been studied to date. Since a high number of these patients are human immunodeficiency virus (HIV)-positive, the effect of HIV infection on chromosomal radiosensitivity was also investigated. Blood samples from 35 cervical cancer patients (20 HIV-negative and 15 HIV-positive) and 20 healthy controls were exposed to X-rays at doses of 6 MV of 2 and 4 Gy in vitro. Chromosomal radiosensitivity was assessed using the micronucleus (MN) assay. MN scores were obtained using the Metafer 4 platform, an automated microscopic system. Three scoring methods of the MNScore module of Metafer were applied and compared. Cervical cancer patients had higher MN values than healthy controls, with HIV-positive patients having the highest MN values. Differences between groups were significant when using a scoring method that corrects for false positive and false negative MN. The present study suggested increased chromosomal radiosensitivity in HIV-positive South African cervical cancer patients. PMID:26549042

  19. Discovery of novel ribonucleoside analogs with activity against human immunodeficiency virus type 1.

    PubMed

    Dapp, Michael J; Bonnac, Laurent; Patterson, Steven E; Mansky, Louis M

    2014-01-01

    Reverse transcription is an important early step in retrovirus replication and is a key point targeted by evolutionarily conserved host restriction factors (e.g., APOBEC3G, SamHD1). Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a major target of antiretroviral drugs, and concerns regarding drug resistance and off-target effects have led to continued efforts for identifying novel approaches to targeting HIV-1 RT. Several observations, including those obtained from monocyte-derived macrophages, have argued that ribonucleotides and their analogs can, intriguingly, impact reverse transcription. For example, we have previously demonstrated that 5-azacytidine has its greatest antiviral potency during reverse transcription by enhancement of G-to-C transversion mutations. In the study described here, we investigated a panel of ribonucleoside analogs for their ability to affect HIV-1 replication during the reverse transcription process. We discovered five ribonucleosides-8-azaadenosine, formycin A, 3-deazauridine, 5-fluorocytidine, and 2'-C-methylcytidine-that possess anti-HIV-1 activity, and one of these (i.e., 3-deazauridine) has a primary antiviral mechanism that involves increased HIV-1 mutational loads, while quantitative PCR analysis determined that the others resulted in premature chain termination. Taken together, our findings provide the first demonstration of a series of ribonucleoside analogs that can target HIV-1 reverse transcription with primary antiretroviral mechanisms that include premature termination of viral DNA synthesis or enhanced viral mutagenesis. PMID:24155391

  20. 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

  1. 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

  2. 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. PMID:25913034

  3. Trichosanthin inhibits integration of human immunodeficiency virus type 1 through depurinating the long-terminal repeats.

    PubMed

    Zhao, Wen-Long; Feng, Du; Wu, Ju; Sui, Sen-Fang

    2010-04-01

    Trichosanthin (TCS) is a type I ribosome-inactivating protein with potent inhibitory activity against human immunodeficiency virus type 1. However, the anti-viral mechanism remains elusive. By a well-accepted HIV-1 integration assay, we demonstrated that TCS prevents HIV-1 DNA integration in a dose dependent manner in cell culture. At the same condition, TCS fails to induce obvious cytotoxicity and is also unable to interference viral early events such as viral entry, uncoating or reverse transcription. The HIV-1 integrase can integrate HIV-1 long-terminal repeats into cellular chromosome. The interaction of TCS with these viral integration components was also examined, indicating that TCS does not interact with HIV-1 integrase by the GST-pull down assay, but binds to the long terminal repeats in a transient manner. We further revealed that TCS can efficiently depurinate HIV-1 long-terminal repeats, which may be responsible for the inhibitory activity on HIV-1 integration. In conclusion, we elucidated that TCS specifically inhibits HIV-1 integration by depurinating the long-terminal repeats. PMID:19669933

  4. 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

  5. Human immunodeficiency virus and hepatitis C virus testing services at syringe exchange programs: availability and outcomes.

    PubMed

    Heinzerling, Keith G; Kral, Alex H; Flynn, Neil M; Anderson, Rachel L; Scott, Andrea; Gilbert, Mary L; Asch, Steven M; Bluthenthal, Ricky N

    2007-06-01

    We described the availability and outcomes of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) testing services at syringe exchange programs throughout California, using interviews with 24 syringe exchange program directors and 560 syringe exchange clients. Both HIV and HCV testing services were available in 62% of programs, 21% had HIV testing only, and 17% had neither. Programs administered by health care/social service providers were more likely than independent syringe exchange programs to have HIV and HCV testing services available. Among clients of programs with testing available, clients of illegal programs were significantly less likely than clients of legal programs to have used syringe exchange HIV and HCV testing services. The availability of HIV and HCV testing services at syringe exchange programs varies, and the use of existing testing services by clients is not universal. Efforts to increase both the availability of HIV and HCV testing services at syringe exchange programs and the use of existing testing services are needed. PMID:17481466

  6. 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

  7. 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

  8. Liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfection: Diagnostic methods and clinical impact.

    PubMed

    Sagnelli, Caterina; Martini, Salvatore; Pisaturo, Mariantonietta; Pasquale, Giuseppe; Macera, Margherita; Zampino, Rosa; Coppola, Nicola; Sagnelli, Evangelista

    2015-10-28

    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

  9. 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

  10. 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

  11. Topoisomerase I activity associated with human immunodeficiency virus (HIV) particles and equine infectious anemia virus core.

    PubMed Central

    Priel, E; Showalter, S D; Roberts, M; Oroszlan, S; Segal, S; Aboud, M; Blair, D G

    1990-01-01

    In the present study, we found a topoisomerase I (topo I) activity in two strains of human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV) particles. The topo I activity was located in the EIAV cores and differed from the cellular topo I in its ionic requirements and response to ATP, indicating that these were two distinct forms of this enzyme. Topo I activity was removed from the viral lysates and viral cores by anti-topo I antiserum. The only protein recognized by this antiserum was an 11.5 kd protein in HIV lysate and 11 kd in EIAV lysate. We showed that the 11 kd protein recognized by the anti-topo I antiserum is the EIAV p11 nucleocapsid protein. Furthermore, purified topo I protein blocked the binding of the antibodies to the p11 protein and vice versa, purified p11 protein blocked the binding of these antibodies to the cellular topo I. These results suggest that the EIAV p11 nucleocapsid protein and the cellular topo I share similar epitopes. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. PMID:2174357

  12. Hepatitis C virus and human immunodeficiency virus transmission routes: Differences and similarities.

    PubMed

    Cainelli, Francesca

    2013-05-27

    Bouare et al found that hepatitis C virus (HCV) infection in Malian women is mainly transmitted through medical procedures with contaminated supplies, and that human immunodeficiency virus (HIV) transmission is predominantly sexual. The results of this study confirm those of a recent case-control study in New York and Oregon which demonstrated that healthcare exposures represent an important source of new HCV infections in United States. HCV seroprevalence was only 0.2% in pregnant, young Malian women, indicating that hygiene improved in healthcare facilities over time. Heterosexual transmission of HCV is exceptional, and can occur, from males to females, in extremely rare occasions in case of vaginal mucosal damage or less rarely through anal intercourse. The Malian study did not show an association between HIV infection and hospitalization, transfusion, tattoo, dental care. Transmission by needle-stick injury occurs in 0.9%-2.2% of exposures from HCV-infected subjects and in 0.1%-0.3% of exposures from HIV-infected individuals. HCV is therefore more transmissible through percutaneous exposure. PMID:23717734

  13. Quality of life among human immunodeficiency virus-1 infected and human immunodeficiency virus-1/hepatitis C virus co-infected individuals in Iranian patients

    PubMed Central

    Sabouri, Sarah; Delavar, Ali; Jabbari, Hossain

    2016-01-01

    Background: The aim of this study was to compare the quality of life (QOL) of people infected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV). The study design was a cross sectional descriptive survey, using self administered questionnaires. Materials and Methods: A convenience sample of 242 patients (131 of them HIV/HCV), Iranian adults (aged 18–57) living with HIV/AIDS, was recruited from outpatient referring to Imam Khomeini Hospital behavioral counseling center in Tehran city, Iran. The instruments included the Multidimensional QOL HIV (MQoL HIV) and a demographic section. Results: The majority of the samples were male and single. The mean age was 36.52 years (standard deviation = 8.5). HIV mono infected patients reported higher scores in social support and physical functioning, but lower scores in physical health compared with HIV/HCV co infected individuals. There was no significant difference in overall MQOL HIV score between HIV and HIV/HCV patients. Conclusion: Future studies will need to explore the impact of HCV on HIV infected individuals' QOL.

  14. 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

  15. A Dominant Role for CD8+-T-Lymphocyte Selection in Simian Immunodeficiency Virus Sequence Variation†

    PubMed Central

    O'Connor, David H.; McDermott, Adrian B.; Krebs, Kendall C.; Dodds, Elizabeth J.; Miller, Jacqueline E.; Gonzalez, Edna J.; Jacoby, Timothy J.; Yant, Levi; Piontkivska, Helen; Pantophlet, Ralph; Burton, Dennis R.; Rehrauer, William M.; Wilson, Nancy; Hughes, Austin L.; Watkins, David I.

    2004-01-01

    CD8+ T lymphocytes (CD8-TL) select viral escape variants in both human immunodeficiency virus and simian immunodeficiency virus (SIV) infections. The frequency of CD8-TL viral escape as well as the contribution of escape to overall virus diversification has not been assessed. We quantified CD8-TL selection in SIV infections by sequencing viral genomes from 35 SIVmac239-infected animals at the time of euthanasia. Here we show that positive selection for sequences encoding 46 known CD8-TL epitopes is comparable to the positive selection observed for the variable loops of env. We also found that >60% of viral variation outside of the viral envelope occurs within recognized CD8-TL epitopes. Therefore, we conclude that CD8-TL selection is the dominant cause of SIV diversification outside of the envelope. PMID:15564508

  16. Trans-activation of human immunodeficiency virus gene expression is mediated by nuclear events

    SciTech Connect

    Hauber, J.; Perkins, A.; Heimer, E.P.; Cullen, B.R.

    1987-09-01

    Human immunodeficiency virus encodes a gene product termed tat that is able to activate viral gene expression when present in trans. The mechanism of action of the tat gene product appears to be bimodal, resulting in both an increase in the steady-state level of viral mRNA and the enhanced translation of that RNA. In this report, the authors have examined the mechanism by which tat elevates viral mRNA levels. Data are presented demonstrating that tat acts by increasing the rate of viral transcription, rather than by modulating the stability of viral mRNA. Indirect immunofluorescence was used to show that tat is predominantly localized in the nucleus of expressing cells, a location consistent with a role in the regulation of viral transcription. These results suggest that tat could play a role in human immunodeficiency virus replication essentially similar to that proposed for the trans-acting nuclear gene products described for several other virus species.

  17. Reciprocal modulations between p53 and Tat of human immunodeficiency virus type 1.

    PubMed Central

    Li, C J; Wang, C; Friedman, D J; Pardee, A B

    1995-01-01

    Infection by human immunodeficiency virus type 1 (HIV-1) causes acquired immunodeficiency syndrome (AIDS) after a long clinical latency. This disease is associated with a spectrum of cancers. Here we report that wild-type p53 is a potent suppressor of Tat, a major transactivator of HIV-1. Reciprocally, Tat inhibits the transcription of p53. Downregulation of p53 by upregulated tat may be important for the establishment of productive viral infection in a cell and also may be involved in the development of AIDS-related malignancies. Images Fig. 2 Fig. 3 Fig. 4 PMID:7777531

  18. Purinergic signaling and human immunodeficiency virus/acquired immune deficiency syndrome: From viral entry to therapy

    PubMed Central

    Passos, Daniela F; Schetinger, Maria Rosa C; Leal, Daniela BR

    2015-01-01

    Human immunodeficiency virus (HIV) infection is a serious condition associated to severe immune dysfunction and immunodeficiency. Mechanisms involved in HIV-associated immune activation, inflammation and loss of CD4+ T cells have been extensively studied, including those concerning purinergic signaling pathways. Purinergic signaling components are involved in viral entry and replication and disease progression. Research involving the participation of purinergic signaling in HIV infection has been not only important to elucidate disease mechanisms but also to introduce new approaches to therapy. The involvement of purinergic signaling in the pathogenesis of HIV infection and its implications in the control of the HIV infection are reviewed in this paper. PMID:26279989

  19. 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

  20. Human immunodeficiency virus type 1 LTR TATA and TAR region sequences required for transcriptional regulation.

    PubMed Central

    Garcia, J A; Harrich, D; Soultanakis, E; Wu, F; Mitsuyasu, R; Gaynor, R B

    1989-01-01

    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

  1. Triterpene derivatives that block entry of human immunodeficiency virus type 1 into cells.

    PubMed Central

    Mayaux, J F; Bousseau, A; Pauwels, R; Huet, T; Hénin, Y; Dereu, N; Evers, M; Soler, F; Poujade, C; De Clercq, E

    1994-01-01

    A series of triterpene compounds characterized by a stringent structure-activity relationship were identified as potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication. Currently studied botulinic derivatives have 50% inhibitory concentrations (IC50) against HIV-1 strain IIIB/LAI in the 10 nM range in several cellular infection assays but are inactive against HIV-2. These compounds did not significantly inhibit the in vitro activities of several purified HIV-1 enzymes. Rather, they appeared to block virus infection at a postbinding, envelope-dependent step involved in the fusion of the virus to the cell membrane. PMID:8170948

  2. Role of human immunodeficiency virus type 1 integrase in uncoating of the viral core.

    PubMed

    Briones, Marisa S; Dobard, Charles W; Chow, Samson A

    2010-05-01

    After membrane fusion with a target cell, the core of human immunodeficiency virus type 1 (HIV-1) enters into the cytoplasm, where uncoating occurs. The cone-shaped core is composed of the viral capsid protein (CA), which disassembles during uncoating. The underlying factors and mechanisms governing uncoating are poorly understood. Several CA mutations can cause changes in core stability and a block at reverse transcription, demonstrating the requirement for optimal core stability during viral replication. HIV-1 integrase (IN) catalyzes the insertion of the viral cDNA into the host genome, and certain IN mutations are pleiotropic. Similar to some CA mutants, two IN mutants, one with a complete deletion of IN (NL-DeltaIN) and the other with a Cys-to-Ser substitution (NL-C130S), were noninfectious, with a replication block at reverse transcription. Compared to the wild type (WT), the cytoplasmic CA levels of the IN mutants in infected cells were reduced, suggesting accelerated uncoating. The role of IN during uncoating was examined by isolating and characterizing cores from NL-DeltaIN and NL-C130S. Both IN mutants could form functional cores, but the core yield and stability were decreased. Also, virion incorporation of cyclophilin A (CypA), a cellular peptidyl-prolyl isomerase that binds specifically to CA, was decreased in the IN mutants. Cores isolated from WT virus depleted of CypA had an unstable-core phenotype, confirming a role of CypA in promoting optimal core stability. Taken together, our results indicate that IN is required during uncoating for maintaining CypA-CA interaction, which promotes optimal stability of the viral core. PMID:20219923

  3. IL-4 increases Simian immunodeficiency virus replication despite enhanced SIV immune responses in infected rhesus macaques.

    PubMed

    Boyer, J D; Nath, B; Schumann, K; Curley, E; Manson, K; Kim, J; Weiner, D B

    2002-05-01

    It is widely believed that a Th1 type CD4 response is critical for enhancement of CD8 immunity and for controlling HIV-1 infection. Th2 type responses, such as what might be seen in a chronic parasitic infection, would sacrifice cellular immunity and thus benefit the virus at the expense of the host. However, there has been little direct examination of the hypothesis in a primate model system. Accordingly, the simian immunodeficiency virus (SIV) infected rhesus macaque model was used to investigate the impact of immunisation with SIV expressing DNA constructs and co-injection with IL-4 on the SIV specific immunological responses, lymphocyte cell counts, as well as the impact on viral load. IL-4 is a Th2 type cytokine, which enhances antibody production and inhibits a CD4 Th1 phenotype. Rhesus macaques were infected with 10 AID50 of SIVmac239 and treated with 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) 9 weeks post-infection. During PMPA treatment, animals were immunised with plasmids that expressed the SIV proteins, env, rev, gag and pol. In addition, they were immunised with a construct that encoded the gene for IL-4. IL-4 co-immunisation increased the neutralizing antibody titres in this group. Importantly, the viral loads in animals vaccinated with IL-4 expressing plasmid increased during the immunisation regimens despite the higher neutralizing antibody titres. In addition, neutralizing antibodies did not correlate with viral set point prior to PMPA treatment, however, there was a correlation between viral loads and antibody titres following the treatment with PMPA. Antibody titres decreased following the suppression of viral load. Importantly, vaccination in the absence of IL-4 protected CD4 levels without increasing viral load. The data support the hypothesis that inappropriate immune bias toward a Th2 pathway would ultimately enhance disease progression. PMID:11943227

  4. Determinants of the establishment of human immunodeficiency virus type 1 latency.

    PubMed

    Duverger, Alexandra; Jones, Jennifer; May, Jori; Bibollet-Ruche, Frederic; Wagner, Frederic A; Cron, Randall Q; Kutsch, Olaf

    2009-04-01

    Recent research has emphasized the notion that human immunodeficiency virus type 1 (HIV-1) latency is controlled by a restrictive histone code at, or DNA methylation of, the integrated viral promoter (long terminal repeat [LTR]). The present concept of HIV-1 latency has essentially been patterned from the principles of cellular gene regulation. Here we introduce an experimental system that allows for the qualitative and quantitative kinetic study of latency establishment and maintenance at the population level. In this system, we find no evidence that HIV-1 latency establishment is the consequence of downregulation of initial active infection followed by the establishment of a restrictive histone code at the viral LTR. Latent infection was established following integration of the virus in the absence of viral gene expression (silent integration) and was a function of the NF-kappaB activation level in the host cell at the time of infection. In the absence of a role for epigenetic regulation, we demonstrate that transcriptional interference, a mechanism that has recently been suggested to add to the stabilization of HIV-1 latency, is the primary mechanism to govern latency maintenance. These findings provide direct experimental evidence that the high number of viral integration events (>90%) found in actively expressed genes of CD4(+) memory T cells from highly active antiretroviral therapy-suppressed patients represent indeed latent infection events and that transcriptional interference may be the primary mechanism to control HIV-1 latency in vivo. HIV-1 latency may thus not be governed by the principles of cellular gene regulation, and therapeutic strategies to deplete the pool of latently HIV-1-infected cells should be reconsidered. PMID:19144703

  5. Determinants of the Establishment of Human Immunodeficiency Virus Type 1 Latency▿

    PubMed Central

    Duverger, Alexandra; Jones, Jennifer; May, Jori; Bibollet-Ruche, Frederic; Wagner, Frederic A.; Cron, Randall Q.; Kutsch, Olaf

    2009-01-01

    Recent research has emphasized the notion that human immunodeficiency virus type 1 (HIV-1) latency is controlled by a restrictive histone code at, or DNA methylation of, the integrated viral promoter (long terminal repeat [LTR]). The present concept of HIV-1 latency has essentially been patterned from the principles of cellular gene regulation. Here we introduce an experimental system that allows for the qualitative and quantitative kinetic study of latency establishment and maintenance at the population level. In this system, we find no evidence that HIV-1 latency establishment is the consequence of downregulation of initial active infection followed by the establishment of a restrictive histone code at the viral LTR. Latent infection was established following integration of the virus in the absence of viral gene expression (silent integration) and was a function of the NF-κB activation level in the host cell at the time of infection. In the absence of a role for epigenetic regulation, we demonstrate that transcriptional interference, a mechanism that has recently been suggested to add to the stabilization of HIV-1 latency, is the primary mechanism to govern latency maintenance. These findings provide direct experimental evidence that the high number of viral integration events (>90%) found in actively expressed genes of CD4+ memory T cells from highly active antiretroviral therapy-suppressed patients represent indeed latent infection events and that transcriptional interference may be the primary mechanism to control HIV-1 latency in vivo. HIV-1 latency may thus not be governed by the principles of cellular gene regulation, and therapeutic strategies to deplete the pool of latently HIV-1-infected cells should be reconsidered. PMID:19144703

  6. South Asian Consensus Guidelines for the rational management of diabetes in human immunodeficiency virus/acquired immunodeficiency syndrome

    PubMed Central

    Kalra, Sanjay; Unnikrishnan, Ambika Gopalakrishnan; Raza, Syed Abbas; Bantwal, Ganpathy; Baruah, Manash P.; Latt, Tint Swe; Shrestha, Dina; John, Mathew; Katulanda, Prasad; Somasundaram, Noel; Sahay, Rakesh; Pathan, Faruque

    2011-01-01

    As newer methods of management are made available, and accessible, survival rates with human immunodeficiency virus (HIV) are increasing. This means that chronic, metabolic complications of HIV are becoming more frequent in clinical practice, as acute morbidity is controlled. Management of HIV/acquired immunodeficiency syndrome (AIDS) is gradually expanding to include these chronic and metabolic complications of the disease, and the adverse effects associated with its treatments, including diabetes. Unfortunately, no guidelines are available to help the medical practitioners choose appropriate therapy for patients with these conditions. The aim of the South Asian Consensus Guidelines is to provide evidence-based recommendations to assist healthcare providers in the rational management of type 2 diabetes mellitus in patients with HIV. The development of these guidelines used systematic reviews of available evidence to form its key recommendations. These guidelines and associated review of literature represent a compilation of available knowledge regarding rational management of diabetes in HIV. Patients of diabetes with concomitant HIV infection are managed optimally with insulin therapy and judicious use of highly active antiretroviral therapy with suitable alternatives is also recommended. These guidelines should prove helpful to physicians, not only in South Asia, but also across the globe, while managing patients with coexistent HIV and diabetes. PMID:22028994

  7. 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

  8. Modulation by Morphine of Viral Set Point in Rhesus Macaques Infected with Simian Immunodeficiency Virus and Simian-Human Immunodeficiency Virus

    PubMed Central

    Kumar, Rakesh; Torres, Cynthia; Yamamura, Yasuhiro; Rodriguez, Idia; Martinez, Melween; Staprans, Silvija; Donahoe, Robert M.; Kraiselburd, Edmundo; Stephens, Edward B.; Kumar, Anil

    2004-01-01

    Six rhesus macaques were adapted to morphine dependence by injecting three doses of morphine (5 mg/kg of body weight) for a total of 20 weeks. These animals along with six control macaques were infected intravenously with mixture of simian-human immunodeficiency virus KU-1B (SHIVKU-1B), SHIV89.6P, and simian immunodeficiency virus 17E-Fr. Levels of circulating CD4+ T cells and viral loads in the plasma and the cerebrospinal fluid were monitored in these macaques for a period of 12 weeks. Both morphine and control groups showed precipitous loss of CD4+ T cells. However this loss was more prominent in the morphine group at week 2 (P = 0.04). Again both morphine and control groups showed comparable peak plasma viral load at week 2, but the viral set points were higher in the morphine group than that in the control group. Likewise, the extent of virus replication in the cerebral compartment was more pronounced in the morphine group. These results provide a definitive evidence for a positive correlation between morphine and levels of viral replication. PMID:15452267

  9. 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

  10. Human immunodeficiency virus type 1 integrase: effect on viral replication of mutations at highly conserved residues.

    PubMed

    Cannon, P M; Wilson, W; Byles, E; Kingsman, S M; Kingsman, A J

    1994-08-01

    Sequence comparisons of the integrase (IN) proteins from different retroviruses have identified several highly conserved residues. We have introduced mutations at 16 of these sites into the integrase gene of human immunodeficiency virus type 1 and analyzed the phenotypes of the resulting viruses. The viruses were all normal for p24 content and reverse transcriptase activity. In addition, all of the mutants could infect T-cell lines and undergo reverse transcription, as assessed by PCR analysis. Most of the mutant viruses also had normal Western blot (immunoblot) profiles, although three of the mutations resulted in reduced signals for IN relative to the wild type on the immunoblots and mutation of residue W235 completely abolished recognition of the protein by pooled sera from human immunodeficiency virus type 1-positive patients. Mutations that have previously been shown to abolish activity in in vitro studies produced noninfectious viruses. The substitution of W235 was notable in producing a noninfectious virus, despite previous reports of this residue being nonessential for IN activity in vitro (A.D. Leavitt, L. Shiue, and H.E. Varmus, J. Biol. Chem. 268:2113-2119, 1993). In addition, we have identified four highly conserved residues that can be mutated without any affect on viral replication in T-cell lines. PMID:8035478

  11. 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.

  12. 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

  13. 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

  14. 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

  15. Regulatory T cells and chronic immune activation in human immunodeficiency virus 1 (HIV-1)-infected children

    PubMed Central

    Freguja, R; Gianesin, K; Mosconi, I; Zanchetta, M; Carmona, F; Rampon, O; Giaquinto, C; De Rossi, A

    2011-01-01

    The function of CD4+ T cells with regulatory activity (Tregs) is the down-regulation of immune responses. This suppressive activity may limit the magnitude of effector responses, resulting in failure to control human immunodeficiency virus 1 (HIV-1) infection, but may also suppress chronic immune activation, a characteristic feature of HIV-1 disease. We evaluated the correlation between viral load, immune activation and Tregs in HIV-1-infected children. Eighty-nine HIV-1-infected children (aged 6–14 years) were included in the study and analysed for HIV-1 plasmaviraemia, HIV-1 DNA load, CD4 and CD8 cell subsets. Treg cells [CD4+ CD25highCD127lowforkhead box P3 (FoxP3high)] and CD8-activated T cells (CD8+CD38+) were determined by flow cytometry. Results showed that the number of activated CD8+CD38+ T cells increased in relation to HIV-1 RNA plasmaviraemia (r = 0·403, P < 0·0001). The proportion of Tregs also correlated positively with HIV-1 plasmaviraemia (r = 0·323, P = 0·002), but correlated inversely with CD4+ cells (r = −0·312, P = 0·004), thus suggesting a selective expansion along with increased viraemia and CD4+ depletion. Interestingly, a positive correlation was found between the levels of Tregs and CD8+CD38+ T cells (r = 0·305, P = 0·005), and the percentage of Tregs tended to correlate with HIV-1 DNA load (r = 0·224, P = 0·062). Overall, these findings suggest that immune activation contributes to the expansion of Treg cells. In turn, the suppressive activity of Tregs may impair effector responses against HIV-1, but appears to be ineffective in limiting immune activation. PMID:21438872

  16. Sequence-Specific Binding of Human Immunodeficiency Virus Type 1 Nucleocapsid Protein to Short Oligonucleotides

    PubMed Central

    Fisher, Robert J.; Rein, Alan; Fivash, Matthew; Urbaneja, Maria A.; Casas-Finet, José R.; Medaglia, Maxine; Henderson, Louis E.

    1998-01-01

    We have analyzed the binding of recombinant human immunodeficiency virus type 1 nucleocapsid protein (NC) to very short oligonucleotides by using surface plasmon resonance (SPR) technology. Our experiments, which were conducted at a moderate salt concentration (0.15 M NaCl), showed that NC binds more stably to runs of d(G) than to other DNA homopolymers. However, it exhibits far more stable binding with the alternating base sequence d(TG)n than with any homopolymeric oligodeoxyribonucleotide; thus, it shows a strong sequence preference under our experimental conditions. We found that the minimum length of an alternating d(TG) sequence required for stable binding was five nucleotides. Stable binding to the tetranucleotide d(TG)2 was observed only under conditions where two tetranucleotide molecules were held in close spatial proximity. The stable, sequence-specific binding to d(TG)n required that both zinc fingers be present, each in its proper position in the NC protein, and was quite salt resistant, indicating a large hydrophobic contribution to the binding. Limited tests with RNA oligonucleotides indicated that the preferential sequence-specific binding observed with DNA also occurs with RNA. Evidence was also obtained that NC can bind to nucleic acid molecules in at least two distinct modes. The biological significance of the specific binding we have detected is not known; it may reflect the specificity with which the parent Gag polyprotein packages genomic RNA or may relate to the functions of NC after cleavage of the polyprotein, including its role as a nucleic acid chaperone. PMID:9499042

  17. 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

  18. 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

  19. Specific and Independent Recognition of U3 and U5 att Sites by Human Immunodeficiency Virus Type 1 Integrase In Vivo

    PubMed Central

    Masuda, Takao; Kuroda, Marcelo J.; Harada, Shinji

    1998-01-01

    The retroviral attachment (att) sites at viral DNA ends are cis-acting regions essential for proviral integration. To investigate the sequence features of att important for human immunodeficiency virus type 1 (HIV-1) integration in vivo, we generated a series of 25 att mutants of HIV-1 by mutagenesis of the U3, U5, or both boundaries of att. Our results indicated that the terminal 11 or 12 bp of viral DNA are sufficient for specific recognition by HIV-1 integrase (IN) and suggested that IN might recognize each att site independently in vivo. PMID:9733892

  20. Real-Time PCR Quantification of Genital Shedding of Herpes Simplex Virus (HSV) and Human Immunodeficiency Virus (HIV) in Women Coinfected with HSV and HIV

    PubMed Central

    Legoff, Jérôme; Bouhlal, Hicham; Grésenguet, Gérard; Weiss, Helen; Khonde, Nzambi; Hocini, Hakim; Désiré, Nathalie; Si-Mohamed, Ali; de Dieu Longo, Jean; Chemin, Cécile; Frost, Eric; Pépin, Jacques; Malkin, Jean-Elie; Mayaud, Philippe; Bélec, Laurent

    2006-01-01

    The accuracy and usefulness of laboratory-developed real-time PCR procedures using a Light Cycler instrument (Roche Diagnostics) for detecting and quantifying human immunodeficiency virus type 1 (HIV-1) RNA and DNA as well as herpes simplex virus type 1 (HSV-1)/HSV-2 DNA in cervicovaginal secretions from women coinfected with HIV and HSV were evaluated. For HIV-1, the use of the NEC152 and NEC131 primer set and the NEC-LTR probe in the long terminal repeat gene allowed us to detect accurately the majority of HIV-1 subtypes of group M circulating in sub-Saharan Africa, including subtypes A, B, C, D, and G as well as circulating recombinant forms 02 and 11. The detection threshold of real-time PCR for HIV in cervicovaginal lavage samples was 5 copies per assay for both RNA and DNA; the intra- and interassay coefficients of variation of CT values were 1.30% and 0.69% (HIV-1 RNA) and 1.84% and 0.67% (HIV-1 DNA), respectively. Real-time PCR for HSV using primers and probe targeting the HSV DNA polymerase gene allowed both detection and quantification of HSV DNA and also differentiation between HSV-1 and HSV-2 genotypes. The detection threshold of real-time PCR for HSV was 5 copies per assay; the intra- and interassay coefficients of variation of CT values were 0.96% and 1.49%, respectively. Both manual and automated silica-based procedures were appropriate for combined extraction of HIV and HSV genomes from female genital secretions. Taken together, these findings indicate that real-time PCR may be used as a unique nucleic acid amplification procedure to detect and quantify HIV and HSV genomes in cervicovaginal secretions and thus to assess at reduced costs the genital shedding of both viruses in women included in intervention studies. PMID:16455895

  1. Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissue.

    PubMed Central

    Cohen, O J; Pantaleo, G; Holodniy, M; Schnittman, S; Niu, M; Graziosi, C; Pavlakis, G N; Lalezari, J; Bartlett, J A; Steigbigel, R T

    1995-01-01

    Although several immunologic and virologic markers measured in peripheral blood are useful for predicting accelerated progression of human immunodeficiency virus (HIV) disease, their validity for evaluating the response to antiretroviral therapy and their ability to accurately reflect changes in lymphoid organs remain unclear. In the present study, changes in certain virologic markers have been analyzed in peripheral blood and lymphoid tissue during antiretroviral therapy. Sixteen HIV-infected individuals who were receiving antiretroviral therapy with zidovudine for > or = 6 months were randomly assigned either to continue on zidovudine alone or to add didanosine for 8 weeks. Lymph node biopsies were performed at baseline and after 8 weeks. Viral burden (i.e., HIV DNA copies per 10(6) mononuclear cells) and virus replication in mononuclear cells isolated from peripheral blood and lymph node and plasma viremia were determined by semiquantitative polymerase chain reaction assays. Virologic and immunologic markers remained unchanged in peripheral blood and lymph node of patients who continued on zidovudine alone. In contrast, a decrease in virus replication in lymph nodes was observed in four of six patients who added didanosine to their regimen, and this was associated with a decrease in plasma viremia. These results indicate that decreases in plasma viremia detected during antiretroviral therapy reflect downregulation of virus replication in lymphoid tissue. Images Fig. 1 Fig. 2 Fig. 3 PMID:7597072

  2. Development of a Human Immunodeficiency Virus Vector-Based, Single-Cycle Assay for Evaluation of Anti-Integrase Compounds

    PubMed Central

    Bona, Roberta; Andreotti, Mauro; Buffa, Viviana; Leone, Pasqualina; Galluzzo, Clementina Maria; Amici, Roberta; Palmisano, Lucia; Mancini, Maria Grazia; Michelini, Zuleika; Di Santo, Roberto; Costi, Roberta; Roux, Alessandra; Pommier, Yves; Marchand, Christophe; Vella, Stefano; Cara, Andrea

    2006-01-01

    Therapeutic strategies aimed at inhibiting human immunodeficiency virus type 1 (HIV-1) replication employ a combination of drugs targeted to two viral enzymes (reverse transcriptase and protease) and to the viral entry/fusion step. However, the high propensity of HIV-1 to develop resistance makes the development of novel compounds targeting different steps of the HIV-1 life cycle essential. Among these, integrase (IN) inhibitors have successfully passed the early phases of clinical development. By preventing integration, IN inhibitors preclude viral replication while allowing production of extrachromosomal forms of viral DNA (E-DNA). Here, we describe an improved and standardized assay aimed at evaluating IN inhibitors by taking advantage of the transcriptional activity of E-DNA produced by HIV-derived vectors in the absence of replication-competent virus. In this context, the use of the firefly luciferase gene as a reporter gene provides a rapid and quantitative measure of viral-vector infectivity, thus making it a safe and cost-effective assay for evaluating novel IN inhibitors. PMID:17005823

  3. 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. PMID:26890489

  4. Small-Molecule Inhibition of Human Immunodeficiency Virus Type 1 Infection by Virus Capsid Destabilization▿

    PubMed Central

    Shi, Jiong; Zhou, Jing; Shah, Vaibhav B.; Aiken, Christopher; Whitby, Kevin

    2011-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection is dependent on the proper disassembly of the viral capsid, or “uncoating,” in target cells. The HIV-1 capsid consists of a conical multimeric complex of the viral capsid protein (CA) arranged in a hexagonal lattice. Mutations in CA that destabilize the viral capsid result in impaired infection owing to defects in reverse transcription in target cells. We describe here the mechanism of action of a small molecule HIV-1 inhibitor, PF-3450074 (PF74), which targets CA. PF74 acts at an early stage of HIV-1 infection and inhibits reverse transcription in target cells. We show that PF74 binds specifically to HIV-1 particles, and substitutions in CA that confer resistance to the compound prevent binding. A single point mutation in CA that stabilizes the HIV-1 core also conferred strong resistance to the virus without inhibiting compound binding. Treatment of HIV-1 particles or purified cores with PF74 destabilized the viral capsid in vitro. Furthermore, the compound induced the rapid dissolution of the HIV-1 capsid in target cells. PF74 antiviral activity was promoted by binding of the host protein cyclophilin A to the HIV-1 capsid, and PF74 and cyclosporine exhibited mutual antagonism. Our data suggest that PF74 triggers premature HIV-1 uncoating in target cells, thereby mimicking the activity of the retrovirus restriction factor TRIM5α. This study highlights uncoating as a step in the HIV-1 life cycle that is susceptible to small molecule intervention. PMID:20962083

  5. Small-molecule inhibition of human immunodeficiency virus type 1 infection by virus capsid destabilization.

    PubMed

    Shi, Jiong; Zhou, Jing; Shah, Vaibhav B; Aiken, Christopher; Whitby, Kevin

    2011-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection is dependent on the proper disassembly of the viral capsid, or "uncoating," in target cells. The HIV-1 capsid consists of a conical multimeric complex of the viral capsid protein (CA) arranged in a hexagonal lattice. Mutations in CA that destabilize the viral capsid result in impaired infection owing to defects in reverse transcription in target cells. We describe here the mechanism of action of a small molecule HIV-1 inhibitor, PF-3450074 (PF74), which targets CA. PF74 acts at an early stage of HIV-1 infection and inhibits reverse transcription in target cells. We show that PF74 binds specifically to HIV-1 particles, and substitutions in CA that confer resistance to the compound prevent binding. A single point mutation in CA that stabilizes the HIV-1 core also conferred strong resistance to the virus without inhibiting compound binding. Treatment of HIV-1 particles or purified cores with PF74 destabilized the viral capsid in vitro. Furthermore, the compound induced the rapid dissolution of the HIV-1 capsid in target cells. PF74 antiviral activity was promoted by binding of the host protein cyclophilin A to the HIV-1 capsid, and PF74 and cyclosporine exhibited mutual antagonism. Our data suggest that PF74 triggers premature HIV-1 uncoating in target cells, thereby mimicking the activity of the retrovirus restriction factor TRIM5α. This study highlights uncoating as a step in the HIV-1 life cycle that is susceptible to small molecule intervention. PMID:20962083

  6. 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

  7. Antiviral drugs other than zidovudine and immunomodulating therapies in human immunodeficiency virus infection. An overview.

    PubMed

    Clumeck, N; Hermans, P

    1988-08-29

    Although the management of patients with human immunodeficiency virus infections has focused on the treatment of opportunistic infections, or acquired immune deficiency syndrome (AIDS)-related cancers in end stages of the disease, therapies now aim at preventing the natural progression of the underlying disease. In addition to zidovudine many investigational drugs are proposed to treat AIDS-related complex patients. Most of these therapies can be divided into two major groups: (1) The first group includes agents with antiretroviral properties: nucleoside analogues, such as 2'-3'-dideoxycytidine and ribavirin, suramin, antimoniotungstate (heteropolyanion-23), foscarnet (phosphonoformate), interferons, peptide T, castanospermine, dextran sulfate, AL721, or ampligen. (2) The second group aims to restore the defective immune system; it includes thymosin (thymopentin), interleukin-2, cyclosporine, plasmapheresis, bone marrow transplantation, inosine, sodium diethyldithiocarbamate, methionine-enkephalin and carrisyn. At present, no drug other than zidovudine has proved as monotherapy to lengthen survival of human immunodeficiency virus-infected patients. PMID:2457313

  8. Human immunodeficiency virus type 1 infection despite prior immunization with a recombinant envelope vaccine regimen.

    PubMed Central

    McElrath, M J; Corey, L; Greenberg, P D; Matthews, T J; Montefiori, D C; Rowen, L; Hood, L; Mullins, J I

    1996-01-01

    With efforts underway to develop a preventive human immunodeficiency virus type 1 (HIV-1) vaccine, it remains unclear which immune responses are sufficient to protect against infection and whether prior HIV-1 immunity can alter the subsequent course of HIV-1 infection. We investigated these issues in the context of a volunteer who received six HIV-1LAI envelope immunizations and 10 weeks thereafter acquired HIV-1 infection through a high-risk sexual exposure. In contrast to nonvaccinated acutely infected individuals, anamnestic HIV-1-specific B- and T-cell responses appeared within 3 weeks in this individual, and neutralizing antibody preceded CD8+ cytotoxic responses. Despite an asymptomatic course and an initial low level of detectable infectious virus, a progressive CD4+ cell decline and dysfunction occurred within 2 years. Although vaccination elicited immunity to HIV-1 envelope, which was recalled upon HIV-1 exposure, it was insufficient to prevent infection and subsequent immunodeficiency. Images Fig. 2 PMID:8633000

  9. 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

  10. Minimal Requirement for a Lentivirus Vector Based on Human Immunodeficiency Virus Type 1

    PubMed Central

    Kim, V. Narry; Mitrophanous, Kyriacos; Kingsman, Susan M.; Kingsman, Alan J.

    1998-01-01

    The use of human immunodeficiency virus vectors for gene therapy is hampered by concern over their safety. This concern might be ameliorated, in part, if the viral accessory genes and proteins could be eliminated from the vector genomes and particles. Here we describe a minimal vector system that is capable of transducing nondividing cells and which does not contain tat, vif, vpr, vpu, and nef. PMID:9420292

  11. Minimal requirement for a lentivirus vector based on human immunodeficiency virus type 1.

    PubMed

    Kim, V N; Mitrophanous, K; Kingsman, S M; Kingsman, A J

    1998-01-01

    The use of human immunodeficiency virus vectors for gene therapy is hampered by concern over their safety. This concern might be ameliorated, in part, if the viral accessory genes and proteins could be eliminated from the vector genomes and particles. Here we describe a minimal vector system that is capable of transducing nondividing cells and which does not contain tat, vif, vpr, vpu, and nef. PMID:9420292

  12. Crusted Scabies: Presenting as erythroderma in a human immunodeficiency virus-seropositive patient

    PubMed Central

    Kulkarni, Shruti; Shah, Hiral; Patel, Bharti; Bhuptani, Neela

    2016-01-01

    Crusted scabies is a rare manifestation of scabies characterized by uncontrolled proliferation of mites in the skin. It is common in patients with sensory neuropathy, mentally retarded persons and in patients who are immunosuppressed. Further, crusted scabies can rarely present as erythroderma (<0.5% cases) necessitating a high index of suspicion for its diagnosis. Because of its rare occurrence, we are reporting a case of crusted scabies presenting as erythroderma, in a human immunodeficiency virus seropositive patient. PMID:27190417

  13. 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. PMID:27175350

  14. 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.

  15. Crusted Scabies: Presenting as erythroderma in a human immunodeficiency virus-seropositive patient.

    PubMed

    Kulkarni, Shruti; Shah, Hiral; Patel, Bharti; Bhuptani, Neela

    2016-01-01

    Crusted scabies is a rare manifestation of scabies characterized by uncontrolled proliferation of mites in the skin. It is common in patients with sensory neuropathy, mentally retarded persons and in patients who are immunosuppressed. Further, crusted scabies can rarely present as erythroderma (<0.5% cases) necessitating a high index of suspicion for its diagnosis. Because of its rare occurrence, we are reporting a case of crusted scabies presenting as erythroderma, in a human immunodeficiency virus seropositive patient. PMID:27190417

  16. Sweat gland carcinoma in a human immunodeficiency virus-infected patient.

    PubMed

    Toi, M; Kauffman, L; Peterson, L; Golitz, L; Myers, A

    1995-02-01

    Eccrine (sweat gland) carcinoma is a rare form of skin cancer that may be locally destructive. It is known to recur after resection and can metastasize to regional or distant lymph nodes. There have been two reported cases in association with patients immunocompromised as the result of organ transplantation (I. Penn: Prog Allergy. 37: 259, 1986). We report here the first case of sweat gland carcinoma in a patient infected with the human immunodeficiency virus. PMID:7539911

  17. Spectrum of false positivity for the fourth generation human immunodeficiency virus diagnostic tests.

    PubMed

    Liu, Peter; Jackson, Patrick; Shaw, Nathan; Heysell, Scott

    2016-01-01

    Novel fourth generation screening and confirmatory human immunodeficiency virus (HIV) assays are now commercially available and incorporated into new diagnostic algorithms. We report two cases involving a total of three patients which highlight the spectrum of false positivity for both the Abbott Architect p24 antigen/antibody assay and the confirmatory Multispot antibody differentiation test. We then discuss the mechanisms for false positivity and the associated clinical conditions or laboratory scenarios that may predispose to inaccurate interpretation. PMID:26734067

  18. Bifunctional Anti-Human Immunodeficiency Virus Type 1 Small Molecules with Two Novel Mechanisms of Action

    PubMed Central

    Huang, Li; Yuan, Xiong; Aiken, Christopher; Chen, Chin Ho

    2004-01-01

    A class of betulinic acid derivatives was synthesized to target two critical steps in the human immunodeficiency virus type 1 (HIV-1) replication cycle, entry and maturation. Each mechanism of HIV-1 inhibition is distinct from clinically available anti-HIV therapeutics. The viral determinants of the antientry and antimaturation activities are the bridging sheet of HIV-1 gp120 and the P24/p2 cleavage site, respectively. PMID:14742233

  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. 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

  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. 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

  3. The Naphthyridinone GSK364735 Is a Novel, Potent Human Immunodeficiency Virus Type 1 Integrase Inhibitor and Antiretroviral▿

    PubMed Central

    Garvey, Edward P.; Johns, Brian A.; Gartland, Margaret J.; Foster, Scott A.; Miller, Wayne H.; Ferris, Robert G.; Hazen, Richard J.; Underwood, Mark R.; Boros, Eric E.; Thompson, James B.; Weatherhead, Jason G.; Koble, Cecilia S.; Allen, Scott H.; Schaller, Lee T.; Sherrill, Ronald G.; Yoshinaga, Tomokazu; Kobayashi, Masanori; Wakasa-Morimoto, Chiaki; Miki, Shigeru; Nakahara, Koichiro; Noshi, Takeshi; Sato, Akihiko; Fujiwara, Tamio

    2008-01-01

    The naphthyridinone GSK364735 potently inhibited recombinant human immunodeficiency virus type 1 (HIV-1) integrase in a strand transfer assay (mean 50% inhibitory concentration ± standard deviation, 8 ± 2 nM). As expected based on the structure of the drug, it bound competitively with another two-metal binding inhibitor (Kd [binding constant], 6 ± 4 nM). In a number of different cellular assays, GSK364735 inhibited HIV replication with potency at nanomolar concentrations (e.g., in peripheral blood mononuclear cells and MT-4 cells, 50% effective concentrations were 1.2 ± 0.4 and 5 ± 1 nM, respectively), with selectivity indexes of antiviral activity versus in-assay cytotoxicity of at least 2,200. When human serum was added, the antiviral potency decreased (e.g., a 35-fold decrease in the presence of 100% human serum was calculated by extrapolation from the results of the MT-4 cell assay). In cellular assays, GSK364735 blocked viral DNA integration, with a concomitant increase in two-long-terminal-repeat circles. As expected, this integrase inhibitor was equally active against wild-type viruses and mutant viruses resistant to approved drugs targeting either reverse transcriptase or protease. In contrast, some but not all viruses resistant to other integrase inhibitors were resistant to GSK364735. When virus was passaged in the presence of the inhibitor, we identified resistance mutations within the integrase active site that were the same as or similar to mutations arising in response to other two-metal binding inhibitors. Finally, either additive or synergistic effects were observed when GSK364735 was tested in combination with approved antiretrovirals (i.e., no antagonistic effects were seen). Thus, based on all the data, GSK364735 exerted potent antiviral activity through the inhibition of viral DNA integration by interacting at the two-metal binding site within the catalytic center of HIV integrase. PMID:18160521

  4. Delayed Infection after Immunization with a Peptide from the Transmembrane Glycoprotein of the Feline Immunodeficiency Virus

    PubMed Central

    Richardson, J.; Moraillon, A.; Crespeau, F.; Baud, S.; Sonigo, P.; Pancino, G.

    1998-01-01

    Recent advances in the quantitative assessment of viral burden, by permitting the extension of criteria applied to assess the efficacy of vaccines from all-or-none protection to diminution of the viral burden, may allow the identification of original immunogens of value in combined vaccines. Peptides corresponding to three domains of the envelope glycoproteins of feline immunodeficiency virus that are recognized during natural infection were used to immunize cats. After challenge with a primary isolate of feline immunodeficiency virus, the development of acute infection was monitored by quantitative assessment of the viral burden in plasma and tissues by competitive reverse transcription-PCR, by measurement of the humoral response developed to viral components, and by lymphocyte subset analysis. Whereas immunization with two peptides derived from the surface glycoprotein had no effect on the early course of infection, immunization with a peptide derived from the transmembrane glycoprotein delayed infection, as reflected by a diminished viral burden in the early phase of primary infection and delayed seroconversion. This peptide, located in the membrane-proximal region of the extracellular domain, has homology to an epitope of human immunodeficiency virus type 1 recognized by a broadly neutralizing monoclonal antibody. These results suggest that lentivirus transmembrane glycoproteins share a determinant in the juxtamembrane ectodomain which could be of importance in the design of vaccines against AIDS. PMID:9499101

  5. [Antiviral activity of aqueous extracts of the birch fungus Inonotus obliquus on the human immunodeficiency virus].

    PubMed

    Shibnev, V A; Garaev, T M; Finogenova, M P; Kalnina, L B; Nosik, D N

    2015-01-01

    Fractions of aqueous and water-alcohol extracts of the birch fungus Inonotus obliquus have antiviral effect against the human immunodeficiency virus type 1 (HIV-1). Antiviral properties of low toxic extracts were manifested in the concentration of 5.0 μg/ml upon simultaneous application with the virus in the lymphoblastoid cells culture MT-4. The extract of the birch fungus can be used for development of new antiviral drugs, inhibitors of HIV-replication when used both in the form of individual drugs and as a part of complex therapy. PMID:26182655

  6. [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. PMID:27079412

  7. Efficient human immunodeficiency virus (HIV-1) infection of cells lacking PDZD8.

    PubMed

    Zhang, Shijian; Sodroski, Joseph

    2015-07-01

    PDZD8 can bind the capsid proteins of different retroviruses, and transient knockdown of PDZD8 results in a decrease in the efficiency of an early, post-entry event in the retrovirus life cycle. Here we used the CRISPR-CAS9 system to create cell lines in which PDZD8 expression is stably eliminated. The PDZD8-knockout cell lines were infected by human immunodeficiency virus (HIV-1) and murine leukemia virus as efficiently as the parental PDZD8-expressing cells. These results indicate that PDZD8 is not absolutely necessary for HIV-1 infection and diminishes its attractiveness as a potential target for intervention. PMID:25771112

  8. Recent advances in synthetic carbohydrate-based human immunodeficiency virus vaccines.

    PubMed

    Wang, Zhenyuan; Qin, Chunjun; Hu, Jing; Guo, Xiaoqiang; Yin, Jian

    2016-04-01

    An effective vaccine for human immunodeficiency virus (HIV) is urgently needed to prevent HIV infection and progression to acquired immune deficiency syndrome (AIDS). As glycosylation of viral proteins becomes better understood, carbohydrate-based antiviral vaccines against special viruses have attracted much attention. Significant efforts in carbohydrate synthesis and immunogenicity research have resulted in the development of multiple carbohydrate-based HIV vaccines. This review summarizes recent advances in synthetic carbohydrate-based vaccines design strategies and the applications of these vaccines in the prevention of HIV. PMID:26992403

  9. 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.

  10. A Pilot Study of Raltegravir Plus Combination Antiretroviral Therapy in Early Human Immunodeficiency Virus Infection: Challenges and Lessons Learned

    PubMed Central

    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

    Abstract 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. 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

  12. 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

  13. Characterization of a [open quotes]kissing[close quotes] hairpin complex derived from the human immunodeficiency virus genome

    SciTech Connect

    Chang, Kung-Yao; Tinoco, Ignacio Jr. )

    1994-08-30

    Base-pair formation between hairpin loops-a [open quotes]kissing[close quotes] complex-is an RNA-folding motif that links two elements of RNA secondary structure. It is also a unique protein recognition site involved in regulation of ColE1 plasmid DNA replication. The trans-activation response element (TAR), a hairpin and bulge at the 5[prime] end of the untranslated leader region of the human immunodeficiency virus 1 mRNA, enhances the transcription of the virus and is necessary for viral replication. Gel electrophoresis and absorbance melting curves indicate that a synthesized RNA hairpin (Tar*-16) with a loop sequence complementary to the TAR loop sequence (CUGGGA) associates specifically with a 16-nucleotide TAR hairpin (Tar-16) to form a stable complex. RNase T1 probing indicates that the three guanines in the Tar-16 loop become inaccessible in the complex. NMR imino proton spectra reveal that 5 base pairs are formed between the two hairpin loops (Tar-16 and Tar*-16); only the adenine at the 3[prime] terminus of the TAR loop does not form a base pair with the 5[prime]-terminal uracil of the complementary loop. A 14-nucleotide hairpin [CCUA-(UCCCAG)UAGG] with a loop sequence complementary to the TAR loop is conserved within the gag gene of human immunodeficiency virus 1. A synthesized RNA hairpin corresponding to this conserved sequence also binds to the Tar-16 hairpin with high affinity. It is possible that the same RNA loop-loop interaction occurs during the viral life cycle. 40 refs., 7 figs.

  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. PMID:17604205

  15. CD4-Independent Human Immunodeficiency Virus Infection Involves Participation of Endocytosis and Cathepsin B

    PubMed Central

    Yoshii, Hiroaki; Kamiyama, Haruka; Goto, Kensuke; Oishi, Kazunori; Katunuma, Nobuhiko; Tanaka, Yuetsu; Hayashi, Hideki; Matsuyama, Toshifumi; Sato, Hironori; Yamamoto, Naoki; Kubo, Yoshinao

    2011-01-01

    During a comparison of the infectivity of mNDK, a CD4-independent human immunodeficiency virus type 1 (HIV-1) strain, to various cell lines, we found that HeLa cells were much less susceptible than 293T and TE671 cells. Hybridoma cells between HeLa and 293T cells were as susceptible as 293T cells, suggesting that cellular factors enhance the mNDK infection in 293T cells. By screening a cDNA expression library in HeLa cells, cystatin C was isolated as an enhancer of the mNDK infection. Because cathepsin B protease, a natural ligand of cystatin C, was upregulated in HeLa cells, we speculated that the high levels of cathepsin B activities were inhibitory to the CD4-independent infection and that cystatin C enhanced the infection by impairing the excessive cathepsin B activity. Consistent with this idea, pretreatment of HeLa cells with 125 µM of CA-074Me, a cathepsin B inhibitor, resulted in an 8-fold enhancement of the mNDK infectivity. Because cathepsin B is activated by low pH in acidic endosomes, we further examined the potential roles of endosomes in the CD4-independent infection. Suppression of endosome acidification or endocytosis by inhibitors or by an Eps15 dominant negative mutant reduced the infectivity of mNDK in which CD4-dependent infections were not significantly impaired. Taken together, these results suggest that endocytosis, endosomal acidification, and cathepsin B activity are involved in the CD4-independent entry of HIV-1. PMID:21541353

  16. The structure of unliganded reverse transcriptase from the human immunodeficiency virus type 1.

    PubMed

    Rodgers, D W; Gamblin, S J; Harris, B A; Ray, S; Culp, J S; Hellmig, B; Woolf, D J; Debouck, C; Harrison, S C

    1995-02-14

    The crystal structure of the reverse transcriptase (RT) from the type 1 human immunodeficiency virus has been determined at 3.2-A resolution. Comparison with complexes between RT and the polymerase inhibitor Nevirapine [Kohlstaedt, L.A., Wang, J., Friedman, J.M., Rice, P.A. & Steitz, T.A. (1992) Science 256, 1783-1790] and between RT and an oligonucleotide [Jacobo-Molina, A., Ding, J., Nanni, R., Clark, A. D., Lu, X., Tantillo, C., Williams, R. L., Kamer, G., Ferris, A. L., Clark, P., Hizi, A., Hughes, S. H. & Arnold, E. (1993) Proc. Natl. Acad. Sci. USA 90, 6320-6324] reveals changes associated with ligand binding. The enzyme is a heterodimer (p66/p51), with domains labeled "fingers," "thumb," "palm," and "connection" in both subunits, and a ribonuclease H domain in the larger subunit only. The most striking difference between RT and both complex structures is the change in orientation of the p66 thumb (approximately 33 degrees rotation). Smaller shifts relative to the core of the molecule were also found in other domains, including the p66 fingers and palm, which contain the polymerase active site. Within the polymerase catalytic region itself, there are no rearrangements between RT and the RT/DNA complex. In RT/Nevirapine, the drug binds in the p66 palm near the polymerase active site, a region that is well-packed hydrophobic core in the unliganded enzyme. Room for the drug is provided by movement of a small beta-sheet within the palm domain of the Nevirapine complex. The rearrangement within the palm and thumb, as well as domain shifts relative to the enzyme core, may prevent correct placement of the oligonucleotide substrate when the drug is bound. PMID:7532306

  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. 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

  19. Normal T-cell turnover in sooty mangabeys harboring active simian immunodeficiency virus infection.

    PubMed

    Chakrabarti, L A; Lewin, S R; Zhang, L; Gettie, A; Luckay, A; Martin, L N; Skulsky, E; Ho, D D; Cheng-Mayer, C; Marx, P A

    2000-02-01

    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 alpha rearrangement (termed alpha1 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 alpha1 circle numbers in mangabeys as well as in macaques. Dilution of alpha1 circles by T-cell proliferation likely contributed to this decrease, since alpha1 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

  20. 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

  1. 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

  2. Anti-human immunodeficiency virus type 1 antibody complexes on platelets of seropositive thrombocytopenic homosexuals and narcotic addicts.

    PubMed Central

    Karpatkin, S; Nardi, M; Lennette, E T; Byrne, B; Poiesz, B

    1988-01-01

    Patients with human immunodeficiency virus type 1 (HIV-1) infection develop an immunologic thrombocytopenic purpura associated with markedly elevated platelet IgG, IgM, and C3C4 as well as serum immune complexes determined by the polyethylene glycol (PEG) method. Analysis of their serum PEG-precipitable immune complexes as well as platelet acid eluates revealed the presence of anti-HIV-1 antibody existing as a complex that eluted in the void volume of a Sephadex G-200 gel-filtration column. The complex binds to washed normal platelets, whereas affinity-purified anti-HIV-1 (gp120) antibody does not. HIV-1 antigen or proviral DNA was not detectable in the immune complexes or platelet extracts. However, anti-antibodies directed against anti-HIV-1 antibody were detectable in the immune complexes as well as platelet eluates. Approximately 50% of eluted platelet IgG contained anti-HIV-1 antibody. Thus the markedly elevated platelet immunoglobulin is partly due to the presence of anti-HIV-1 antibody complexes. This may be responsible for the enhanced platelet clearance and thrombocytopenia in patients with acquired immunodeficiency syndrome-related immunologic thrombocytopenia. Images PMID:3200854

  3. Herpes simplex virus type 1 colitis in a patient with common variable immunodeficiency syndrome.

    PubMed

    Dray, Xavier; Treton, Xavier; Mazeron, Marie-Christine; Lavergne-Slove, Anne; Joly, Francisca; Mimram, Dora; Attar, Alain; Tobelem, Gérard; Bouhnik, Yoram

    2006-05-01

    We report on a case of herpes simplex virus (HSV) type 1 colitis in a 69-year-old patient with common variable immunodeficiency syndrome. A treatment with polyvalent immunoglobulins was discontinued in April 2001. In March 2004 she developed chronic diarrhoea related to rectosigmoidal and caecal ulcerations. In November 2004, HSV was recovered in tissue culture from colonic biopsies. Valaciclovir was then started, leading the patient to clinical remission at day 4, and continued for a 6-week course (without any secondary antiviral prophylaxis). Colonic biopsies were negative for HSV by tissue culture and PCR within 3 weeks of antiviral treatment. Intravenous polyvalent immunoglobulin infusions were readministered within the third week of antiviral treatment. She has declared no clinical event since this period. Three months after the antiviral treatment was achieved, a rectosigmoidoscopy showed an ad-integrum macroscopic and histological mucosal healing whereas PCR was negative for HSV in the colonic tissue. As a large proportion of patients with common variable immunodeficiency syndrome present not only as a humoral immunodeficiency but also as a defect in the cellular immunity compartment (with T-cell deficits), HSV, as well as cytomegalovirus, should be investigated in patients with common variable immunodeficiency syndrome presenting colitis. PMID:16607152

  4. 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.

  5. 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.

  6. 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 (...

  7. 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

  8. The cytoplasmic domain of simian immunodeficiency virus transmembrane protein modulates infectivity.

    PubMed Central

    Chakrabarti, L; Emerman, M; Tiollais, P; Sonigo, P

    1989-01-01

    A striking characteristic of the simian immunodeficiency virus (SIV) and of the human immunodeficiency virus type 2 (HIV-2) is the presence of a nonsense mutation in the env gene resulting in the synthesis of a truncated transmembrane protein lacking the cytoplasmic domain. By mutagenesis of an infectious molecular clone of SIVmac142, we investigated the function of the cytoplasmic domain and the significance of the env nonsense mutation. When the nonsense codon (TAG) was replaced by a glutamine codon (CAG), the virus infected HUT78 cells with markedly delayed kinetics. This negative effect was counterselected in vitro as reversion of the slow phenotype frequently occurred. The sequencing of one revertant revealed the presence of a new stop codon three nucleotides 5' to the original mutation. Deletions or an additional nonsense mutation introduced 3' to the original stop codon did not modify SIV infectivity. In contrast, the same deletions or nonsense mutation introduced in the clone in which the stop codon was replaced by CAG abolished infectivity. These results indicated that the envelope domain located 3' to the stop codon is not necessary for in vitro replication. However, the presence of this domain in SIV transmembrane protein leads to a reduced infectivity. This negative effect might correspond to a function controlling the rate of spread of the virus during in vivo infection. Images PMID:2778881

  9. 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

  10. 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

  11. CD4-Negative Cells Bind Human Immunodeficiency Virus Type 1 and Efficiently Transfer Virus to T Cells

    PubMed Central

    Olinger, Gene G.; Saifuddin, Mohammed; Spear, Gregory T.

    2000-01-01

    The ability of human immunodeficiency virus strain MN (HIVMN), a T-cell line-adapted strain of HIV, and X4 and R5 primary isolates to bind to various cell types was investigated. In general, HIVMN bound to cells at higher levels than did the primary isolates. Virus bound to both CD4-positive (CD4+) and CD4-negative (CD4−) cells, including neutrophils, Raji cells, tonsil mononuclear cells, erythrocytes, platelets, and peripheral blood mononuclear cells (PBMC), although virus bound at significantly higher levels to PBMC. However, there was no difference in the amount of HIV that bound to CD4-enriched or CD4-depleted PBMC. Virus bound to CD4− cells was up to 17 times more infectious for T cells in cocultures than was the same amount of cell-free virus. Virus bound to nucleated cells was significantly more infectious than virus bound to erythrocytes or platelets. The enhanced infection of T cells by virus bound to CD4− cells was not due to stimulatory signals provided by CD4− cells or infection of CD4− cells. However, anti-CD18 antibody substantially reduced the enhanced virus replication in T cells, suggesting that virus that bound to the surface of CD4− cells is efficiently passed to CD4+ T cells during cell-cell adhesion. These studies show that HIV binds at relatively high levels to CD4− cells and, once bound, is highly infectious for T cells. This suggests that virus binding to the surface of CD4− cells is an important route for infection of T cells in vivo. PMID:10954556

  12. [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. PMID:14974895

  13. Biology of anemia, differential diagnosis, and treatment options in human immunodeficiency virus infection.

    PubMed

    Claster, Susan

    2002-05-15

    Anemia is the most common hematologic manifestation of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome. The causes of HIV-related anemia are multifactorial and include direct and indirect effects of HIV infection. HIV-related anemia generally is due to reduced red blood cell (RBC) production, secondary to a variety of causes, but it may also involve nutritional deficiencies, increased RBC destruction, or a combination of these problems. Evaluation of hemoglobin level, reticulocyte count, bilirubin, and mean corpuscular volume value and review of the peripheral blood smear are necessary for diagnosis. Treatment of HIV-related anemia should address the correctable underlying causes of this disorder, such as modifications of offending medications, nutritional deficiencies, and parvovirus infection. Patients with HIV infection have a blunted erythropoietin response to anemia. Therapeutic modalities for anemia that is not amenable to correction include blood transfusion and recombinant human erythropoietin (epoetin alfa). PMID:12001030

  14. 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

  15. Inhibition of apoptosis in human immunodeficiency virus-infected cells enhances virus production and facilitates persistent infection.

    PubMed Central

    Antoni, B A; Sabbatini, P; Rabson, A B; White, E

    1995-01-01

    Apoptosis is one of several mechanisms by which human immunodeficiency virus type 1 (HIV-1) exerts its cytopathic effects. CD4+ Jurkat T-cell lines overexpressing the adenovirus E1B 19K protein, a potent inhibitor of apoptosis, were used to examine the consequences of inhibition of apoptosis during acute and chronic HIV-1 infections. E1B 19K protein expression inhibited HIV-induced apoptosis, enhanced virus production, and established high levels of persistent viral infection. One E1B 19K-expressing line appeared to undergo HIV-induced death via a nonapoptotic mechanism, illustrating that HIV infection results in lymphocyte depletion through multiple pathways. Increased virus production associated with sustained cell viability suggests that therapeutic approaches involving inhibition of HIV-induced programmed cell death may be problematic. PMID:7884884

  16. Selective inactivation of human immunodeficiency virus with an ultrashort pulsed laser

    NASA Astrophysics Data System (ADS)

    Tsen, K. T.; Tsen, Shaw-Wei D.; Hung, Chien-Fu; Wu, T.-C.; Kibler, Karen; Jacobs, Bert; Kiang, Juliann G.

    2009-02-01

    Recently, femtosecond laser technology has been shown to be effective in the inactivation of non-pathogenic viruses. In this paper, we demonstrate for the first time that infectious numbers of pathogenic viruses such as Human Immunodeficiency Virus (HIV) can be reduced by irradiation with subpicosecond near infrared laser pulses at a moderate laser power density. By comparing the threshold laser power density for the inactivation of HIV with those of human red blood cells and mouse dendritic cells, we conclude that it is plausible to use the ultrashort pulsed laser to selectively inactivate blood-borne pathogens such as HIV while leaving the sensitive materials like human red blood cells unharmed. This finding has important implications in the development of a new laser technology for disinfection of viral pathogens in blood products and in the clinic.

  17. 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

  18. Nef Does Not Affect the Efficiency of Human Immunodeficiency Virus Type 1 Fusion with Target Cells

    PubMed Central

    Tobiume, Minoru; Lineberger, Janet E.; Lundquist, Christopher A.; Miller, Michael D.; Aiken, Christopher

    2003-01-01

    The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef stimulates viral infectivity by an unknown mechanism. Recent studies have suggested that Nef may act by regulating the efficiency of virus entry into cells. Here we provide evidence to the contrary. Using a quantitative assay of HIV-1 virus-cell fusion, we observed equivalent rates and extents of fusion of wild-type and Nef-defective HIV-1 particles with MT-4 cells and CD4-expressing HeLa cells. In studies using soluble CD4 (sCD4) to inhibit infection, wild-type and Nef-defective HIV-1 escaped the sCD4 block with similar kinetics. We conclude that Nef acts at a postentry step in infection, probably by facilitating intracellular transport of the HIV-1 ribonucleoprotein complex. PMID:12970449

  19. 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

  20. 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

  1. Efficacy and Safety of Tenofovir and Lamivudine in Combination with Efavirenz in Patients Co-infected with Human Immunodeficiency Virus and Hepatitis B Virus in China

    PubMed Central

    Wu, Ya-Song; Zhang, Wei-Wei; Ling, Xue-Mei; Yang, Lian; Huang, Shao-Biao; Wang, Xi-Cheng; Wu, Hao; Cai, Wei-Ping; Wang, Min; Wang, Hui; Liu, Yan-Fen; He, Hao-Lan; Wei, Fei-Li; Wu, Zun-You; Zhang, Fu-Jie

    2016-01-01

    Background: The prevalence of hepatitis B virus (HBV) infection is high among individuals infected with human immunodeficiency virus (HIV) in China. Both HIV and HBV can be treated with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC), so we evaluated the safety and efficacy of combination antiretroviral therapy (ART) that included TDF, 3TC, and efavirenz (EFV) among ART-naive individuals who were co-infected with HIV and HBV. Methods: One hundred HIV/HBV co-infected ARV-naive individuals were started on the regimen of TDF, 3TC, and EFV, and the levels of plasma HBV DNA, HIV RNA, and biochemical evaluation related to the function of liver and kidney were analyzed. Results: Concerning efficacy, this study found that by week 48, the vast majority co-infected participants receiving this ART regimen had undetectable HBV DNA levels (71%) and/or HIV RNA levels (90%). Concerning safety, this study found that the median estimated glomerular filtration rate of participants decreased from baseline (109 ml·min−1·1.73 m−2) to week 12 (104 ml·min−1·1.73 m−2) but was almost back to baseline at week 48 (111 ml·min−1·1.73 m−2). Conclusion: This combination ART regimen is safe and effective for patients with HIV/HBV co-infection. Trial Registration: ClinicalTrials.gov, NCT01751555; https://clinicaltrials.gov/ct2/show/NCT01751555. PMID:26831232

  2. Epstein-Barr virus-positive and -negative B-cell lines can be infected with human immunodeficiency virus types 1 and 2.

    PubMed Central

    Monroe, J E; Calender, A; Mulder, C

    1988-01-01

    Human immunodeficiency virus type 1 (HIV-1) can infect CD4+ lymphocytes, monocytes-macrophages, and various other cell lines, including B-cell lines. To study the parameters of B-cell infections, we examined the susceptibility of 24 B-lymphoid cell lines to both HIV-1 and HIV-2 infections. These cell lines included a series of Epstein-Barr virus (EBV) genome-negative Burkitt's lymphoma cell lines and their EBV-converted counterparts. To infect these cells we used two HIV-1 isolates and one HIV-2 isolate. Infections were monitored with a cytoplasmic RNA dot-blot and a syncytium assay. HIV infection was also studied by a novel method based on electrophoresis of DNA liberated from cells that were lysed in situ in the well of an agarose gel. All human B-cell lines could be infected with HIV-1, regardless of the presence of EBV genomes; thus, EBV infection had no major effect on HIV susceptibility of B-cell lines. Integrated proviral HIV genomes could be detected by Southern blot analysis of DNA extracted from long-term, non-HIV-producing B-cell lines. This study suggests that B-lymphoid cells may serve as reservoirs for latent or persistent HIV infections in vivo, even in the absence of EBV infection. Images PMID:2841499

  3. 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...

  4. 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

  5. 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 ...

  6. 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…

  7. 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…

  8. 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

  9. Generation and Characterization of Neutralizing Human Monoclonal Antibodies against Human Immunodeficiency Virus Type 1 Tat Antigen

    PubMed Central

    Moreau, Emmanuel; Hoebeke, Johan; Zagury, Daniel; Muller, Sylviane; Desgranges, Claude

    2004-01-01

    The human immunodeficiency virus Tat regulatory protein is essential for virus replication and pathogenesis. From human peripheral blood mononuclear cells of three Tat toxoid-immunized volunteers, we isolated five Tat-specific human monoclonal antibodies (HMAbs): two full-length immunoglobulin G (IgG) antibodies and three single-chain fragment-variable (scFv) antibodies. The two IgGs were mapped to distinct epitopes within the basic region of Tat, and the three scFvs were mapped to the N-terminal domain of Tat. The three scFvs were highly reactive with recombinant Tat in Western blotting or immunoprecipitation, but results were in contrast to those for the two IgGs, which are sensitive to a particular folding of the protein. In transactivation assays, scFvs were able to inhibit both active recombinant Tat and native Tat secreted by a transfected CEM cell line while IgGs neutralized only native Tat. These HMAbs were able to reduce viral p24 production in human immunodeficiency virus type 1 strain IIIB chronically infected cell lines in a dose-dependent manner. PMID:15016898

  10. Analysis of human immunodeficiency virus type 1 nef gene sequences present in vivo.

    PubMed Central

    Shugars, D C; Smith, M S; Glueck, D H; Nantermet, P V; Seillier-Moiseiwitsch, F; Swanstrom, R

    1993-01-01

    The nef genes of the human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2) and the related simian immunodeficiency viruses (SIVs) encode a protein (Nef) whose role in virus replication and cytopathicity remains uncertain. As an attempt to elucidate the function of nef, we characterized the nucleotide and corresponding protein sequences of naturally occurring nef genes obtained from several HIV-1-infected individuals. A consensus Nef sequence was derived and used to identify several features that were highly conserved among the Nef sequences. These features included a nearly invariant myristylation signal, regions of sequence polymorphism and variable duplication, a region with an acidic charge, a (Pxx)4 repeat sequence, and a potential protein kinase C phosphorylation site. Clustering of premature stop codons at position 124 was noted in 6 of the 54 Nef sequences. Further analysis revealed four stretches of residues that were highly conserved not only among the patient-derived HIV-1 Nef sequences, but also among the Nef sequences of HIV-2 and the SIVs, suggesting that Nef proteins expressed by these retroviruses are functionally equivalent. The "Nef-defining" sequences were used to evaluate the sequence alignments of known proteins reported to share sequence similarity with Nef sequences and to conduct additional computer-based searches for similar protein sequences. A gene encoding the consensus Nef sequence was also generated. This gene encodes a full-length Nef protein that should be a valuable tool in further studies of Nef function. Images PMID:8043040

  11. Antiviral properties of palinavir, a potent inhibitor of the human immunodeficiency virus type 1 protease.

    PubMed Central

    Lamarre, D; Croteau, G; Wardrop, E; Bourgon, L; Thibeault, D; Clouette, C; Vaillancourt, M; Cohen, E; Pargellis, C; Yoakim, C; Anderson, P C

    1997-01-01

    Palinavir is a potent inhibitor of the human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) proteases. Replication of laboratory strains (HIV-1, HIV-2, and simian immunodeficiency virus) and HIV-1 clinical isolates is inhibited by palinavir with 50% effective concentrations ranging from 0.5 to 30 nM. The average cytotoxic concentration of palinavir (35 microM) in the various target cells indicates a favorable therapeutic index. Potent antiviral activity is retained with increased doses of virus and with clinical isolates resistant to zidovudine (AZT), didanosine (ddI), or nevirapine. Combinations of palinavir with either AZT, ddI, or nevirapine demonstrate synergy or additivity in the inhibition of HIV-1 replication. Palinavir retains anti-HIV-1 activity when administered postinfection until times subsequent to the reverse transcription step. In chronically infected CR-10 cells, palinavir blocks Gag precursor polyprotein processing completely, reducing greater than 99% of infectious particle production. The results indicate that the antiviral activity of palinavir is specific to inhibition of the viral protease and occurs at a late stage in the replicative cycle of HIV-1. On the basis of the potent in vitro activity, low-level cytotoxicity, and other data, palinavir was selected for in-depth preclinical evaluation. PMID:9145853

  12. Development of second- and third-generation bovine immunodeficiency virus-based gene transfer systems.

    PubMed

    Matukonis, Meghan; Li, Mengtao; Molina, Rene P; Paszkiet, Brian; Kaleko, Michael; Luo, Tianci

    2002-07-20

    Lentivirus-based gene transfer systems have demonstrated their utility in mediating gene transfer to dividing and nondividing cells both in vitro and in vivo. An early-generation gene transfer system developed from bovine immunodeficiency virus (BIV) has been described (Berkowitz et al., J. Virol. 2001;75:3371-3382). In this paper, we describe the development of second-generation (three-plasmid) and third-generation (four-plasmid) BIV-based systems. All accessory genes (vif, vpw, vpy, and tmx) and the regulatory gene tat were deleted or largely truncated from the packaging construct. Furthermore, we split the packaging function into two constructs by expressing Rev in a separate plasmid. Together with our minimal BIV transfer vector construct and a vesicular stomatitis virus G glycoprotein-expressing plasmid, the BIV vectors were generated. The vectors produced by the three- and four-plasmid systems had titers greater than 1 x 10(6) transducing units per milliliter and were fully functional as indicated by their ability to efficiently transduce both dividing and nondividing cells. These results suggest that the accessory genes vif, vpw, vpy, and tmx are dispensable for functional BIV vector development. The modifications made to the packaging constructs improve the safety profile of the vector system. Finally, BIV vectors provide an alternative to human immunodeficiency virus-based gene transfer systems. PMID:12162812

  13. Human Immunodeficiency Virus Diagnostic Testing: 30 Years of Evolution.

    PubMed

    Alexander, Thomas S

    2016-04-01

    A concern during the early AIDS epidemic was the lack of a test to identify individuals who carried the virus. The first HIV antibody test, developed in 1985, was designed to screen blood products, not to diagnose AIDS. The first-generation assays detected IgG antibody and became positive 6 to 12 weeks postinfection. False-positive results occurred; thus, a two-test algorithm was developed using a Western blot or immunofluorescence test as a confirmatory procedure. The second-generation HIV test added recombinant antigens, and the third-generation HIV tests included IgM detection, reducing the test-negative window to approximately 3 weeks postinfection. Fourth- and fifth-generation HIV assays added p24 antigen detection to the screening assay, reducing the test-negative window to 11 to 14 days. A new algorithm addressed the fourth-generation assay's ability to detect both antibody and antigen and yet not differentiate between them. The fifth-generation HIV assay provides separate antigen and antibody results and will require yet another algorithm. HIV infection may now be detected approximately 2 weeks postexposure, with a reduced number of false-positive results. PMID:26936099

  14. 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

  15. Ocelots on Barro Colorado Island are infected with feline immunodeficiency virus but not other common feline and canine viruses.

    PubMed

    Franklin, Samuel P; Kays, Roland W; Moreno, Ricardo; TerWee, Julie A; Troyer, Jennifer L; VandeWoude, Sue

    2008-07-01

    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

  16. Influence of immune activation and inflammatory response on cardiovascular risk associated with the human immunodeficiency virus

    PubMed Central

    Beltrán, Luis M; Rubio-Navarro, Alfonso; Amaro-Villalobos, Juan Manuel; Egido, Jesús; García-Puig, Juan; Moreno, Juan Antonio

    2015-01-01

    Patients infected with the human immunodeficiency virus (HIV) have an increased cardiovascular risk. Although initially this increased risk was attributed to metabolic alterations associated with antiretroviral treatment, in recent years, the attention has been focused on the HIV disease itself. Inflammation, immune system activation, and endothelial dysfunction facilitated by HIV infection have been identified as key factors in the development and progression of atherosclerosis. In this review, we describe the epidemiology and pathogenesis of cardiovascular disease in patients with HIV infection and summarize the latest knowledge on the relationship between traditional and novel inflammatory, immune activation, and endothelial dysfunction biomarkers on the cardiovascular risk associated with HIV infection. PMID:25609975

  17. 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

  18. 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

  19. Bilateral Peripheral Facial Palsy in a Patient with Human Immunodeficiency Virus (HIV) Infection

    PubMed Central

    Kim, Min Su; Yoon, Hee Jung; Kim, Hai Jin; Nam, Ji Sun; Choi, Sung Ho; Kim, June Myung

    2006-01-01

    Neurological complications are important causes of morbidity and mortality in patients with human immunodeficiency virus (HIV) infection. They can occur at any stage of the disease and can affect any level of the central or peripheral nervous systems. In the literature, several cases of HIV-associated facial paralysis have been reported; however, bilateral facial palsy is rarely reported. In this paper, we present the first case in Korea, of a bilateral facial palsy occurring as the first clinical manifestation of HIV infection. PMID:17066521

  20. FAST TRACK COMMUNICATION: Selective inactivation of human immunodeficiency virus with subpicosecond near-infrared laser pulses

    NASA Astrophysics Data System (ADS)

    Tsen, K. T.; Tsen, Shaw-Wei D.; Hung, Chien-Fu; Wu, T.-C.; Kiang, Juliann G.

    2008-06-01

    We demonstrate for the first time that human immunodeficiency virus (HIV) can be inactivated by irradiation with subpicosecond near-infrared laser pulses at a moderate laser power density. By comparing the threshold laser power density for the inactivation of HIV with those of human red blood cells and mouse dendritic cells, we conclude that it is plausible to use the ultrashort pulsed laser to selectively inactivate blood-borne pathogens such as HIV while leaving sensitive materials like human red blood cells unharmed. This finding has important implications in the development of a new laser technology for disinfection of viral pathogens in blood products and in the clinic.

  1. Human immunodeficiency virus infection and diffuse polyneuropathy. Implications for rehabilitation medicine.

    PubMed Central

    Mukand, J. A.

    1991-01-01

    Patients at various stages of human immunodeficiency virus (HIV) infection require rehabilitation services. These patients present problems for each of the disciplines in a rehabilitation team, and all team members must confront the psychosocial and ethical issues involved with the disease. Patients with HIV infection may have polyneuropathy with multisystem involvement, including dysphagia, autonomic dysfunction, respiratory failure, bowel and bladder dysfunction, generalized weakness, a painful sensory neuropathy, and depression. Guidelines are presented for determining if inpatient rehabilitation or other settings are appropriate. Case management is a valuable strategy for the rehabilitation of patients with this complicated disorder. PMID:1866948

  2. [Non-dermatophytic moulds: onychomycosis in four patients infected with the human immunodeficiency virus].

    PubMed

    de Magalhães Lima, Kedma; Machado Barbosa de Castro, Célia Maria; Fonsêca Nogueira Cambuim, Idalina Inês; Carvalhaes de Oliveira, Jeferson; Delgado, Marília; Sette de Melo Rego, Rossana

    2008-03-01

    Patients infected with human immunodeficiency virus (HIV) are a risk group for onychomycosis, fungal infections caused mainly by dermatophytes and yeast. However, non-dermatohytic moulds are becoming common agents for nail infections in this population of patients. We report four cases of onychomycosis caused by non-dermatophytic moulds (Aspergillus niger, Scytalidium hyalinum, Scytalidium dimidiatum and Fusarium solani) in patients infected with HIV from Recife, Pernambuco, Brazil. Onychomicosis by non-dermatophytic species in HIV-positive patients requires special attention in the clinical and the laboratory. A proper diagnosis is necessary to establish the specific and adequate treatment, preventing fungal invasion. PMID:18338928

  3. Visceral leishmaniasis with cutaneous lesions in a patient infected with human immunodeficiency virus.

    PubMed

    Ara, M; Maillo, C; Peón, G; Clavel, A; Cuesta, J; Grasa, M P; Carapeto, F J

    1998-07-01

    We report a case of visceral leishmaniasis (VL) with cutaneous lesions in a patient infected with human immunodeficiency virus (HIV). The cutaneous lesions consisted of erythematous papules on the legs. Biopsy of one lesion showed abundant Leishmania amastigotes within epithelial cells of an eccrine sweat gland in the dermis. Leishmania organisms were also found in a blood smear. Rapid and complete clearance of the cutaneous lesions was achieved after antimony therapy. Cutaneous lesions in VL are being reported increasingly frequently in patients with HIV infection and their significance remains in discussion. PMID:9764161

  4. Human immunodeficiency virus among people who inject drugs: is risk increasing in Europe?

    PubMed

    Hedrich, D; Kalamara, E; Sfetcu, O; Pharris, A; Noor, A; Wiessing, L; Hope, V; Van de Laar, M

    2013-01-01

    In most European Union (EU)/European Economic Area (EEA) countries, between 2010 and 2012, reports of new human immunodeficiency virus (HIV) diagnoses among people who inject drugs have been stable or declining. HIV outbreaks in Greece and Romania, first reported in 2011, continue and economic conditions hinder provision of effective response coverage. When measured against some established thresholds, prevention coverage remains inadequate in at least one-third of EU/EEA countries. Urgent consideration to scale up prevention efforts is merited. PMID:24308980

  5. 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

  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. PMID:26933317

  7. 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

  8. 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

  9. 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

  10. 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

  11. Toxic epidermal necrolysis caused by fluconazole in a patient with human immunodeficiency virus infection.

    PubMed

    George, Jacob; Sharma, Arun; Dixit, Ramakant; Chhabra, Naveen; Sharma, Smita

    2012-07-01

    Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) are rare but serious dermatologic disorders. These grave conditions present as medical emergency, requiring prompt diagnosis and management. These are often drug induced and various groups of drugs, such as sulfa drugs, NSAIDS, etc., have been implicated as to cause TEN. Fluconazole is a commonly used drug with mild side effects. TEN caused by fluconazole is rare, and till now only few cases have been reported in the literature. We present a case of TEN in a human immunodeficiency virus infected man following fluconazole therapy in view of its rare occurrence. PMID:23129968

  12. 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

  13. De Novo Belatacept in a Human Immunodeficiency Virus-Positive Kidney Transplant Recipient.

    PubMed

    Cohen, E A; Mulligan, D; Kulkarni, S; Tichy, E M

    2016-09-01

    Benefits of belatacept-based immunosuppressive regimens in human immunodeficiency virus (HIV)-positive renal transplant recipients include avoidance of drug interactions between calcineurin inhibitors and highly active antiretroviral agents and decreased likelihood or severity of nonimmune toxicities such as new-onset diabetes after transplant, hyperlipidemia and hypertension. We report a successful case of de novo belatacept at >18 mo from transplant in an HIV-positive black man aged 50 years who received his first transplant from a living related kidney donor. To our knowledge, this case is the first reported of belatacept use in an HIV-positive renal transplant recipient. PMID:27137752

  14. Protein structure-based design of potent orally bioavailable, nonpeptide inhibitors of human immunodeficiency virus protease.

    PubMed Central

    Reich, S H; Melnick, M; Davies, J F; Appelt, K; Lewis, K K; Fuhry, M A; Pino, M; Trippe, A J; Nguyen, D; Dawson, H

    1995-01-01

    A class of potent nonpeptidic inhibitors of human immunodeficiency virus protease has been designed by using the three-dimensional structure of the enzyme as a guide. By employing iterative protein cocrystal structure analysis, design, and synthesis the binding affinity of the lead compound was incrementally improved by over four orders of magnitude. An inversion in inhibitor binding mode was observed crystallographically, providing information critical for subsequent design and highlighting the utility of structural feedback in inhibitor optimization. These inhibitors are selective for the viral protease enzyme, possess good antiviral activity, and are orally available in three species. Images Fig. 2 PMID:7724556

  15. 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.

  16. Domestic cats infected with lion or puma lentivirus develop anti-feline immunodeficiency virus immune responses.

    PubMed

    VandeWoude, Sue; Hageman, Catherine L; Hoover, Edward A

    2003-09-01

    Attenuated live viral strains have afforded significant protection against virus challenge in HIV vaccine models. Although both cellular and humoral immunity are assumed to be vital for protection, specific parameters consistently associated with control of infection have been elusive. Our previous studies have shown that lentiviruses from 2 nondomestic feline species--lion (Pathera leo) and puma (Felis concolor)--persistently but nonpathogenetically infect domestic cats (Felis domestica). Moreover, infection with either the puma lentivirus (PLV) or lion lentivirus (LLV) conferred partial protection against superinfection with virulent feline immunodeficiency virus (FIV), the feline equivalent of HIV. To determine whether domestic cats infected by the lentiviruses of pumas or lions generate cross-reactive immune responses, we infected groups of 5 domestic cats with PLV, LLV, or a sham control and then monitored virus load, hematologic parameters, antibody protection, proliferative responses, and the ability of blood mononuclear cells to inhibit LLV, PLV, and FIV replication in vitro. All cats inoculated with LLV or PLV developed persistent infection, and low-level cell-associated viremia has been previously described. Infected cats also generated robust antibody titers and lymphocytes that proliferated in response to viral antigens and downregulated PLV, LLV, and FIV replication in vitro. This latter activity was CD8 cell associated for PLV and LLV inhibition but not for FIV inhibition. Thus, cats infected with the phylogenetically more ancient and less pathogenic feline lentiviruses generated humoral and cell-mediated immune responses reactive against both the homologous viruses and the heterologous FIV of domestic cats, which correlated with decreased viral load. These results are analogous to protection studies with attenuated primate immunodeficiency viruses and provide a system by which to examine adaptation, interference, and cross protection among

  17. 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

  18. Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy

    PubMed Central

    Matusali, G.; Dereuddre-Bosquet, N.; Le Tortorec, A.; Moreau, M.; Satie, A.-P.; Mahé, D.; Roumaud, P.; Bourry, O.; Sylla, N.; Bernard-Stoecklin, S.; Pruvost, A.; Le Grand, R.

    2015-01-01

    ABSTRACT A number of men receiving prolonged suppressive highly active antiretroviral therapy (HAART) still shed human immunodeficiency virus (HIV) in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with simian immunodeficiency virus mac251 (SIVmac251) who were treated for 4 months with HAART, which was intensified over the last 7 weeks with an integrase inhibitor. We showed that a subset of treated animals continued shedding SIV in semen despite efficient HAART. This shedding was not associated with low antiretroviral drug concentrations in semen or in testis, epididymis, seminal vesicles, and prostate. HAART had no significant impact on SIV RNA in the urethra, whereas it drastically reduced SIV RNA levels in the prostate and vas deferens and to a lesser extent in the epididymis and seminal vesicle. The only detectable SIV RNA-positive cells within the male genital tract after HAART were urethral macrophages. SIV DNA levels in genital tissues were not decreased by HAART, suggesting the presence throughout the male genital tract of nonproductively infected cells. In conclusion, our results demonstrate that 4 months of HAART induced variable and limited control of viral infection in the male reproductive organs, particularly in the urethra, and suggest that infected long-lived cells in the male genital tract may be involved in persistent seminal shedding during HAART. These results pave the way for further investigations of male genital organ infection in long-term-treated infected individuals. IMPORTANCE A substantial subset of men receiving prolonged HAART suppressing viral loads in the blood still harbor HIV in semen, and cases of sexual transmission have been reported. To understand the origin of this persistence, we analyzed the semen and male reproductive tissues from SIV

  19. DNA Tumor Viruses and Cell Metabolism

    PubMed Central

    Mushtaq, Muhammad; Darekar, Suhas

    2016-01-01

    Viruses play an important role in cancerogenesis. It is estimated that approximately 20% of all cancers are linked to infectious agents. The viral genes modulate the physiological machinery of infected cells that lead to cell transformation and development of cancer. One of the important adoptive responses by the cancer cells is their metabolic change to cope up with continuous requirement of cell survival and proliferation. In this review we will focus on how DNA viruses alter the glucose metabolism of transformed cells. Tumor DNA viruses enhance “aerobic” glycolysis upon virus-induced cell transformation, supporting rapid cell proliferation and showing the Warburg effect. Moreover, viral proteins enhance glucose uptake and controls tumor microenvironment, promoting metastasizing of the tumor cells. PMID:27034740

  20. The requirement for nucleoporin NUP153 during human immunodeficiency virus type 1 infection is determined by the viral capsid.

    PubMed

    Matreyek, Kenneth A; Engelman, Alan

    2011-08-01

    Lentiviruses likely infect nondividing cells by commandeering host nuclear transport factors to facilitate the passage of their preintegration complexes (PICs) through nuclear pore complexes (NPCs) within nuclear envelopes. Genome-wide small interfering RNA screens previously identified karyopherin β transportin-3 (TNPO3) and NPC component nucleoporin 153 (NUP153) as being important for infection by human immunodeficiency virus type 1 (HIV-1). The knockdown of either protein significantly inhibited HIV-1 infectivity, while infection by the gammaretrovirus Moloney murine leukemia virus (MLV) was unaffected. Here, we establish that primate lentiviruses are particularly sensitive to NUP153 knockdown and investigate HIV-1-encoded elements that contribute to this dependency. Mutants lacking functional Vpr or the central DNA flap remained sensitive to NUP153 depletion, while MLV/HIV-1 chimera viruses carrying MLV matrix, capsid, or integrase became less sensitive when the latter two elements were substituted. Two capsid missense mutant viruses, N74D and P90A, were largely insensitive to NUP153 depletion, as was wild-type HIV-1 when cyclophilin A was depleted simultaneously or when infection was conducted in the presence of cyclosporine A. The codepletion of NUP153 and TNPO3 yielded synergistic effects that outweighed those calculated based on individual knockdowns, indicating potential interdependent roles for these factors during HIV-1 infection. Quantitative PCR revealed normal levels of late reverse transcripts, a moderate reduction of 2-long terminal repeat (2-LTR) circles, and a relatively large reduction in integrated proviruses upon NUP153 knockdown. These results suggest that capsid, likely by the qualities of its uncoating, determines whether HIV-1 requires cellular NUP153 for PIC nuclear import. PMID:21593146

  1. Infection frequency of dendritic cells and CD4+ T lymphocytes in spleens of human immunodeficiency virus-positive patients.

    PubMed Central

    McIlroy, D; Autran, B; Cheynier, R; Wain-Hobson, S; Clauvel, J P; Oksenhendler, E; Debré, P; Hosmalin, A

    1995-01-01

    Dendritic cells (DC) are specialized antigen-presenting leukocytes that are responsible for the activation of naive as well as memory T lymphocytes. If infected by human immunodeficiency virus (HIV), DC may transfer virus to CD4+ lymphocytes. However, the question of whether DC are infected in vivo is controversial. As HIV infection is more active in secondary lymphoid organs than in blood, infection of splenic DC isolated from HIV-seropositive patients was investigated. Splenic DC were first enriched and characterized by flow cytometry from HIV- donors. After direct isolation, they were negative for monocyte and T- and B-lymphocyte markers, negative for CD1a, but positive for major histocompatibility complex class II and CD4. After in vitro maturation, major histocompatibility complex class II expression increased, while CD4 expression was lost. Extensive purification from the spleens of seven HIV+ patients was performed by fluorescence-activated cell sorting. The frequency of cells harboring HIV DNA in purified populations was quantified by limiting-dilution PCR. Directly isolated DC (average, 1/3,000; range, 1/720 to 1/18,000) were in each patient 10 to 100 times less infected than CD4+ T lymphocytes (average, 1/52; range, 1/17 to 1/190). On average, 1/1,450 (1/320 to 1/6,100) unseparated mononuclear splenocytes (containing 5% CD4+ lymphocytes) harbored HIV DNA. In conclusion, in these HIV+ patient spleens, DC seem to be infected, but HIV-DNA positive CD4+ T lymphocytes accounted for the vast majority of infected mononuclear splenocytes. PMID:7609039

  2. Formation of a Human Immunodeficiency Virus Type 1 Core of Optimal Stability Is Crucial for Viral Replication

    PubMed Central

    Forshey, Brett M.; von Schwedler, Uta; Sundquist, Wesley I.; Aiken, Christopher

    2002-01-01

    Virions of human immunodeficiency virus type 1 (HIV-1) and other lentiviruses contain conical cores consisting of a protein shell composed of the viral capsid protein (CA) surrounding an internal viral ribonucleoprotein complex. Although genetic studies have implicated CA in both early and late stages of the virus replication cycle, the mechanism of core disassembly following penetration of target cells remains undefined. Using quantitative assays for analyzing HIV-1 core stability in vitro, we identified point mutations in CA that either reduce or increase the stability of the HIV-1 core without impairing conical core formation in virions. Alterations in core stability resulted in severely attenuated HIV-1 replication and impaired reverse transcription in target cells with only minimal effects on viral DNA synthesis in permeabilized virions in vitro. We conclude that formation of a viral core of optimal stability is a prerequisite for efficient HIV-1 infection and suggest that disassembly of the HIV-1 core is a regulated step in infection that may be an attractive target for pharmacologic intervention. PMID:11991995

  3. 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

    Chang, Joy; Tarasova, Tetyana; Shanmugam, Vedapuri; Azarskova, Marianna; Nguyen, Shon; Hurlston, Mackenzie; Sabatier, Jennifer; Zhang, Guoqing; Osmanov, Saladin; Ellenberger, Dennis; Yang, Chunfu; Vitek, Charles; Liulchuk, Maria; Nizova, Natalya

    2015-12-01

    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

  4. 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

  5. Comparison of different methods for detecting human immune deficiency virus in human immunodeficiency virus-seropositive hemophiliacs.

    PubMed

    Schneweis, K E; Ackermann, A; Friedrich, A; Kleim, J P; Kornau, K; Ruff, R; Siefer-Wippermann, B

    1989-10-01

    Since the detection of antibodies against the human immune deficiency virus (HIV) does not definitely prove HIV infection in hemophiliacs, virus detection was attempted by virus isolation from the peripheral blood monocytes (PBL), by demonstration of p24 antigen and decline of p24 antibody, and by detection of viral DNA by the polymerase chain reaction (PCR). Virus isolation was optimized by immediate coculture of PBL and by replacement of the reverse transcriptase test by the p24 antigen test, whereas the elimination of CD8+ lymphocytes proved to be unnecessary. Virus detection was dependent on the clinical stage of the illness. Virus isolation in 70 of 211 patients (33%) was more sensitive than detection of p24 antigen or decline of p24 antibody. PCR was performed in 25 patients and indicated infection in all of 15 isolation-positive cases and in 6 of 10 patients from whom virus was not isolated. Changes from negative to positive virus culture and from a weakly fusiogenic to a highly fusiogenic isolate were often accompanied by a progression of the disease. The results suggest that reactivation of HIV occurs when immune deficiency has become manifest. Apparently virus isolation detects only the virus already reactivated in vivo, whereas the PCR may also detect latent virus. PMID:2689596

  6. 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

  7. Alternating versus continuous drug regimens in combination chemotherapy of human immunodeficiency virus type 1 infection in vitro.

    PubMed Central

    Mazzulli, T; Rusconi, S; Merrill, D P; D'Aquila, R T; Moonis, M; Chou, T C; Hirsch, M S

    1994-01-01

    We compared the in vitro efficacies of two-, three-, and four-drug combinations given continuously or in alternating regimens against a clinical isolate of human immunodeficiency virus type 1. In H9 cells and peripheral blood mononuclear cells, at the drug concentrations used in this study, there was greater suppression of human immunodeficiency virus type 1 infection as the number of drugs in the regimen was increased from one to four simultaneously administered agents. Although alternating drug regimens were effective, they were not better than continuous administration of either single drugs or combinations of agents and were less effective than giving all drugs of an alternating regimen simultaneously. PMID:8031028

  8. The Autonomous Glycosylation of Large DNA Viruses.

    PubMed

    Piacente, Francesco; Gaglianone, Matteo; Laugieri, Maria Elena; Tonetti, Michela G

    2015-01-01

    Glycosylation of surface molecules is a key feature of several eukaryotic viruses, which use the host endoplasmic reticulum/Golgi apparatus to add carbohydrates to their nascent glycoproteins. In recent years, a newly discovered group of eukaryotic viruses, belonging to the Nucleo-Cytoplasmic Large DNA Virus (NCLDV) group, was shown to have several features that are typical of cellular organisms, including the presence of components of the glycosylation machinery. Starting from initial observations with the chlorovirus PBCV-1, enzymes for glycan biosynthesis have been later identified in other viruses; in particular in members of the Mimiviridae family. They include both the glycosyltransferases and other carbohydrate-modifying enzymes and the pathways for the biosynthesis of the rare monosaccharides that are found in the viral glycan structures. These findings, together with genome analysis of the newly-identified giant DNA viruses, indicate that the presence of glycogenes is widespread in several NCLDV families. The identification of autonomous viral glycosylation machinery leads to many questions about the origin of these pathways, the mechanisms of glycan production, and eventually their function in the viral replication cycle. The scope of this review is to highlight some of the recent results that have been obtained on the glycosylation systems of the large DNA viruses, with a special focus on the enzymes involved in nucleotide-sugar production. PMID:26690138

  9. The Autonomous Glycosylation of Large DNA Viruses

    PubMed Central

    Piacente, Francesco; Gaglianone, Matteo; Laugieri, Maria Elena; Tonetti, Michela G.

    2015-01-01

    Glycosylation of surface molecules is a key feature of several eukaryotic viruses, which use the host endoplasmic reticulum/Golgi apparatus to add carbohydrates to their nascent glycoproteins. In recent years, a newly discovered group of eukaryotic viruses, belonging to the Nucleo-Cytoplasmic Large DNA Virus (NCLDV) group, was shown to have several features that are typical of cellular organisms, including the presence of components of the glycosylation machinery. Starting from initial observations with the chlorovirus PBCV-1, enzymes for glycan biosynthesis have been later identified in other viruses; in particular in members of the Mimiviridae family. They include both the glycosyltransferases and other carbohydrate-modifying enzymes and the pathways for the biosynthesis of the rare monosaccharides that are found in the viral glycan structures. These findings, together with genome analysis of the newly-identified giant DNA viruses, indicate that the presence of glycogenes is widespread in several NCLDV families. The identification of autonomous viral glycosylation machinery leads to many questions about the origin of these pathways, the mechanisms of glycan production, and eventually their function in the viral replication cycle. The scope of this review is to highlight some of the recent results that have been obtained on the glycosylation systems of the large DNA viruses, with a special focus on the enzymes involved in nucleotide-sugar production. PMID:26690138

  10. Determinants of Human Immunodeficiency Virus Type 1 Resistance to gp41-Derived Inhibitory Peptides

    PubMed Central

    Rimsky, Laurence T.; Shugars, Diane C.; Matthews, Thomas J.

    1998-01-01

    A synthetic peptide, DP178, containing amino acids 127 to 162 of the human immunodeficiency virus type 1 (HIV-1) gp41 Env glycoprotein, is a potent inhibitor of virus infection and virus mediated cell-to-cell fusion (C. Wild, T. Greenwell, and T. Matthews, AIDS Res. Hum. Retroviruses 9:1051–1053, 1993). In an effort to understand the mechanism of action of this peptide, we derived resistant variants of HIV-1IIIB and NL4-3 by serial virus passage in the presence of increasing doses of the peptide. Sequence analysis of the resistant isolates suggested that a contiguous 3-amino-acid sequence within the amino-terminal heptad repeat motif of gp41 was associated with resistance. Site-directed mutagenesis studies confirmed this observation and indicated that changes in two of these three residues were necessary for development of the resistant phenotype. Direct binding of DP178 to recombinant protein and synthetic peptide analogs containing the wild-type and mutant heptad repeat sequences revealed a strong correlation between DP178 binding and the biological sensitivity of the corresponding virus isolates to DP178. The results are discussed from the standpoints of the mechanism of action of DP178 and recent crystallographic information for a core structure of the gp41 ectodomain. PMID:9444991

  11. Molecular and biological characterization of a neurovirulent molecular clone of simian immunodeficiency virus.

    PubMed Central

    Flaherty, M T; Hauer, D A; Mankowski, J L; Zink, M C; Clements, J E

    1997-01-01

    To identify the molecular determinants of neurovirulence, we constructed an infectious simian immunodeficiency virus (SIV) molecular clone, SIV/17E-Fr, that contained the 3' end of a neurovirulent strain of SIV, SIV/17E-Br, derived by in vivo virus passage. SIV/17E-Fr is macrophage tropic in vitro and neurovirulent in macaques. In contrast, a molecular clone, SIV/17E-Cl, that contains the SU and a portion of the TM sequences of SIV/17E-Br is macrophage tropic but not neurovirulent. To identify the amino acids that accounted for the replication differences between SIV/17E-Fr and SIV/17E-Cl in primary macaque cells in vitro, additional infectious molecular clones were constructed. Analysis of these recombinant viruses revealed that changes in the TM portion of the envelope protein were required for the highest level of replication in primary macaque macrophages and brain cells derived from the microvessel endothelium. In addition, a full-length Nef protein is necessary for optimum virus replication in both of these cell types. Finally, viruses expressing a full-length Nef protein in conjunction with the changes in the TM had the highest specific infectivity in a sMAGI assay. Thus, changes in the TM and nef genes between SIV/17E-Cl and SIV/17E-Fr account for replication differences in vitro and correlate with replication in the central nervous system in vivo. PMID:9223467

  12. 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.

  13. Human Discs Large Is a New Negative Regulator of Human Immunodeficiency Virus-1 Infectivity

    PubMed Central

    Perugi, Fabien; Muriaux, Delphine; Ramirez, Bertha Cecilia; Chabani, Sabah; Decroly, Etienne; Darlix, Jean-Luc; Blot, Vincent

    2009-01-01

    Human immunodeficiency virus (HIV)-1 replication is positively or negatively regulated through multiple interactions with host cell proteins. We report here that human Discs Large (Dlg1), a scaffold protein recruited beneath the plasma membrane and involved in the assembly of multiprotein complexes, restricts HIV-1 infectivity. The endogenous Dlg1 and HIV-1 Gag polyprotein spontaneously interact in HIV-1-chronically infected T cells. Depleting endogenous Dlg1 in either adherent cells or T cells does not affect Gag maturation, production, or release, but it enhances the infectivity of progeny viruses five- to sixfold. Conversely, overexpression of Dlg1 reduces virus infectivity by ∼80%. Higher virus infectivity upon Dlg1 depletion correlates with increased Env content in cells and virions, whereas the amount of virus-associated Gag or genomic RNA remains identical. Dlg1 knockdown is also associated with the redistribution and colocalization of Gag and Env toward CD63 and CD82 positive vesicle-like structures, including structures that seem to still be connected to the plasma membrane. This study identifies both a new negative regulator that targets the very late steps of the HIV-1 life cycle, and an assembly pathway that optimizes HIV-1 infectivity. PMID:18946087

  14. Role of TAR RNA splicing in translational regulation of simian immunodeficiency virus from rhesus macaques.

    PubMed Central

    Viglianti, G A; Rubinstein, E P; Graves, K L

    1992-01-01

    The untranslated leader sequences of rhesus macaque simian immunodeficiency virus mRNAs form a stable secondary structure, TAR. This structure can be modified by RNA splicing. In this study, the role of TAR splicing in virus replication was investigated. The proportion of viral RNAs containing a spliced TAR structure is high early after infection and decreases at later times. Moreover, proviruses containing mutations which prevent TAR splicing are significantly delayed in replication. These mutant viruses require approximately 20 days to achieve half-maximal virus production, in contrast to wild-type viruses, which require approximately 8 days. We attribute this delay to the inefficient translation of unspliced-TAR-containing mRNAs. The molecular basis for this translational effect was examined in in vitro assays. We found that spliced-TAR-containing mRNAs were translated up to 8.5 times more efficiently than were similar mRNAs containing an unspliced TAR leader. Furthermore, these spliced-TAR-containing mRNAs were more efficiently associated with ribosomes. We postulate that the level of TAR splicing provides a balance for the optimal expression of both viral proteins and genomic RNA and therefore ultimately controls the production of infectious virions. Images PMID:1629957

  15. 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.

  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. Human immunodeficiency virus and hepatitis C co-infection in sub-Saharan West Africa.

    PubMed

    Mboto, C I; Davies, A; Fielder, M; Jewell, A P

    2006-01-01

    Co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is becoming a major global problem, leading to increased morbidity and mortality in developed countries. Co-existence in sub-Saharan West Africa of a high prevalence of HIV and HCV, which share similar behavioural risk factors and modes of transmission, must be seen in the broader context of an emerging third epidemic of HIV and HCV co-infection, as many factors that may affect the spread of HIV and HCV co-infection are endemic in the continent, including host factors such as sexual behaviour, presence of other sexually transmitted diseases, female and male circumcision status, percutaneous and perinatal exposure, and poverty. This review examines the epidemiology, risk factors and transmission of HIV and HCV co-infection and draws attention to the possible emergence of an epidemic of HIV and HCV co-infection in the region. PMID:16613141

  18. Feline immunodeficiency virus testing in stray, feral, and client-owned cats of Ottawa.

    PubMed

    Little, Susan E

    2005-10-01

    Feline immunodeficiency virus (FIV) seroprevalence is evaluated in 3 groups of cats. Seventy-four unowned urban strays were tested, as well as 20 cats from a small feral cat colony, and 152 client-owned cats. Of the 246 cats tested, 161 (65%) were male and 85 (35%) were female. Seroprevalence for FIV was 23% in the urban strays, 5% in the feral cat colony, and 5.9% in the client-owned cats. Ten cats (4%) were also positive for Feline leukemia virus (FeLV) antigen, including 2 cats coinfected with FeLV and FIV. Seroprevalence for FIV in cats from Ottawa is similar to that found in other nonrandom studies of cats in North America. PMID:16454381

  19. 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

  20. 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

  1. 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

  2. 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

  3. Role of the cytoskeleton in cell-to-cell transmission of human immunodeficiency virus.

    PubMed Central

    Pearce-Pratt, R; Malamud, D; Phillips, D M

    1994-01-01

    We previously observed that when human immunodeficiency virus (HIV)-infected T lymphocytes are added to epithelial cells, they adhere, polarize, and secrete virions unidirectionally onto the epithelium. Epithelial cells subsequently take up virus and become productively infected. We report here that colchicine treatment of T-lymphocyte suspensions induced lymphocyte polarization, redistribution of F-actin into a pseudopod, and secretion of HIV from the pseudopod. Immobilization of T lymphocytes on negatively charged plastic also caused redistribution of F-actin and unidirectional secretion of HIV onto the plastic. As neither colchicine nor adhesion caused an increase in HIV secretion, they apparently act by focusing secretion to the tip of the pseudopod. We speculate that adhesion-induced polar secretion of HIV, from activated mononuclear cells onto epithelia, is a cytoskeleton-mediated process which may be involved in HIV transmission in vivo. Images PMID:8151760

  4. Visualization and quantification of simian immunodeficiency virus-infected cells using non-invasive molecular imaging.

    PubMed

    Song, Jiasheng; Cai, Zhengxin; White, Alexander G; Jin, Tao; Wang, Xiaolei; Kadayakkara, Deepak; Anderson, Carolyn J; Ambrose, Zandrea; Young, Won-Bin

    2015-10-01

    In vivo imaging can provide real-time information and three-dimensional (3D) non-invasive images of deep tissues and organs, including the brain, whilst allowing longitudinal observation of the same animals, thus eliminating potential variation between subjects. Current in vivo imaging technologies, such as magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT) and bioluminescence imaging (BLI), can be used to pinpoint the spatial location of target cells, which is urgently needed for revealing human immunodeficiency virus (HIV) dissemination in real-time and HIV-1 reservoirs during suppressive antiretroviral therapy (ART). To demonstrate that in vivo imaging can be used to visualize and quantify simian immunodeficiency virus (SIV)-transduced cells, we genetically engineered SIV to carry different imaging reporters. Based on the expression of the reporter genes, we could visualize and quantify the SIV-transduced cells via vesicular stomatitis virus glycoprotein pseudotyping in a mouse model using BLI, PET-CT or MRI. We also engineered a chimeric EcoSIV for in vivo infection study. Our results demonstrated that BLI is sensitive enough to detect as few as five single cells transduced with virus, whilst PET-CT can provide 3D images of the spatial location of as few as 10 000 SIV-infected cells. We also demonstrated that MRI can provide images with high spatial resolution in a 3D anatomical context to distinguish a small population of SIV-transduced cells. The in vivo imaging platform described here can potentially serve as a powerful tool to visualize lentiviral infection, including when and where viraemia rebounds, and how reservoirs are formed and maintained during latency or suppressive ART. PMID:26297664

  5. Comparison of Immunity Generated by Nucleic Acid-, MF59-, and ISCOM-Formulated Human Immunodeficiency Virus Type 1 Vaccines in Rhesus Macaques: Evidence for Viral Clearance

    PubMed Central

    Verschoor, Ernst J.; Mooij, Petra; Oostermeijer, Herman; van der Kolk, Mike; ten Haaft, Peter; Verstrepen, Babs; Sun, Yide; Morein, Bror; Åkerblom, Lennart; Fuller, Deborah H.; Barnett, Susan W.; Heeney, Jonathan L.

    1999-01-01

    The kinetics of T-helper immune responses generated in 16 mature outbred rhesus monkeys (Macaca mulatta) within a 10-month period by three different human immunodeficiency virus type 1 (HIV-1) vaccine strategies were compared. Immune responses to monomeric recombinant gp120SF2 (rgp120) when the protein was expressed in vivo by DNA immunization or when it was delivered as a subunit protein vaccine formulated either with the MF59 adjuvant or by incorporation into immune-stimulating complexes (ISCOMs) were compared. Virus-neutralizing antibodies (NA) against HIV-1SF2 reached similar titers in the two rgp120SF2 protein-immunized groups, but the responses showed different kinetics, while NA were delayed and their levels were low in the DNA-immunized animals. Antigen-specific gamma interferon (IFN-γ) T-helper (type 1-like) responses were detected in the DNA-immunized group, but only after the fourth immunization, and the rgp120/MF59 group generated both IFN-γ and interleukin-4 (IL-4) (type 2-like) responses that appeared after the third immunization. In contrast, rgp120/ISCOM-immunized animals rapidly developed marked IL-2, IFN-γ (type 1-like), and IL-4 responses that peaked after the second immunization. To determine which type of immune responses correlated with protection from infection, all animals were challenged intravenously with 50 50% infective doses of a rhesus cell-propagated, in vivo-titrated stock of a chimeric simian immunodeficiency virus-HIVSF13 construct. Protection was observed in the two groups receiving the rgp120 subunit vaccines. Half of the animals in the ISCOM group were completely protected from infection. In other subunit vaccinees there was evidence by multiple assays that virus detected at 2 weeks postchallenge was effectively cleared. Early induction of potent type 1- as well as type 2-like T-helper responses induced the most-effective immunity. PMID:10074183

  6. 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 virus (HIV) in many respects. Similarities include the structural features of the virion, the general organization and great variability of the genome, the life cycle in the infected host, and most importantly, the pathogenic potential. Infection is associated with laboratory signs of immunosuppression as well as with a large variety of superinfections, tumors, and neurological manifestations. Our understanding of FIV is steadily improving and is providing important clues to the pathogenesis of immunodeficiency-inducing lentiviruses. The cellular receptor for FIV is different from the feline equivalent of the human CD4 molecule used by HIV; nevertheless, the major hallmark of infection is a progressive loss of CD4+ T lymphocytes as in HIV infection. The mechanisms by which FIV escapes the host's immune responses are being actively investigated. FIV causes lysis of infected T cells and also appears to predispose these cells to apoptosis. Infection of macrophages and other cell types has also been documented. For reasons yet to be understood, antibody-mediated neutralization of fresh FIV isolates is very inefficient both in vitro and in vivo. Vaccination studies have provided some encouraging results, but the difficulties encountered appear to match those met in HIV vaccine development. FIV susceptibility to antiviral agents is similar to that of HIV, thus providing a valuable system for in vivo preclinical evaluation of therapies. It is concluded that in many respects FIV is an ideal model for AIDS studies. PMID:7704896

  7. A Patient Presenting with Tuberculous Encephalopathy and Human Immunodeficiency Virus Infection

    PubMed Central

    Li, Jason; Afroz, Suraiya; French, Eric; Mehta, Anuj

    2016-01-01

    Patient: Male, 33 Final Diagnosis: Tuberculous meningitis, human immunodeficiency virus infection Symptoms: — Medication: — Clinical Procedure: Lumbar puncture Specialty: Infectious Diseases Objective: Rare disease Background: In the USA, Mycobacterium tuberculosis infection is more likely to be found in foreign-born individuals, and those co-infected with human immunodeficiency virus (HIV) are more likely to have tuberculous meningitis. The literature is lacking in details about the clinical workup of patients presenting with tuberculous meningitis with encephalopathic features who are co-infected with HIV. This report demonstrates a clinical approach to diagnosis and management of tuberculous meningitis. Case Report: A 33-year-old Ecuadorean man presented with altered consciousness and constitutional symptoms. During the workup he was found to have tuberculous meningitis with encephalopathic features and concurrent HIV infection. Early evidence for tuberculosis meningitis included lymphocytic pleocytosis and a positive interferon gamma release assay. A confirmatory diagnosis of systemic infection was made based on lymph node biopsy. Imaging studies of the neck showed scrofula and adenopathy, and brain imaging showed infarctions, exudates, and communicating hydrocephalus. Treatment was started for tuberculous meningitis, while antiretroviral therapy for HIV was started 5 days later in combination with prednisone, given the risk of immune reconstitution inflammatory syndrome (IRIS). Conclusions: A clinical picture consistent with tuberculous meningitis includes constitutional symptoms, foreign birth, lymphocytic pleocytosis, specific radiographic findings, and immunodeficiency. Workup for tuberculous meningitis should include MRI, HIV screening, and cerebral spinal fluid analysis. It is essential to treat co-infection with HIV and to assess for IRIS. PMID:27302013

  8. Gut epithelial barrier dysfunction in human immunodeficiency virus-hepatitis C virus coinfected patients: Influence on innate and acquired immunity

    PubMed Central

    Márquez, Mercedes; Fernández Gutiérrez del Álamo, Clotilde; Girón-González, José Antonio

    2016-01-01

    Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus (HIV)-infected patients have several non-acquired immunodeficiency syndrome (AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus (HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed. PMID:26819512

  9. Unraveling the Pathogenesis of HIV Peripheral Neuropathy: Insights from a Simian Immunodeficiency Virus Macaque Model

    PubMed Central

    Mangus, Lisa M.; Dorsey, Jamie L.; Laast, Victoria A.; Ringkamp, Matthias; Ebenezer, Gigi J.; Hauer, Peter; Mankowski, Joseph L.

    2014-01-01

    Peripheral neuropathy (PN) is the most frequent neurologic complication in individuals infected with human immunodeficiency virus (HIV). It affects over one third of infected patients, including those receiving effective combination antiretroviral therapy. The pathogenesis of HIV-associated peripheral neuropathy (HIV-PN) remains poorly understood. Clinical studies are complicated because both HIV and antiretroviral treatment cause damage to the peripheral nervous system. To study HIV-induced peripheral nervous system (PNS) damage, a unique simian immunodeficiency virus (SIV)/pigtailed macaque model of HIV-PN that enabled detailed morphologic and functional evaluation of the somatosensory pathway throughout disease progression was developed. Studies in this model have demonstrated that SIV induces key pathologic features that closely resemble HIV-induced alterations, including inflammation and damage to the neuronal cell bodies in somatosensory ganglia and decreased epidermal nerve fiber density. Insights generated in the model include: finding that SIV alters the conduction properties of small, unmyelinated peripheral nerves; and that SIV impairs peripheral nerve regeneration. This review will highlight the major findings in the SIV-infected pigtailed macaque model of HIV-PN, and will illustrate the great value of a reliable large animal model to show the pathogenesis of this complex, HIV-induced disorder of the PNS. PMID:24615443

  10. Prediction of optimal peptide mixtures to induce broadly neutralizing antibodies to human immunodeficiency virus type 1.

    PubMed Central

    Holley, L H; Goudsmit, J; Karplus, M

    1991-01-01

    Sequences of the principal neutralizing determinant (PND) of the external envelope protein, gp120, from 245 isolates of human immunodeficiency virus type 1 are analyzed. The minimal set of peptides that would elicit antibodies to neutralize a majority of U.S. and European isolates of human immunodeficiency virus type 1 is determined with the assumption that peptides of a given length including the central Gly-Pro-Gly triad are required. In spite of the hypervariability of the PND, 90% of these 245 sequences include peptides from a set of 7 pentapeptides, 13 hexapeptides, or 17 heptapeptides. Tests of these peptide sets on 78 additional PND sequences show that 95% are covered by the 7 pentapeptides, 94% by the 13 hexapeptides, and 86% by the 17 heptapeptides. To anticipate variants not yet observed, single amino acid mutation frequencies from the 245 isolates are used to calculate an expanded set of the 10,000 most probable PND sequences. These sequences cover 86% of the total distribution expected for the central portion of the PND. Peptide lists derived from this expanded set when tested on the 78 additional sequences show that 7 pentapeptides cover 95%, 13 hexapeptides cover 94%, and 17 heptapeptides cover 94%. These results suggest that peptide cocktails of limited size with the potential to cover a large fraction of PND sequence variation may be feasible vaccine candidates. PMID:1862103

  11. Antigenic stimulation specifically reactivates the replication of archived simian immunodeficiency virus genomes in chronically infected macaques.

    PubMed

    Renoux, Céline; Wain-Hobson, Simon; Hurtrel, Bruno; Cheynier, Rémi

    2005-09-01

    Human immunodeficiency virus/simian immunodeficiency virus (SIV) diversification is a direct consequence of viral replication and occurs principally in secondary lymphoid organs where CD4(+) T cells are activated and proliferate. However, the evolution of viral quasispecies may also be driven by various nonexclusive mechanisms, including adaptation to specific immune responses and modification of viral fitness. Analysis of viral quasispecies in SIV-infected macaques subjected to repeated antigenic stimulations allowed us to demonstrate transient expansions of SIV populations that were highly dependent upon activation of antigen-specific T cells. T-cell clones expanded in response to a particular antigen were infected by a specific viral population and persisted for prolonged periods. Upon a second stimulation by encounter with the same antigen, these specific genomes were at the origin of a new burst of replication, leading to rapid but transient replacement of the viral quasispecies in blood. Finally, longitudinal analysis of SIV sequence variation during and between antigenic stimulations revealed that viral evolution is mostly constrained to periods of strong immunological activity. PMID:16103175

  12. RNase H activity associated with reverse transcriptase from feline immunodeficiency virus.

    PubMed Central

    Cronn, R C; Whitmer, J D; North, T W

    1992-01-01

    Reverse transcription of retroviral genomes requires the action of an RNase H for template switching and primer generation. In this report, we compare enzymatic properties of the RNase H associated with the reverse transcriptase (RT) from feline immunodeficiency virus (FIV) and that from human immunodeficiency virus (HIV). Both enzymes displayed substrate preference for poly[3H](rG) . poly(dC) hybird over poly[3H](rA) . poly(dT) and cation preference for Mg2+ over Mn2+. Activity of the FIV RNase H upon poly(rG) . poly(dC) produced hydrolysis products from 1 to 6 nucleotides in length, similar to that reported for HIV. Dextran sulfates were effective inhibitors of both the FIV and HIV RNase H and RT activities. Nearly identical inhibition constants (0.12 nM) were obtained for all enzyme activities with dextran sulfate 500,000, while different inhibition constants were observed with dextran sulfate 8,000. Our results suggest that FIV and HIV RTs contain a conserved region that is sensitive to the larger dextran sulfate and that dextran sulfate 8,000 may interact at a different site or by a different mechanism. Images PMID:1370549

  13. Two Orphan Seven-Transmembrane Segment Receptors Which Are Expressed in CD4-positive Cells Support Simian Immunodeficiency Virus Infection

    PubMed Central

    Farzan, Michael; Choe, Hyeryun; Martin, Kathleen; Marcon, Luisa; Hofmann, Wolfgang; Karlsson, Gunilla; Sun, Ying; Barrett, Peter; Marchand, Nathalie; Sullivan, Nancy; Gerard, Norma; Gerard, Craig; Sodroski, Joseph

    1997-01-01

    Clinical isolates of primate immunodeficiency viruses, including human immunodeficiency virus type 1 (HIV-1), enter target cells by sequential binding to CD4 and the chemokine receptor CCR5, a member of the seven-transmembrane receptor family. HIV-1 variants which use additional chemokine receptors are present in the central nervous system or emerge during the course of infection. Simian immunodeficiency viruses (SIV) have been shown to use CCR5 as a coreceptor, but no other receptors for these viruses have been identified. Here we show that two orphan seven-transmembrane segment receptors, gpr1 and gpr15, serve as coreceptors for SIV, and are expressed in human alveolar macrophages. The more efficient of these, gpr15, is also expressed in human CD4+ T lymphocytes and activated rhesus macaque peripheral blood mononuclear cells. The gpr15 and gpr1 proteins lack several hallmarks of chemokine receptors, but share with CCR5 an amino-terminal motif rich in tyrosine residues. These results underscore the potential diversity of seven-transmembrane segment receptors used as entry cofactors by primate immunodeficiency viruses, and may contribute to an understanding of viral variation and pathogenesis. PMID:9236192

  14. Induction of human interferon gene expression is associated with a nuclear factor that interacts with the site of the human immunodeficiency virus-enhancer

    SciTech Connect

    Hiscott, J.; Alper, D.; Cohen, L.; Leblanc, J.F.; Sportza, L.; Wong, A.; Xanthoudakis, S. )

    1989-06-01

    The relationship between transcription of alpha and beta interferon (IFN-{alpha} and IFN-{beta}) genes and the interaction of IFN promoter-binding transcription factors has been examined in monoblastoid U937 cells following priming with recombinant IFN-{alpha}2 (rIFN-{alpha}2) and Sendai virus induction. Pretreatment of U937 cells with rIFN-{alpha}2 prior to Sendai virus infection increased the mRNA levels of IFN-{alpha}1, IFN-{alpha}2, and IFN-{beta} as well as the final yield of biologically active IFN. Analysis of nuclear protein-IFN promoter DNA interactions by electrophoretic mobility-shift assays demonstrated increased factor binding to IFN-{alpha}1 and IFN-{beta} regulatory domains, although no new induction-specific complexes were identified. On the basis of competition electrophoretic mobility-shift assay results, factors interacting with the IFN-{alpha}1 and IFN-{beta} promoters appear to be distinct DNA-binding proteins. Hybrid promoter-chloramphenicol acetyltransferase fusion plasmids, containing either the IFN-{beta} regulatory element or the human immunodeficiency virus enhancer element linked to the simian virus 40 promoter, were analyzed for virus and phorbol ester inducibility in epithelial and lymphoid cells, respectively. These experiments suggest that induction of IFN gene expression may be controlled in part by transcription regulatory proteins binding to an NF-{kappa}B-like site within the IFN-{beta} promoter.

  15. Primary immunodeficiency syndromes associated with defective DNA double-strand break repair.

    PubMed

    Gennery, A R

    2006-01-01

    Damaging DNA double-strand breaks (DNA-DSBs) following ionizing radiation (IR) exposure, potentially lead to cell death or carcinogenesis. Non-homologous end-joining (NHEJ) is the main repair pathway employed by vertebrate cells to repair such damage. Many repair pathway proteins have been identified. The creation of many diverse lymphocyte receptors to identify potential pathogens has evolved by breaking and randomly re-sorting the gene segments coding for antigen receptors. Subsequent DNA-DSB repair utilizes the NHEJ proteins. Individuals with defective repair pathways are increasingly recognized with radiosensitivity and immunodeficiency. Patients with defects in ataxia-telangiectasia mutated, nibrin, MRE11, Rad50, Artemis, DNA ligase IV and Cernunnos-XRCC4-like factor have been identified. Most exhibit immunodeficiency, with a spectrum of presentation and overlap between conditions. Conventional treatment with immunoglobulin replacement or haematopoietic stem cell transplantation (HSCT) can be effective. A greater understanding of the molecular defect will enable better, tailored therapies to improve survival. PMID:16971555

  16. An env gene derived from a primary human immunodeficiency virus type 1 isolate confers high in vivo replicative capacity to a chimeric simian/human immunodeficiency virus in rhesus monkeys.

    PubMed Central

    Reimann, K A; Li, J T; Voss, G; Lekutis, C; Tenner-Racz, K; Racz, P; Lin, W; Montefiori, D C; Lee-Parritz, D E; Lu, Y; Collman, R G; Sodroski, J; Letvin, N L

    1996-01-01

    To explore the roles played by specific human immunodeficiency virus type 1 (HIV-1) genes in determining the in vivo replicative capacity of AIDS viruses, we have examined the replication kinetics and virus-specific immune responses in rhesus monkeys following infection with two chimeric simian/human immunodeficiency viruses (SHIVs). These viruses were composed of simian immunodeficiency virus SIVmac239 expressing HIV-1 env and the associated auxiliary HIV-1 genes tat, vpu, and rep. Virus replication was assessed during primary infection of rhesus monkeys by measuring plasma SIVmac p27 levels and by quantifying virus replication in lymph nodes using in situ hybridization. SHIV-HXBc2, which expresses the HIV-1 env of a T-cell-tropic, laboratory-adapted strain of HIV-1 (HXBc2), replicated well in rhesus monkey peripheral blood leukocytes (PBL) in vitro but replicated only to low levels when inoculated in rhesus monkeys. In contrast, SHIV-89.6 was constructed with the HIV-1 env gene of a T-cell- and macrophage-tropic clone of a patient isolate of HIV-1 (89.6). This virus replicated to a lower level in monkey PBL in vitro but replicated to a higher degree in monkeys during primary infection. Moreover, monkeys infected with SHIV-89.6 developed an inversion in the PBL CD4/CD8 ratio coincident with the clearance of primary viremia. The differences in the in vivo consequences of infection by these two SHIVs could not be explained by differences in the immune responses elicited by these viruses, since infected animals had comparable type-specific neutralizing antibody titers, proliferative responses to recombinant HIV-1 gp120, and virus-specific cytolytic effector T-cell responses. With the demonstration that a chimeric SHIV can replicate to high levels during primary infection in rhesus monkeys, this model can now be used to define genetic determinants of HIV-1 pathogenicity. PMID:8627800

  17. Effects of gamma rays, ultraviolet radiation, sunlight, microwaves and electromagnetic fields on gene expression mediated by human immunodeficiency virus promoter

    SciTech Connect

    Libertin, C.R.; Woloschak, G.E. |; Panozzo, J.; Groh, K.R.; Chang-Liu, Chin-Mei; Schreck, S.

    1994-10-01

    Previous work by our group and others has shown the modulation of human immunodeficiency virus (HIV) promoter or long terminal repeat (LTR) after exposure to neutrons and ultraviolet radiations. Using HeLa cells stably transfected with a construct containing the chloramphenicol acetyl transferase (CAT) gene, the transcription of which is mediated by the HIV-LTR, we designed experiments to examine the effects of exposure to different types of radiation (such as {gamma} rays, ultraviolet and sunlight irradiations, electromagnetic fields and microwaves) in HIV-LTR-driven expression of CAT. These results demonstrated ultraviolet-light-induced transcription from the HIV promoter, as has been shown by others. Exposure to other DNA-damaging agents such as {gamma} rays and sunlight (with limited exposures) had no significant effect on transcription mediated by HIV-LTR, suggesting that induction of HIV is not mediated by just any type of DNA damage but rather may require specific types of DNA damage. Microwaves did not cause cell killing when cells in culture were exposed in high volumes of medium, and the same cells showed no changes in expression. When microwave exposure was carried out in low volumes of medium (so that excessive heat was generated) induction of HIV-LTR transcription (as assayed by CAT activity) was evident. Electromagnetic field exposures had no effect on expression of HIV-LTR. These results demonstrate that not all types of radiation and not all DNA-damaging agents are capable of inducing HIV. We hypothesize that induction of HIV transcription may be mediated by several different signals exposure to radiation. 22 refs., 8 figs.

  18. Zinc Finger Structures in the Human Immunodeficiency Virus Type 1 Nucleocapsid Protein Facilitate Efficient Minus- and Plus-Strand Transfer

    PubMed Central

    Guo, Jianhui; Wu, Tiyun; Anderson, Jada; Kane, Bradley F.; Johnson, Donald G.; Gorelick, Robert J.; Henderson, Louis E.; Levin, Judith G.

    2000-01-01

    The nucleocapsid protein (NC) of human immunodeficiency virus type 1 (HIV-1) has two zinc fingers, each containing the invariant metal ion binding residues CCHC. Recent reports indicate that mutations in the CCHC motifs are deleterious for reverse transcription in vivo. To identify reverse transcriptase (RT) reactions affected by such changes, we have probed zinc finger functions in NC-dependent RT-catalyzed HIV-1 minus- and plus-strand transfer model systems. Our approach was to examine the activities of wild-type NC and a mutant in which all six cysteine residues were replaced by serine (SSHS NC); this mutation severely disrupts zinc coordination. We find that the zinc fingers contribute to the role of NC in complete tRNA primer removal from minus-strand DNA during plus-strand transfer. Annealing of the primer binding site sequences in plus-strand strong-stop DNA [(+) SSDNA] to its complement in minus-strand acceptor DNA is not dependent on NC zinc fingers. In contrast, the rate of annealing of the complementary R regions in (−) SSDNA and 3′ viral RNA during minus-strand transfer is approximately eightfold lower when SSHS NC is used in place of wild-type NC. Moreover, unlike wild-type NC, SSHS NC has only a small stimulatory effect on minus-strand transfer and is essentially unable to block TAR-induced self-priming from (−) SSDNA. Our results strongly suggest that NC zinc finger structures are needed to unfold highly structured RNA and DNA strand transfer intermediates. Thus, it appears that in these cases, zinc finger interactions are important components of NC nucleic acid chaperone activity. PMID:10982342

  19. Effect of a cellulose acetate phthalate topical cream on vaginal transmission of simian immunodeficiency virus in rhesus monkeys.

    PubMed

    Manson, K H; Wyand, M S; Miller, C; Neurath, A R

    2000-11-01

    Human immunodeficiency virus type 1 (HIV-1) infection continues to spread in developing countries, mostly through heterosexual transmission. The development of a safe and cost-effective topical microbicide, effective against a range of STDs including HIV-1, would greatly impact the ongoing epidemic. When formulated in a vehicle, a micronized form of cellulose acetate phthalate (CAP), which is an inactive pharmaceutical excipient, has been shown to inactivate HIV-1, herpes simplex virus types 1 and 2, cytomegalovirus, Neisseria gonorrhoeae, Trichomonas vaginalis, Haemophilus ducreyi, and Chlamydia trachomatis in vitro. Formulated CAP was also shown to be effective against herpes simplex virus type 2 in vivo. Here we show that a formulation of CAP protected four of six rhesus monkeys from vaginal infection with simian immunodeficiency virus. Thus, CAP may be a candidate for use as a topical microbicide for preventing HIV-1 infection in humans. PMID:11036053

  20. Simian Immunodeficiency Virus Variants That Differ in Pathogenicity Differ in Fitness under Rapid Cell Turnover Conditions

    PubMed Central

    Voronin, Yegor; Overbaugh, Julie; Emerman, Michael

    2005-01-01

    Simian immunodeficiency virus (SIV) has been shown to progress through a number of changes that lead to the emergence of pathogenic viral variants in macaques initially infected with a mildly cytopathic variant, SIVMneCL8. One of these late-stage isolates, SIVMne170, replicates to high levels in vivo and causes a rapid disease course when reintroduced into naïve macaques, resulting in a viral set point up to 3,000-fold higher than the set point of the parental virus, SIVMneCL8. However, in cell culture both viruses replicate with similar kinetics. One major difference between in vivo and in vitro cultures is the life span of the infected cells. Here, we manipulated the life span of infected cells in vitro, and we show that the fitness of SIVMne170 in cultures with a limited cell life span dramatically increased compared to its fitness in cultures with a nonlimited life span of cells. The increase in fitness was at least partially due to the fact that the rapid turnover system eliminates the negative influence of the cytopathic effects associated with replication of SIVMne170. Because the relative fitness of SIVMneCL8 and SIVMne170 observed in the rapid turnover system more accurately reflects their fitness in vivo, the system represents an improved approach to comparing relative fitness of viruses. PMID:16306580