Sample records for neutralizing anti-human immunodeficiency

  1. Effect of Epitope Position on Neutralization by Anti-Human Immunodeficiency Virus Monoclonal Antibody 2F5

    PubMed Central

    Ou, Wu; Lu, Ning; Yu, Sloane S.; Silver, Jonathan

    2006-01-01

    The membrane-proximal region of the human immunodeficiency virus type 1 (HIV-1) transmembrane protein (TM) is critical for envelope (Env)-mediated membrane fusion and contains the target for broadly reactive neutralizing antibody 2F5. It has been proposed that 2F5 neutralization might involve interaction of its long, hydrophobic, complementarity-determining region (CDR) H3, with adjacent viral membrane. Using Moloney murine leukemia virus (MLV) as a tool, we examined the effect of epitope position on 2F5 neutralization. When the 2F5 epitope was inserted in the proline-rich region of MLV Env surface protein (SU), 2F5 blocked cell fusion and virus infection, whereas MLV with a hemagglutinin (HA) epitope at the same position was not neutralized by anti-HA, even though the antibodies bound their respective Envs on the surface of infected cells and viruses equally well. When the 2F5 epitope was inserted in the MLV Env TM at a position comparable to its natural position in HIV-1 TM, 2F5 antibody blocked Env-mediated cell fusion. Epitope position had subtle effects on neutralization by 2F5: the antibody concentration for 50% inhibition of cell fusion was more than 10-fold lower when the 2F5 epitope was in SU than in TM, and inhibition was less complete at high concentrations of antibody; we discuss possible explanations for these effects of epitope position. Since membrane proximity was not required for neutralization by 2F5 antibody, we speculate that the CDR H3 of 2F5 contributes to neutralization by destabilizing an adjacent protein rather than by inserting into an adjacent membrane. PMID:16474160

  2. Structure-activity correlationship and strain specificity of polyoxometalates in anti-human immunodeficiency virus activity.

    PubMed

    Inouye, Y; Fujimoto, Y; Sugiyama, M; Yoshida, T; Yamase, T

    1995-07-01

    The anti-human immunodeficiency virus (HIV) activity of polyoxometalates of representative structural families, such as Keggin, lacunary Keggin, trivacant Keggin, Keggin sandwich, Wells-Dawson and Wells-Dawson sandwich, was determined using two strains of HIV type 1 (HIV-1HTLV-IIIB and HIV-1SF-2H). The compounds were preferably selected to cover both polyoxotungstates and polyoxomolybdates in each structural family. In general, polyoxotungstates of Keggin, lacunary Keggin, trivacant Keggin, Keggin sandwich, Wells-Dawson and Wells-Dawson sandwich structures showed anti-HIV-1HTLVIIIB activity, whereas most compounds not included in these structural categories were inactive. Among the compounds with a potent anti-HIV-1HTLV-IIIB activity, those of Keggin and its closely related structural families (lacunary Keggin, trivacant Keggin and Keggin sandwich) inhibited the cytopathogenicity and syncytium formation caused by HIV-1SF-2 to a much higher extent compared with HIV-1HTLV-IIIB-related ones. The difference between the spectra of anti-HIV-1HTLV-IIIB activity and the specificity for HIV-1SF-2H might result from differential structural requirements in these functions. PMID:7581257

  3. Feline immunodeficiency virus (FIV) neutralization: a review.

    PubMed

    Hosie, Margaret J; Pajek, Daniela; Samman, Ayman; Willett, Brian J

    2011-10-01

    One of the major obstacles that must be overcome in the design of effective lentiviral vaccines is the ability of lentiviruses to evolve in order to escape from neutralizing antibodies. The primary target for neutralizing antibodies is the highly variable viral envelope glycoprotein (Env), a glycoprotein that is essential for viral entry and comprises both variable and conserved regions. As a result of the complex trimeric nature of Env, there is steric hindrance of conserved epitopes required for receptor binding so that these are not accessible to antibodies. Instead, the humoral response is targeted towards decoy immunodominant epitopes on variable domains such as the third hypervariable loop (V3) of Env. For feline immunodeficiency virus (FIV), as well as the related human immunodeficiency virus-1 (HIV-1), little is known about the factors that lead to the development of broadly neutralizing antibodies. In cats infected with FIV and patients infected with HIV-1, only rarely are plasma samples found that contain antibodies capable of neutralizing isolates from other clades. In this review we examine the neutralizing response to FIV, comparing and contrasting with the response to HIV. We ask whether broadly neutralizing antibodies are induced by FIV infection and discuss the comparative value of studies of neutralizing antibodies in FIV infection for the development of more effective vaccine strategies against lentiviral infections in general, including HIV-1. PMID:22069520

  4. Multiple Effects of an Anti-Human Immunodeficiency Virus Nucleocapsid Inhibitor on Virus Morphology and Replication

    PubMed Central

    Berthoux, Lionel; Péchoux, Christine; Darlix, Jean-Luc

    1999-01-01

    Human immunodeficiency virus type 1 nucleocapsid protein is a major structural component of the virion core and a key factor involved in proviral DNA synthesis and virus formation. 2,2?-Dithiobenzamides (DIBA-1) and related compounds that are inhibitors of NCp7 are thought to eject zinc ions from NCp7 zinc fingers, inhibiting the maturation of virion proteins. Here, we show that the presence of DIBA-1 at the time of virus formation causes morphological malformations of the virus and reduces proviral DNA synthesis. Thus, it seems that DIBA-1 is responsible for a “core-freezing effect,” as shown by electron microscopy analyses. DIBA-1 can also directly interfere with the fate of the newly made proviral DNA in a manner independent of its effects on virion core formation. These data strongly suggest that nucleocapsid protein is a prime target for new compounds aimed at inhibiting human immunodeficiency virus and other retroviruses. PMID:10559314

  5. Induction of murine mucosal CCR5-reactive antibodies as an anti-human immunodeficiency virus strategy

    Microsoft Academic Search

    C. Barassi; E. Soprana; C. Pastori; R. Longhi; E. Buratti; F. Lillo; C. Marenzi; A. Lazzarin; A. G. Siccardi; L. Lopalco

    2005-01-01

    The genital mucosa is the main site of initial human immunodeficiency virus type 1 (HIV-1) contact with its host. In spite of repeated sexual exposure, some individuals remain seronegative, and a small fraction of them produce immunoglobulin G (IgG) and IgA autoantibodies directed against CCR5, which is probably the cause of the CCR5-minus phenotype observed in the peripheral blood mononuclear

  6. New Anti-Human Immunodeficiency Virus Type 1 6-Aminoquinolones: Mechanism of Action

    Microsoft Academic Search

    Cristina Parolin; Barbara Gatto; Claudia Del Vecchio; Teresa Pecere; Enzo Tramontano; Violetta Cecchetti; Arnaldo Fravolini; Sara Masiero; Manlio Palumbo; Giorgio Palu

    2003-01-01

    A 6-aminoquinolone derivative, WM5, which bears a methyl substituent at the N-1 position and a 4-(2- pyridyl)-1-piperazine moiety at position 7 of the bicyclic quinolone ring system, was previously shown to exhibit potent activity against replication of human immunodeficiency virus type 1 (HIV-1) in de novo-infected human lymphoblastoid cells (V. Cecchetti et al., J. Med. Chem. 43:3799-3802, 2000). In this

  7. Optimization of Azoles as Anti-Human Immunodeficiency Virus Agents Guided by Free-Energy Calculations

    PubMed Central

    Zeevaart, Jacob G.; Wang, Ligong; Thakur, Vinay V.; Leung, Cheryl S.; Tirado-Rives, Julian; Bailey, Christopher M.; Domaoal, Robert A.; Anderson, Karen S.; Jorgensen, William L.

    2009-01-01

    Efficient optimization of an inactive 2-anilinyl-5-benzyloxadiazole core has been guided by free energy perturbation (FEP) calculations to provide potent non-nucleoside inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (NNRTIs). An FEP “chlorine scan” was performed to identify the most promising sites for substitution of aryl hydrogens. This yielded NNRTIs 8 and 10 with activities (EC50) of 820 and 310 nM for protection of human T-cells from infection by wild-type HIV-1. FEP calculations for additional substituent modifications and change of the core heterocycle readily led to oxazoles 28 and 29, which were confirmed as highly potent anti-HIV agents with activities in the 10–20 nM range. The designed compounds were also monitored for possession of desirable pharmacological properties by use of additional computational tools. Overall, the trends predicted by the FEP calculations were well borne out by the assay results. FEP-guided lead optimization is confirmed as a valuable tool for molecular design including drug discovery; chlorine scans are particularly attractive since they are both straightforward to perform and highly informative. PMID:18588301

  8. Differential Effects of Interleukin7 and Interleukin15 on NK Cell Anti-Human Immunodeficiency Virus Activity

    Microsoft Academic Search

    Julian J. Lum; David J. Schnepple; Zilin Nie; Jaime Sanchez-Dardon; Georgina L. Mbisa; Jennifer Mihowich; Nanci Hawley; Shanil Narayan; John E. Kim; David H. Lynch; Andrew D. Badley

    2004-01-01

    The ability of interleukin-7 (IL-7) and IL-15 to expand and\\/or augment effector cell functions may be of therapeutic benefit to human immunodeficiency virus (HIV)-infected patients. The functional effects of these cytokines on innate HIV-specific immunity and their impact on cells harboring HIV are unknown. We demonstrate that both IL-7 and IL-15 augment natural killer (NK) function by using cells (CD3

  9. 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

  10. In vitro anti-human immunodeficiency virus (HIV) activity of XM323, a novel HIV protease inhibitor.

    PubMed Central

    Otto, M J; Reid, C D; Garber, S; Lam, P Y; Scarnati, H; Bacheler, L T; Rayner, M M; Winslow, D L

    1993-01-01

    XM323 represents a novel class of potent inhibitors of human immunodeficiency virus (HIV) protease. In vitro studies have shown that inhibition of this enzyme translates into potent inhibition of replication of HIV type 1 (HIV-1) and HIV-2. The inhibition of virus replication was assessed with three assays designed to measure the production of infectious virus, viral RNA, or p24 antigen. The production of mature infectious virions was measured with a yield reduction assay. By this assay, several strains and isolates of HIV-1 and HIV-2 were shown to be susceptible to XM323 in two lymphoid cell lines (MT-2 and H9) and in normal peripheral blood mononuclear cells, with a concentration required for 90% inhibition (IC90) of 0.12 +/- 0.04 microM (mean +/- standard deviation). The production of HIV-1(RF) RNA was measured with an RNA hybridization-capture assay. With this assay, XM323 was shown to be a potent inhibitor of HIV-1(RF) replication, with an IC90 of 0.063 +/- 0.032 microM. A third measure of virus replication, the production of p24 viral antigen, an essential protein component of the virion, was determined with the AIDS Clinical Trial Group-Department of Defense peripheral blood mononuclear cell consensus assay. This assay was used for expanded testing of XM323 against 28 clinical isolates and laboratory strains of HIV-1. XM323 was shown to be equally effective against zidovudine-susceptible and zidovudine-resistant isolates of HIV-1, with an overall IC90 of 0.16 +/- 0.06 microM. PMID:8109924

  11. Anti-human immunodeficiency virus type 1 activity of an anti-CD4 immunoconjugate containing pokeweed antiviral protein.

    PubMed Central

    Erice, A; Balfour, H H; Myers, D E; Leske, V L; Sannerud, K J; Kuebelbeck, V; Irvin, J D; Uckun, F M

    1993-01-01

    The ability of an alpha CD4-pokeweed antiviral protein (PAP) immunoconjugate to inhibit replication of human immunodeficiency virus type 1 (HIV-1) was evaluated in vitro with 22 clinical HIV-1 strains obtained from four seropositive asymptomatic individuals, three patients with AIDS-related complex, and four patients with AIDS. Fifteen isolates were from zidovudine-untreated individuals, whereas seven isolates were obtained after 24 to 104 weeks of therapy with zidovudine, alone or alternating with zalcitabine. Mean zidovudine 50% inhibitory concentrations (IC50s) were 126 nM (range, 1 to 607 nM) for isolates from zidovudine-untreated individuals and 2,498 nM (range, 14 to 6,497 nM) for strains from patients treated with antiretroviral agents. Mean alpha CD4-PAP IC50s were 48 x 10(-3) nM (range, 0.02 x 10(-3) to 212 x 10(-3) nM) for isolates from zidovudine-untreated individuals, and 16 x 10(-3) nM (range, 2 x 10(-3) to 28 x 10(-3) nM) for isolates from treated patients. Overall, higher concentrations of alpha CD4-PAP were necessary to inhibit HIV-1 strains from untreated individuals at more advanced stages of disease. Seventeen isolates were susceptible to zidovudine (mean IC50, 117 nM), and five were resistant to zidovudine (mean IC50, 3,724 nM). Mean alpha CD4-PAP IC50s were 43 x 10(-3) nM for zidovudine-susceptible isolates and 19 x 10(-3) nM for isolates resistant to zidovudine. All HIV-1 strains had IC50s greater than 0.5 nM for unconjugated PAP, the alpha CD19-PAP immunoconjugate, and monoclonal antibody alpha CD4. At concentrations as high as 5,000 nM, alphaCD4-PAP did not inhibit colony formation by normal bone marrow progenitor cells(BFU-E, CFU-GM , and CFU-GEMM) or myeloid cell lines (KG-1 and HL-60) and did not decrease cell viabilities of T-cell (Jurkat) or B-cell (FL-112 and Raji) precursor lines. Overall, alphaCD4-PAP demonstrated more potent anti-HIV-1 activity than zidovudine and inhibited replication of zidovudine-susceptible and zidovudine-resistant viruses at concentrations that were not toxic to lymphohematopoietic cell populations. PMID:8494381

  12. Comparison of the Phosphorylation of 4?-Ethynyl 2?,3?-Dihydro-3?-Deoxythymidine with That of Other Anti-Human Immunodeficiency Virus Thymidine Analogs?

    PubMed Central

    Hsu, Chih-Hung; Hu, Rong; Dutschman, Ginger E.; Yang, Guangwei; Krishnan, Preethi; Tanaka, Hiromichi; Baba, Masanori; Cheng, Yung-Chi

    2007-01-01

    Thymidine analogs, including 3?-azido-3?-deoxythymidine (AZT) and 2?,3?-dideoxy-3?-deoxythymidine (D4T), are important antiretroviral agents. To exert antiretroviral activity, these analogs undergo a stepwise phosphorylation intracellularly to the active triphosphate metabolites. We previously reported that 4?-substituted D4T with an ethynyl group (i.e., 4?-ethynyl D4T) increased the anti-human immunodeficiency virus (HIV) activity and was active against multidrug-resistant HIV strains. 4?-Ethynyl D4T is a better substrate for phosphorylation by human thymidine kinase 1 than D4T is. In this report, we first studied the enzymes involved in the phosphorylation of 4?-ethynyl D4T from monophosphate to triphosphate metabolites. The 4?-ethynyl D4TMP is phosphorylated by recombinant human TMP kinase with a Km of 19 ± 4 ?M and a kcat of 0.007 ± 0.001 s?1; the relative efficiency is about 9 and 15% of those of D4TMP and AZTMP, respectively. Several enzymes from crude cellular extracts, including nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, and 3-phosphoglycerate kinase, could phosphorylate 4?-ethynyl D4T-diphosphate. The relative phosphorylation efficiencies of 4?-ethynyl D4TDP were about 3 to 25% of those of D4TDP and were generally similar to those of AZTDP. In T-lymphoid cell lines, there was a preponderant accumulation of 4?-ethynyl D4TMP, suggesting that TMP kinase could be the rate-limiting enzyme in the metabolism of 4?-ethynyl D4T. Although the same enzymes are involved in the stepwise phosphorylation of thymidine analogs, their behaviors in phosphorylating metabolites of 4?-ethynyl D4T are different from those of D4T and AZT. Qualitatively, the metabolism of 4?-ethynyl D4T is more similar to that of AZT than to that of its progenitor, D4T. PMID:17353236

  13. In Vivo Toxicity, Pharmacokinetics, and Anti-Human Immunodeficiency Virus Activity of Stavudine-5?-(p-Bromophenyl Methoxyalaninyl Phosphate) (Stampidine) in Mice

    PubMed Central

    Uckun, Fatih M.; Qazi, Sanjive; Pendergrass, Sharon; Lisowski, Elizabeth; Waurzyniak, Barbara; Chen, Chun-Lin; Venkatachalam, T. K.

    2002-01-01

    We have evaluated the clinical potential of stavudine-5?-(p-bromophenyl methoxyalaninyl phosphate(stampidine [STAMP]), a novel aryl phosphate derivative of stavudine, as a new anti-human immunodeficiency virus (anti-HIV) agent, by examining its acute, subacute, and chronic toxicity profile in mice as well as by testing its antiviral activity in a surrogate human peripheral blood lymphocyte (Hu-PBL)-SCID mouse model of human AIDS. STAMP was very well tolerated in BALB/c and CD-1 mice, without any detectable acute or subacute toxicity at single intraperitoneal or oral bolus doses as high as 500 mg/kg of body weight. Notably, daily administration of STAMP intraperitoneally or orally for up to 8 consecutive weeks was not associated with any detectable toxicity at cumulative dose levels as high as 6.4 g/kg. Micromolar concentrations of the active STAMP metabolite in plasma were rapidly achieved and maintained for more than 4 h after parenteral as well as oral administration of a nontoxic 100-mg/kg bolus dose of STAMP. In accordance with its favorable pharmacokinetic profile and in vitro potency, STAMP exhibited dose-dependent and potent in vivo anti-HIV activity in Hu-PBL-SCID mice against a genotypically and phenotypically nucleoside analog reverse transcriptase inhibitor (NRTI)-resistant clinical HIV type 1 (HIV-1) isolate (BR/92/019; D67N, L214F, T215D, K219Q) at nontoxic dose levels. The remarkable in vivo safety and potency of STAMP warrants the further development of this promising new antiretroviral agent for possible clinical use in patients harboring NRTI-resistant HIV-1. PMID:12384347

  14. 5-Chloro-2',3'-dideoxy-3'-fluorouridine (935U83), a selective anti-human immunodeficiency virus agent with an improved metabolic and toxicological profile.

    PubMed

    Daluge, S M; Purifoy, D J; Savina, P M; St Clair, M H; Parry, N R; Dev, I K; Novak, P; Ayers, K M; Reardon, J E; Roberts, G B

    1994-07-01

    5-Chloro-2',3'-dideoxy-3'-fluorouridine (935U83) is a selective anti-human immunodeficiency virus (HIV) agent. When tested in phytohemagglutinin-stimulated normal human peripheral blood lymphocytes against fresh clinical isolates of HIV type 1 (HIV-1) obtained from patients naive to AZT (3'-azido-3'-deoxythymidine [zidovudine]), 935U83 inhibited virus growth with an average 50% inhibitory concentration (IC50) of 1.8 microM; corresponding IC50s were 0.10 microM for FLT (3'-deoxy-3'-fluorothymidine) and 0.23, 0.49, and 0.03 microM for the approved agents AZT, ddI (2',3'-dideoxyinosine), and ddC (2',3'-dideoxycytosine), respectively. Importantly, 935U83 retained activity against HIV strains that were resistant to AZT, ddI, or ddC. Of additional interest, we were unable to generate virus which was resistant to 935U83 by passaging either HXB2 (AZT-sensitive) or RTMC (AZT-resistant) strains in the presence of high concentrations of 935U83. The anabolic profile of 935U83 was similar to that of AZT, and 935U83 triphosphate was a potent inhibitor of HIV-1 reverse transcriptase. Pharmacokinetic evaluation showed good oral bioavailability (86% in mice and 60% in monkeys) and less extensive metabolism to the glucuronide relative to AZT. 935U83 showed low toxicity. In an in vitro assay for toxicity to a human erythrocyte progenitor, erythroid burst-forming unit (BFU-E), the IC50 for 935U83 (> 400 microM) was more than 1,000-fold those of FLT (0.07 microM) and AZT (0.30 microM). Mild reversible reductions in erythrocytes and associated parameters were seen in mice dosed orally with 2,000 mg of 935U83 per kg per day for 1 and 6 months. In monkeys dosed orally with up to 700 mg/kg/day for 1 and 6 months, the only possible treatment-related finding was cataracts in 1 of 12 animals given the intermediate dose of 225 mg/kg/day. At the highest doses in mice and monkeys, maximal concentrations in plasma were more than 100-fold the anti-HIV IC50s against clinical isolates. This safety profile in animals compares very favorably with that of any of the anti-HIV drugs approved to date and has led us to begin evaluation of 935U83 in patients with HIV infection. PMID:7526782

  15. Structure and Mechanistic Analysis of the Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5 in Complex with Its gp41 Epitope

    PubMed Central

    Ofek, Gilad; Tang, Min; Sambor, Anna; Katinger, Hermann; Mascola, John R.; Wyatt, Richard; Kwong, Peter D.

    2004-01-01

    The membrane-proximal region of the ectodomain of the gp41 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) is the target of three of the five broadly neutralizing anti-HIV-1 antibodies thus far isolated. We have determined crystal structures of the antigen-binding fragment for one of these antibodies, 2F5, in complex with 7-mer, 11-mer, and 17-mer peptides of the gp41 membrane-proximal region, at 2.0-, 2.1-, and 2.2-Å resolutions, respectively. The structures reveal an extended gp41 conformation, which stretches over 30 Å in length. Contacts are made with five complementarity-determining regions of the antibody as well as with nonpolymorphic regions. Only one exclusive charged face of the gp41 epitope is bound by 2F5, while the nonbound face, which is hydrophobic, may be hidden due to occlusion by other portions of the ectodomain. The structures reveal that the 2F5 antibody is uniquely built to bind to an epitope that is proximal to a membrane surface and in a manner mostly unaffected by large-scale steric hindrance. Biochemical studies with proteoliposomes confirm the importance of lipid membrane and hydrophobic context in the binding of 2F5 as well as in the binding of 4E10, another broadly neutralizing antibody that recognizes the membrane-proximal region of gp41. Based on these structural and biochemical results, immunization strategies for eliciting 2F5- and 4E10-like broadly neutralizing anti-HIV-1 antibodies are proposed. PMID:15367639

  16. A molecularly cloned, pathogenic, neutralization-resistant simian immunodeficiency virus, SIVsmE543-3.

    PubMed Central

    Hirsch, V; Adger-Johnson, D; Campbell, B; Goldstein, S; Brown, C; Elkins, W R; Montefiori, D C

    1997-01-01

    An infectious molecular clone of simian immunodeficiency virus SIVsm was derived from a biological isolate obtained late in disease from an immunodeficient rhesus macaque (E543) with SIV-induced encephalitis. The molecularly cloned virus, SIVsmE543-3, replicated well in macaque peripheral blood mononuclear cells and monocyte-derived macrophages and resisted neutralization by heterologous sera which broadly neutralized genetically diverse SIV variants in vitro. SIVsmE543-3 was infectious and induced AIDS when inoculated intravenously into pig-tailed macaques (Macaca nemestrina). Two of four infected macaques developed no measurable SIV-specific antibody and succumbed to a wasting syndrome and SIV-induced meningoencephalitis by 14 and 33 weeks postinfection. The other two macaques developed antibodies reactive in Western blot and virus neutralization assays. One macaque was sacrificed at 1 year postinoculation, and the survivor has evidence of immunodeficiency, characterized by persistently low CD4 lymphocyte subsets in the peripheral blood. Plasma samples from these latter animals neutralized SIVsmE543-3 but with much lower efficiency than neutralization of other related SIV strains, confirming the difficulty by which this molecularly cloned virus is neutralized in vitro. SIVsmE543-3 will provide a valuable reagent for studying SIV-induced encephalitis, mapping determinants of neutralization, and determining the in vivo significance of resistance to neutralization in vitro. PMID:8995688

  17. Crystal Structure and Structural Mechanism of a Novel Anti-Human Immunodeficiency Virus and D-Amino AcidContaining Chemokine

    Microsoft Academic Search

    Dongxiang Liu; Navid Madani; Ying Li; Rong Cao; Won-Tak Choi; Sameer P. Kawatkar; Mi Youn Lim; Santosh Kumar; Chang-Zhi Dong; Jun Wang; Julie D. Russell; Caroline R. Lefebure; Jing An; Scott Wilson; Yi-Gui Gao; Luke A. Pallansch; Joseph G. Sodroski; Ziwei Huang

    2007-01-01

    Chemokines and their receptors play important roles in normal physiological functions and the pathogeneses of a wide range of human diseases, including the entry of human immunodeficiency virus type 1 (HIV-1). However, the use of natural chemokines to probe receptor biology or to develop therapeutic drugs is limited by their lack of selectivity and the poor understanding of mechanisms in

  18. Anti-Human Immunodeficiency Virus Type 1 Microbicide Cellulose Acetate 1,2-Benzenedicarboxylate in a Human In Vitro Model of Vaginal Inflammation

    Microsoft Academic Search

    R. N. Fichorova; F. Zhou; V. Ratnam; V. Atanassova; S. Jiang; N. Strick; A. R. Neurath

    2005-01-01

    The sexual transmission of human immunodeficiency virus type 1 (HIV-1) is facilitated by inflammation and related epithelial barrier perturbation. Microbicides for vaginal applications are currently being developed to reduce the risk of HIV-1 transmission. However, little is known about their interference with epithelial immune function. In recent clinical trials, nonoxynol-9 (N-9), a virucide with a long history of intravaginal use

  19. Multicenter Evaluation of New Double-Antigen Sandwich Enzyme Immunoassay for Measurement of Anti-Human Immunodeficiency Virus Type 1 and Type 2 Antibodies

    Microsoft Academic Search

    PHILIPPE BURGISSER; FRANCOIS SIMON; MARTIN WERNLI; THOMAS WUST; MARIE-FRANCOISE BEYA; ANDPHILIPPE C. FREI; Regionales Blutspendezentrum; Groupe Hospitalier; Bichat-Claude Bernard

    1996-01-01

    A new enzyme immunoassay (EIA), the Cobas Core Anti-HIV-1\\/HIV-2 EIA DAGS (also referred to as Roche DAGS), for the detection of antibodies to human immunodeficiency virus type 1 (HIV-1) and HIV-2 was evaluated in four centers. The assay is based on the double-antigen sandwich (DAGS) format, which enables the detection of all classes of antibodies. The antigens consist of recombinant

  20. Potent Synergistic Anti-Human Immunodeficiency Virus (HIV) Effects Using Combinations of the CCR5 Inhibitor Aplaviroc with Other Anti-HIV Drugs

    Microsoft Academic Search

    Hirotomo Nakata; Seth M. Steinberg; Yasuhiro Koh; Kenji Maeda; Yoshikazu Takaoka; Hirokazu Tamamura; Nobutaka Fujii; Hiroaki Mitsuya

    2008-01-01

    Aplaviroc (AVC), an experimental CCR5 inhibitor, potently blocks in vitro the infection of R5-tropic human immunodeficiency virus type 1 (R5-HIV-1) at subnanomolar 50% inhibitory concentrations. Although maraviroc is presently clinically available, further studies are required to determine the role of CCR5 inhibitors in combinations with other drugs. Here we determined anti-HIV-1 activity using combinations of AVC with various anti-HIV-1 agents,

  1. Use of standardized SCID-hu Thy/Liv mouse model for preclinical efficacy testing of anti-human immunodeficiency virus type 1 compounds.

    PubMed Central

    Rabin, L; Hincenbergs, M; Moreno, M B; Warren, S; Linquist, V; Datema, R; Charpiot, B; Seifert, J; Kaneshima, H; McCune, J M

    1996-01-01

    We have developed standardized procedures and practices for infection of SCID-hu Thy/Liv mice with human immunodeficiency virus type 1 for the prophylactic administration of antiviral compounds and for evaluation of the antiviral effect in vivo. Endpoint analyses included quantitation of viral load by intracellular p24 enzyme-linked immunosorbent assay, DNA PCR for the presence of proviral genomes, flow cytometry to measure the representation of CD4+ and CD8+ cells, and cocultivation for the isolation of virus. Efficacy tests in this model are demonstrated with the nucleoside analogs zidovudine and dideoxyinosine and with the nonnucleoside reverse transcriptase inhibitor nevirapine. This small-animal model should be particularly useful in the preclinical prioritization of lead compounds within a common chemical class, in the evaluation of alternative in vivo dosing regimens, and in the determination of appropriate combination therapy in vivo. PMID:8851606

  2. Three amino acid residues in the envelope of human immunodeficiency virus type 1 CRF07_BC regulate viral neutralization susceptibility to the human monoclonal neutralizing antibody IgG1b12.

    PubMed

    Nie, Jianhui; Zhao, Juan; Chen, Qingqing; Huang, Weijin; Wang, Youchun

    2014-10-01

    The CD4 binding site (CD4bs) of envelope glycoprotein (Env) is an important conserved target for anti-human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies. Neutralizing monoclonal antibodies IgG1 b12 (b12) could recognize conformational epitopes that overlap the CD4bs of Env. Different virus strains, even derived from the same individual, showed distinct neutralization susceptibility to b12. We examined the key amino acid residues affecting b12 neutralization susceptibility using single genome amplification and pseudovirus neutralization assay. Eleven amino acid residues were identified that affect the sensitivity of Env to b12. Through site-directed mutagenesis, an amino acid substitution at position 182 in the V2 region of Env was confirmed to play a key role in regulating the b12 neutralization susceptibility. The introduction of V182L to a resistant strain enhanced its sensitivity to b12 more than twofold. Correspondingly, the introduction of L182V to a sensitive strain reduced its sensitivity to b12 more than tenfold. Amino acid substitution at positions 267 and 346 could both enhance the sensitivity to b12 more than twofold. However, no additive effect was observed when the three site mutageneses were introduced into the same strain, and the sensitivity was equivalent to the single V182L mutation. CRF07_BC is a major circulating recombinant form of HIV-1 prevalent in China. Our data may provide important information for understanding the molecular mechanism regulating the neutralization susceptibility of CRF07_BC viruses to b12 and may be helpful for a vaccine design targeting the CD4bs epitopes. PMID:25273335

  3. Antiviral efficacy in vivo of the anti-human immunodeficiency virus bicyclam SDZ SID 791 (JM 3100), an inhibitor of infectious cell entry.

    PubMed Central

    Datema, R; Rabin, L; Hincenbergs, M; Moreno, M B; Warren, S; Linquist, V; Rosenwirth, B; Seifert, J; McCune, J M

    1996-01-01

    SID 791, a bicyclam inhibiting human immunodeficiency virus (HIV) replication in vitro by blocking virus entry into cells, is an effective inhibitor of virus production and of depletion of human CD4+ T cells in HIV type 1-infected SCID-hu Thy/Liv mice. Steady levels of 100 ng of SID 791 or higher per ml in plasma resulted in statistically significant inhibition of p24 antigen formation. Daily injections of SID 791 caused a dose-dependent decrease in viremia, and this inhibition could be potentiated by coadministration of zidovudine or didanose. The present study suggests that SID 791 alone or in combination with licensed antiviral agents may decrease the virus load in HIV-infected patients and, by extension, that the infectious cell entry step is a valid target for antiviral chemotherapy of HIV disease. The SCID-hu Thy/Liv model in effect provides a rapid means of assessing the potential of compounds with novel modes of antiviral action, as well as the potential of antiviral drug combinations. PMID:8851605

  4. Anti-human immunodeficiency virus 1 (HIV-1) activities of 3-deazaadenosine analogs: increased potency against 3'-azido-3'-deoxythymidine-resistant HIV-1 strains.

    PubMed Central

    Mayers, D L; Mikovits, J A; Joshi, B; Hewlett, I K; Estrada, J S; Wolfe, A D; Garcia, G E; Doctor, B P; Burke, D S; Gordon, R K

    1995-01-01

    3-Deazaadenosine (DZA), 3-deaza-(+/-)-aristeromycin (DZAri), and 3-deazaneplanocin A (DZNep) are powerful modulators of cellular processes. When tested against H9 cells infected acutely with two different strains of human immunodeficiency virus 1 (HIV-1) and in the chronically infected monocytoid cell lines U1 and THP-1, the 3-deazanucleosides caused a marked reduction in p24 antigen production. Similar reductions in p24 antigen were seen in phytohemagglutinin-stimulated peripheral blood mononuclear cells infected with clinical HIV-1 isolates. Strikingly, in comparing the therapeutic indices between the paired pre- and post-3'-azido-3'-deoxythymidine (AZT) treatment HIV-1 isolates, DZNep and neplanocin A showed an increase of 3- to 18-fold in their potency against AZT-resistant HIV-1 isolates. In H9 cells treated with DZNep and DZAri, the formation of triphosphate nucleotides of DZNep and DZAri was observed. The mode of action of DZNep and DZAri appears complex, at least in part, at the level of infectivity as shown by decreases in syncytia formation in HIV-1-infected H9 cells and at the level of transcription as both drugs inhibited the expression of basal or tat-induced HIV-1 long terminal repeat chloramphenicol acetyltransferase activity in stably transfected cell lines. Since DZNep induced in H9 cells a rapid expression of nuclear binding factors that recognize the AP-1 transcription site, the anti-HIV-1 activity of the DZA analogs could partly be the induction of critical factors in the host cells. Thus, the 3-deazanucleoside drugs belong to an unusual class of anti-HIV-1 drugs, which may have therapeutic potential, in particular against AZT-resistant strains. Images Fig. 4 Fig. 5 PMID:7816820

  5. Cross-reactivity of anti-human immunodeficiency virus type 1 gp41 antibodies with human astrocytes and astrocytoma cell lines.

    PubMed Central

    Spehar, T; Strand, M

    1994-01-01

    An antigen expressed by astrocytes in human brain tissue and by various human astrocytoma cell lines was shown to cross-react with a monoclonal antibody generated against amino acids (aa) 584 to 609 of the transmembrane protein gp41 of human immunodeficiency virus type 1 (HIV-1). This region is an immunodominant segment of gp41, and high levels of antibodies against this epitope have been detected in both serum and cerebrospinal fluid of HIV-infected individuals at all stages of HIV infection. Immunohistochemistry with this monoclonal antibody demonstrated the presence of a cross-reactive antigen in human brain tissue, with an increased frequency and intensity of staining in HIV-positive individuals when compared with HIV-negative controls. By using a panel of HIV-positive and -negative sera, we show that antibodies in HIV-positive serum specifically bound to the surfaces of human astrocytoma cells. HIV-positive sera depleted of antibodies recognizing gp41 aa 584 to 609 showed a significant diminution in cell surface binding. Conversely, the serum antibodies that bound to and were eluted from the aa 584 to 609 peptide also bound to the astrocyte cell surface. To identify the target antigen, the immunoreactivity of three astrocytoma cell lines was examined. By immunoprecipitation of metabolically labeled cell lysates and Western blot (immunoblot) analysis, we identified a protein of approximately 100 kDa as the target antigen. Cross-reactive antibodies between HIV proteins and astrocyte epitopes, such as this 100-kDa protein and others previously reported, suggests that an autoimmune response against these target antigens may disrupt the normal functions of astrocytes. Images PMID:8083966

  6. Feline immunodeficiency virus (FIV) vaccine efficacy and FIV neutralizing antibodies

    PubMed Central

    Coleman, James K.; Pu, Ruiyu; Martin, Marcus M.; Noon-Song, Ezra N.; Zwijnenberg, Raphael; Yamamoto, Janet K.

    2013-01-01

    A HIV-1 tier system has been developed to categorize the various subtype viruses based on their sensitivity to vaccine-induced neutralizing antibodies (NAbs): tier 1 with greatest sensitivity, tier 2 being moderately sensitive, and tier 3 being the least sensitive to NAbs (Mascola et al., J Virol 2005; 79:10103-7). Here, we define an FIV tier system using two related FIV dual-subtype (A+D) vaccines: the commercially available inactivated infected-cell vaccine (Fel-O-Vax® FIV) and its prototype vaccine solely composed of inactivated whole viruses. Both vaccines afforded combined protection rates of 100% against subtype-A tier-1 FIVPet, 89% against subtype-B tier-3 FIVFC1, 61% against recombinant subtype-A/B tier-2 FIVBang, 62% against recombinant subtype-F?/C tier-3 FIVNZ1, and 40% against subtype-A tier-2 FIVUK8 in short-duration (37–41 weeks) studies. In long-duration (76–80 weeks) studies, the commercial vaccine afforded a combined protection rate of at least 46% against the tier-2 and tier-3 viruses. Notably, protection rates observed here are far better than recently reported HIV-1 vaccine trials (Sanou et al., The Open AIDS 2012; 6:246-60). Prototype vaccine protection against two tier-3 and one tier-2 viruses was more effective than commercial vaccine. Such protection did not correlate with the presence of vaccine-induced NAbs to challenge viruses. This is the first large-scale (228 laboratory cats) study characterizing short- and long-duration efficacies of dual-subtype FIV vaccines against heterologous subtype and recombinant viruses, as well as FIV tiers based on in vitro NAb analysis and in vivo passive-transfer studies. These studies demonstrate that not all vaccine protection is mediated by vaccine-induced NAbs. PMID:23800540

  7. Modeling Virus- and Antibody-Specific Factors to Predict Human Immunodeficiency Virus (HIV-1) Neutralization Efficiency

    PubMed Central

    Haim, Hillel; Salas, Ignacio; McGee, Kathleen; Eichelberger, Noah; Winter, Elizabeth; Pacheco, Beatriz; Sodroski, Joseph

    2013-01-01

    SUMMARY Efforts to prevent human immunodeficiency virus (HIV-1) infection would benefit from understanding the factors that govern virus neutralization by antibodies. We present a mechanistic model for HIV-1 neutralization that includes both virus and antibody parameters. Variations in epitope integrity on the viral envelope glycoprotein (Env) trimer and Env reactivity to bound antibody influence neutralization susceptibility. In addition, we define an antibody-specific parameter, the perturbation factor (PF), that describes the degree of conformational change in the Env trimer required for a given antibody to bind. Minimally perturbing (low-PF) antibodies can efficiently neutralize viruses with a broad range of Env reactivities due to fast on-rates and high affinity for Env. Highly perturbing (high-PF) antibodies inhibit only viruses with reactive (perturbation-sensitive) Envs, often through irreversible mechanisms. Accounting for these quantifiable viral and antibody-associated parameters helps to predict the observed profiles of HIV-1 neutralization by antibodies with a wide range of potencies. PMID:24237700

  8. Role of Human Immunodeficiency Virus Type 1 Envelope Structure in the Induction of Broadly Neutralizing Antibodies

    PubMed Central

    Benjelloun, F.; Lawrence, P.; Verrier, B.; Genin, C.

    2012-01-01

    Very soon after the discovery of neutralizing antibodies (NAbs) toward human immunodeficiency virus type 1 (HIV-1) infection, it became apparent that characterization of these NAbs would be an important step in finding a cure for or a vaccine to eradicate HIV-1. Since the initial description of broadly cross-clade NAbs naturally produced in HIV-1 patients, numerous studies have described new viral targets for these antibodies. More recently, studies concerning new groups of patients able to control their viremia, such as long-term nonprogressors (LTNPs) or elite controllers, have described the generation of numerous envelope-targeted NAbs. Recent studies have marked a new stage in research on NAbs with the description of antibodies obtained from a worldwide screening of HIV-positive patients. These studies have permitted the discovery of NAb families with great potential for both neutralization and neutralization breadth, such as PG, PGT, CH, and highly active agonistic anti-CD4 binding site antibodies (HAADs), of which VRC01 and its variants are members. These antibodies are able to neutralize more than 80% of circulating strains without any autoreactivity and can be rapidly integrated into clinical trials in order to test their protective potential. In this review, we will focus on new insights into HIV-1 envelope structure and their implications for the generation of potent NAbs. PMID:23015715

  9. Chimeric influenza virus induces neutralizing antibodies and cytotoxic T cells against human immunodeficiency virus type 1.

    PubMed Central

    Li, S; Polonis, V; Isobe, H; Zaghouani, H; Guinea, R; Moran, T; Bona, C; Palese, P

    1993-01-01

    Expression vectors based on DNA or plus-stranded RNA viruses are being developed as vaccine carriers directed against various pathogens. Less is known about the use of negative-stranded RNA viruses, whose genomes have been refractory to direct genetic manipulation. Using a recently described reverse genetics method, we investigated whether influenza virus is able to present antigenic structures from other infectious agents. We engineered a chimeric influenza virus which expresses a 12-amino-acid peptide derived from the V3 loop of gp120 of human immunodeficiency virus type 1 (HIV-1) MN. This peptide was inserted into the loop of antigenic site B of the influenza A/WSN/33 virus hemagglutinin (HA). The resulting chimeric virus was recognized by specific anti-V3 peptide antibodies and a human anti-gp120 monoclonal antibody in both hemagglutination inhibition and neutralization assays. Mice immunized with the chimeric influenza virus produced anti-HIV antibodies which were able to bind to synthetic V3 peptide, to precipitate gp120, and to neutralize MN virus in human T-cell culture system. In addition, the chimeric virus was also capable of inducing cytotoxic T cells which specifically recognize the HIV sequence. These results suggest that influenza virus can be used as an expression vector for inducing both B- and T-cell-mediated immunity against other infectious agents. Images PMID:7692083

  10. Immunodeficiencies

    PubMed Central

    Ballow, M; Notarangelo, L; Grimbacher, B; Cunningham-Rundles, C; Stein, M; Helbert, M; Gathmann, B; Kindle, G; Knight, A K; Ochs, H D; Sullivan, K; Franco, J L

    2009-01-01

    Primary immunodeficiencies (PIDs) are uncommon, chronic and severe disorders of the immune system in which patients cannot mount a sufficiently protective immune response, leading to an increased susceptibility to infections. The treatment of choice for PID patients with predominant antibody deficiency is intravenous immunoglobulin (Ig) replacement therapy. Despite major advances over the last 20 years in the molecular characterization of PIDs, many patients remain undiagnosed or are diagnosed too late, with severe consequences. Various strategies to ensure timely diagnosis of PIDs are in place, and novel approaches are being developed. In recent years, several patient registries have been established. Such registries shed light on the pathology and natural history of these varied disorders. Analyses of the registry data may also reveal which patients are likely to respond well to higher Ig infusion rates and may help to determine the optimal dosing of Ig products. Faster infusion rates may lead to improved convenience for patients and thus increase patient compliance, and may reduce nursing time and the need for hospital resources. Data from two recent studies suggest that Gamunex® and Privigen® are well tolerated at high infusion rates. Nevertheless, careful selection of patients for high infusion rates, based on co-morbid conditions and tolerance of the current infusion rate, is advisable. Based on the available data, intravenous Ig offers broad protection against encapsulated organisms. As vaccine trends change, careful monitoring of specific antibody levels in the general population, such as those against pneumococcal and meningococcal bacteria, should be implemented. PMID:19883420

  11. An investigation of the breadth of neutralizing antibody response in cats naturally infected with feline immunodeficiency virus.

    PubMed

    B?czkowski, Pawe? M; Logan, Nicola; McMonagle, Elizabeth; Litster, Annette; Willett, Brian J; Hosie, Margaret J

    2015-03-01

    Neutralizing antibodies (NAbs) are believed to comprise an essential component of the protective immune response induced by vaccines against feline immunodeficiency virus (FIV) and human immunodeficiency virus (HIV) infections. However, relatively little is known about the role of NAbs in controlling FIV infection and subsequent disease progression. Here, we present studies where we examined the neutralization of HIV-luciferase pseudotypes bearing homologous and heterologous FIV envelope proteins (n?=?278) by sequential plasma samples collected at 6 month intervals from naturally infected cats (n?=?38) over a period of 18 months. We evaluated the breadth of the NAb response against non-recombinant homologous and heterologous clade A and clade B viral variants, as well as recombinants, and assessed the results, testing for evidence of an association between the potency of the NAb response and the duration of infection, CD4(+) T lymphocyte numbers, health status and survival times of the infected cats. Neutralization profiles varied significantly between FIV-infected cats and strong autologous neutralization, assessed using luciferase-based in vitro assays, did not correlate with the clinical outcome. No association was observed between strong NAb responses and either improved health status or increased survival time of infected animals, implying that other protective mechanisms were likely to be involved. Similarly, no correlation was observed between the development of autologous NAbs and the duration of infection. Furthermore, cross-neutralizing antibodies were evident in only a small proportion (13?%) of cats. PMID:25395594

  12. Sequential Evolution and Escape from Neutralization of Simian Immunodeficiency Virus SIVsmE660 Clones in Rhesus Macaques

    PubMed Central

    Wu, Fan; Ourmanov, Ilnour; Kuwata, Takeo; Goeken, Robert; Brown, Charles R.; Buckler-White, Alicia; Iyengar, Ranjini; Plishka, Ronald; Aoki, Scott T.

    2012-01-01

    Simian immunodeficiency virus (SIV) infection of rhesus macaques has become an important surrogate model for evaluating HIV vaccine strategies. The extreme resistance to neutralizing antibody (NAb) of many commonly used strains, such as SIVmac251/239 and SIVsmE543-3, limits their potential relevance for evaluating the role of NAb in vaccine protection. In contrast, SIVsmE660 is an uncloned virus that appears to be more sensitive to neutralizing antibody. To evaluate the role of NAb in this model, we generated full-length neutralization-sensitive molecular clones of SIVsmE660 and evaluated two of these by intravenous inoculation of rhesus macaques. All animals became infected and maintained persistent viremia that was accompanied by a decline in memory CD4+ T cells in blood and bronchoalveolar lavage fluid. High titers of autologous NAb developed by 4 weeks postinoculation but were not associated with control of viremia, and neutralization escape variants were detected concurrently with the generation of NAb. Neutralization escape was associated with substitutions and insertion/deletion polymorphisms in the V1 and V4 domains of envelope. Analysis of representative variants revealed that escape variants also induced NAbs within a few weeks of their appearance in plasma, in a pattern that is reminiscent of the escape of human immunodeficiency virus type 1 (HIV-1) isolates in humans. Although early variants maintained a neutralization-sensitive phenotype, viruses obtained later in infection were significantly less sensitive to neutralization than the parental viruses. These results indicate that NAbs exert selective pressure that drives the evolution of the SIV envelope and that this model will be useful for evaluating the role of NAb in vaccine-mediated protection. PMID:22696650

  13. Inter- and intraclade neutralization of human immunodeficiency virus type 1: genetic clades do not correspond to neutralization serotypes but partially correspond to gp120 antigenic serotypes.

    PubMed Central

    Moore, J P; Cao, Y; Leu, J; Qin, L; Korber, B; Ho, D D

    1996-01-01

    We have studied genetic variation among clades A through E of human immunodeficiency virus type 1 (HIV-1) at the levels of antibody binding to gp120 molecules and virus neutralization. We are unable to identify neutralization serotypes that correspond to the genetic clades. Instead, we observe that inter- and intraclade neutralization of primary isolates by HIV-1-positive sera is generally weak and sporadic; some sera show a reasonable degree of neutralization breadth and potency whereas others are relatively sensitive to neutralization, but no consistent pattern was found. However, a few sera were able to neutralize across clades with significant potency, an observation which may have implications for the feasibility of a broadly effective HIV-1 vaccine involving humoral immunity. Serological assays measuring anti-gp120 antibody binding also failed to identify serotypes that correspond precisely to the genetic clades, but some indications of clade-specific binding were observed, notably with sera from clades B and E. A representative protein for each clade (A through E) was selected on the basis of its specificity, defined as high seroreactivity with sera from individuals infected with virus of that clade and lower reactivity with sera from individuals infected with viruses from other clades. The seroreactivity patterns against these five proteins could be used to predict the genotype of the infecting virus with moderate success. PMID:8523556

  14. Autologous and heterologous neutralizing antibody responses following initial seroconversion in human immunodeficiency virus type 1-infected individuals.

    PubMed Central

    Moog, C; Fleury, H J; Pellegrin, I; Kirn, A; Aubertin, A M

    1997-01-01

    In the course of human immunodeficiency virus type 1 (HIV-1) infection, patients develop a strong and persistent immune response characterized by the production of HIV-specific antibodies. The aim of our study was to analyze the appearance of autologous and heterologous neutralizing antibodies in the sera of HIV-infected individuals. For this purpose, primary strains have been isolated from 18 HIV-1-infected subjects prior to seroconversion (in one case) or within 1 to 8 months after seroconversion. Sera, collected at the same time as the virus was isolated and at various times after isolation, have been analyzed for their ability to neutralize the autologous primary strains isolated early after infection, heterologous primary isolates, and cell-line adapted strains. Our neutralization assay, which combines serial dilutions of virus and serial dilutions of sera, is based on the determination of the serum dilution at which a fixed reduction in virus titer (90%) occurs. We have shown that (i) we could not detect autologous neutralizing antibodies in sera collected at the same time as we isolated viruses; (ii) we detected neutralizing antibodies against the autologous strains about 1 year after seroconversion, occasionally after 8 months, but sera were not always available to exclude the presence of neutralizing antibodies at earlier times; (iii) after 1 year, the neutralization response was highly specific to virus present during the early phase of HIV infection; and (iv) heterologous neutralization of primary isolates was detected later (after about 2 years). These results reveal the enormous diversity of neutralization determinants on primary isolates as well as a temporal evolution of the humoral response generating cross-reactive neutralizing antibodies. PMID:9094648

  15. Neutralizing Monoclonal Antibodies Block Human Immunodeficiency Virus Type 1 Infection of Dendritic Cells and Transmission to T Cells

    PubMed Central

    Frankel, Sarah S.; Steinman, Ralph M.; Michael, Nelson L.; Kim, Silvia Ratto; Bhardwaj, Nina; Pope, Melissa; Louder, Mark K.; Ehrenberg, Philip K.; Parren, Paul W. H. I.; Burton, Dennis R.; Katinger, Hermann; VanCott, Thomas C.; Robb, Merlin L.; Birx, Deborah L.; Mascola, John R.

    1998-01-01

    Prevention of the initial infection of mucosal dendritic cells (DC) and interruption of the subsequent transmission of HIV-1 from DC to T cells are likely to be important attributes of an effective human immunodeficiency virus type 1 (HIV-1) vaccine. While anti-HIV-1 neutralizing antibodies have been difficult to elicit by immunization, there are several human monoclonal antibodies (MAbs) that effectively neutralize virus infection of activated T cells. We investigated the ability of three well-characterized neutralizing MAbs (IgG1b12, 2F5, and 2G12) to block HIV-1 infection of human DC. DC were generated from CD14+ blood cells or obtained from cadaveric human skin. The MAbs prevented viral entry into purified DC and the ensuing productive infection in DC/T-cell cultures. When DC were first pulsed with HIV-1, MAbs blocked the subsequent transmission to unstimulated CD3+ T cells. Thus, neutralizing antibodies can block HIV-1 infection of DC and the cell-to-cell transmission of virus from infected DC to T cells. These data suggest that neutralizing antibodies could interrupt the initial events associated with mucosal transmission and regional spread of HIV-1. PMID:9811714

  16. Neutralizing Capacity of Monoclonal Antibodies That Recognize Peptide Sequences Underlying the Carbohydrates on gp41 of Simian Immunodeficiency Virus

    PubMed Central

    Martinez-Navio, José M.

    2012-01-01

    Extensive glycosylation of the envelope spikes of human and simian immunodeficiency virus (HIV and SIV) is an important factor for the resistance of these viruses to neutralization by antibodies. SIVmac239 gp41 has three closely spaced sites for N-linked carbohydrate attachment. Rhesus macaques experimentally infected with mutant versions of SIVmac239 lacking two or three of these carbohydrate sites developed strong serum reactivity against mutated peptide sequences at the site of these glycosylations, as well as high titers of neutralizing activity to the mutant viruses (E. Yuste et al., J. Virol. 82:12472–12486, 2008). However, whether antibodies that recognize these underlying peptides have neutralizing activity has not been directly demonstrated. Here we describe the isolation and characterization of three gp41-specific monoclonal antibodies (4G8, 6G8, and 7D6) from one of these mutant-infected monkeys. All three antibodies reacted with mutant gp41 from viral particles and also with peptides corresponding to mutated sequences. Slight differences in peptide specificities were observed among the three antibodies. Sequence analysis revealed that the heavy chains of all three antibodies were derived from the same germ line heavy-chain segment (IGHV4-59*01), but they all had very different sequences in complementarity-determining region 3. The light chains of all three antibodies were very closely related to one another. All three antibodies had neutralizing activity to mutant viruses deficient in gp41 carbohydrate attachment, but they did not neutralize the parental SIVmac239. These results demonstrate unambiguously that antibodies with specificity for peptide sequences underlying gp41 carbohydrates can effectively neutralize SIV when these carbohydrates are absent. However, the presence of these gp41 carbohydrates effectively shields the virus from antibodies that would otherwise neutralize viral infectivity. PMID:22993152

  17. Heterogeneity in Neutralization Sensitivities of Viruses Comprising the Simian Immunodeficiency Virus SIVsmE660 Isolate and Vaccine Challenge Stock

    PubMed Central

    Lopker, Michael; Easlick, Juliet; Sterrett, Sarah; Decker, Julie M.; Barbian, Hannah; Learn, Gerald; Keele, Brandon F.; Robinson, James E.; Li, Hui; Hahn, Beatrice H.; Shaw, George M.

    2013-01-01

    The sooty mangabey-derived simian immunodeficiency virus (SIV) strain E660 (SIVsmE660) is a genetically heterogeneous, pathogenic isolate that is commonly used as a vaccine challenge strain in the nonhuman primate (NHP) model of human immunodeficiency virus type 1 (HIV-1) infection. Though it is often employed to assess antibody-based vaccine strategies, its sensitivity to antibody-mediated neutralization has not been well characterized. Here, we utilize single-genome sequencing and infectivity assays to analyze the neutralization sensitivity of the uncloned SIVsmE660 isolate, individual viruses comprising the isolate, and transmitted/founder (T/F) viruses arising from low-dose mucosal inoculation of macaques with the isolate. We found that the SIVsmE660 isolate overall was highly sensitive to neutralization by SIV-infected macaque plasma samples (50% inhibitory concentration [IC50] < 10?5) and monoclonal antibodies targeting V3 (IC50 < 0.01 ?g/ml), CD4-induced (IC50 < 0.1 ?g/ml), CD4 binding site (IC50 ? 1 ?g/ml), and V4 (IC50, ?5 ?g/ml) epitopes. In comparison, SIVmac251 and SIVmac239 were highly resistant to neutralization by these same antibodies. Differences in neutralization sensitivity between SIVsmE660 and SIVmac251/239 were not dependent on the cell type in which virus was produced or tested. These findings indicate that in comparison to SIVmac251/239 and primary HIV-1 viruses, SIVsmE660 generally exhibits substantially less masking of antigenically conserved Env epitopes. Interestingly, we identified a minor population of viruses (?10%) in both the SIVsmE660 isolate and T/F viruses arising from it that were substantially more resistant (>1,000-fold) to antibody neutralization and another fraction (?20%) that was intermediate in neutralization resistance. These findings may explain the variable natural history and variable protection afforded by heterologous Env-based vaccines in rhesus macaques challenged by high-dose versus low-dose SIVsmE660 inoculation regimens. PMID:23468494

  18. Heterogeneity in neutralization sensitivities of viruses comprising the simian immunodeficiency virus SIVsmE660 isolate and vaccine challenge stock.

    PubMed

    Lopker, Michael; Easlick, Juliet; Sterrett, Sarah; Decker, Julie M; Barbian, Hannah; Learn, Gerald; Keele, Brandon F; Robinson, James E; Li, Hui; Hahn, Beatrice H; Shaw, George M; Bar, Katharine J

    2013-05-01

    The sooty mangabey-derived simian immunodeficiency virus (SIV) strain E660 (SIVsmE660) is a genetically heterogeneous, pathogenic isolate that is commonly used as a vaccine challenge strain in the nonhuman primate (NHP) model of human immunodeficiency virus type 1 (HIV-1) infection. Though it is often employed to assess antibody-based vaccine strategies, its sensitivity to antibody-mediated neutralization has not been well characterized. Here, we utilize single-genome sequencing and infectivity assays to analyze the neutralization sensitivity of the uncloned SIVsmE660 isolate, individual viruses comprising the isolate, and transmitted/founder (T/F) viruses arising from low-dose mucosal inoculation of macaques with the isolate. We found that the SIVsmE660 isolate overall was highly sensitive to neutralization by SIV-infected macaque plasma samples (50% inhibitory concentration [IC50] < 10(-5)) and monoclonal antibodies targeting V3 (IC50 < 0.01 ?g/ml), CD4-induced (IC50 < 0.1 ?g/ml), CD4 binding site (IC50 ~ 1 ?g/ml), and V4 (IC50, ~5 ?g/ml) epitopes. In comparison, SIVmac251 and SIVmac239 were highly resistant to neutralization by these same antibodies. Differences in neutralization sensitivity between SIVsmE660 and SIVmac251/239 were not dependent on the cell type in which virus was produced or tested. These findings indicate that in comparison to SIVmac251/239 and primary HIV-1 viruses, SIVsmE660 generally exhibits substantially less masking of antigenically conserved Env epitopes. Interestingly, we identified a minor population of viruses (~10%) in both the SIVsmE660 isolate and T/F viruses arising from it that were substantially more resistant (>1,000-fold) to antibody neutralization and another fraction (~20%) that was intermediate in neutralization resistance. These findings may explain the variable natural history and variable protection afforded by heterologous Env-based vaccines in rhesus macaques challenged by high-dose versus low-dose SIVsmE660 inoculation regimens. PMID:23468494

  19. Anti-human immunodeficiency virus activity of a novel synthetic peptide, T22 ([Tyr-5,12, Lys-7]polyphemusin II): a possible inhibitor of virus-cell fusion.

    PubMed Central

    Nakashima, H; Masuda, M; Murakami, T; Koyanagi, Y; Matsumoto, A; Fujii, N; Yamamoto, N

    1992-01-01

    More than 40 peptides associated with tachyplesin and polyphemusin, which are highly abundant in hemocyte debris of the horseshoe crabs Tachypleus tridentatus and Limulus polyphemus, were synthesized. Among these peptides, we found that a novel compound, which was called T22 ([Tyr-5,12, Lys-7]polyphemusin II), strongly inhibited the human immunodeficiency virus type 1 (HIV-1)-induced cytopathic effect and viral antigen expression. Its 50% effective concentration was 0.008 micrograms/ml, while its 50% cytotoxic concentration was 54 micrograms/ml. The anti-HIV activity of T22 was observed with several strains of HIV-1, including zidovudine-resistant strains, and with HIV-2 within the concentration range of 0.006 to 0.071 microgram/ml. T22 efficiently inhibited giant cell formation on the cocultivation of MOLT-4/HIV and MOLT-4 cells but modestly inhibited direct HIV binding. T22 did not inhibit reverse transcriptase activity. A time-of-addition study, which involved monitoring of the appearance of proviral DNA by using the polymerase chain reaction technique, found that T22 exerted its effect on a process, most probably virus-cell fusion or uncoating, immediately after virus adsorption. Images PMID:1384424

  20. Human Immunodeficiency Virus Type 1 env Clones from Acute and Early Subtype B Infections for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies

    Microsoft Academic Search

    Ming Li; Feng Gao; John R. Mascola; Leonidas Stamatatos; Victoria R. Polonis; Marguerite Koutsoukos; Gerald Voss; Paul Goepfert; Peter Gilbert; Kelli M. Greene; Miroslawa Bilska; Denise L. Kothe; Jesus F. Salazar-Gonzalez; Xiping Wei; Julie M. Decker; Beatrice H. Hahn; David C. Montefiori

    2005-01-01

    Induction of broadly cross-reactive neutralizing antibodies is a high priority for AIDS vaccine development but one that has proven difficult to be achieved. While most immunogens generate antibodies that neutralize a subset of T-cell-line-adapted strains of human immunodeficiency virus type 1 (HIV-1), none so far have generated a potent, broadly cross-reactive response against primary isolates of the virus. Even small

  1. Structure-Function Analysis of the Epitope for 4E10, a Broadly Neutralizing Human Immunodeficiency Virus Type 1 Antibody†

    PubMed Central

    Brunel, Florence M.; Zwick, Michael B.; Cardoso, Rosa M. F.; Nelson, Josh D.; Wilson, Ian A.; Burton, Dennis R.; Dawson, Philip E.

    2006-01-01

    The human immunodeficiency virus type 1 (HIV-1) neutralizing antibody 4E10 binds to a linear, highly conserved epitope within the membrane-proximal external region of the HIV-1 envelope glycoprotein gp41. We have delineated the peptide epitope of the broadly neutralizing 4E10 antibody to gp41 residues 671 to 683, using peptides with different lengths encompassing the previously suggested core epitope (NWFDIT). Peptide binding to the 4E10 antibody was assessed by competition enzyme-linked immunosorbent assay, and the Kd values of selected peptides were determined using surface plasmon resonance. An Ala scan of the epitope indicated that several residues, W672, F673, and T676, are essential (>1,000-fold decrease in binding upon replacement with alanine) for 4E10 recognition. In addition, five other residues, N671, D674, I675, W680, and L679, make significant contributions to 4E10 binding. In general, the Ala scan results agree well with the recently reported crystal structure of 4E10 in complex with a 13-mer peptide and with our circular dichroism analyses. Neutralization competition assays confirmed that the peptide NWFDITNWLWYIKKKK-NH2 could effectively inhibit 4E10 neutralization. Finally, to limit the conformational flexibility of the peptides, helix-promoting 2-aminoisobutyric acid residues and helix-inducing tethers were incorporated. Several peptides have significantly improved affinity (>1,000-fold) over the starting peptide and, when used as immunogens, may be more likely to elicit 4E10-like neutralizing antibodies. Hence, this study represents the first stage toward iterative development of a vaccine based on the 4E10 epitope. PMID:16439525

  2. Structure-function analysis of the epitope for 4E10, a broadly neutralizing human immunodeficiency virus type 1 antibody.

    PubMed

    Brunel, Florence M; Zwick, Michael B; Cardoso, Rosa M F; Nelson, Josh D; Wilson, Ian A; Burton, Dennis R; Dawson, Philip E

    2006-02-01

    The human immunodeficiency virus type 1 (HIV-1) neutralizing antibody 4E10 binds to a linear, highly conserved epitope within the membrane-proximal external region of the HIV-1 envelope glycoprotein gp41. We have delineated the peptide epitope of the broadly neutralizing 4E10 antibody to gp41 residues 671 to 683, using peptides with different lengths encompassing the previously suggested core epitope (NWFDIT). Peptide binding to the 4E10 antibody was assessed by competition enzyme-linked immunosorbent assay, and the K(d) values of selected peptides were determined using surface plasmon resonance. An Ala scan of the epitope indicated that several residues, W672, F673, and T676, are essential (>1,000-fold decrease in binding upon replacement with alanine) for 4E10 recognition. In addition, five other residues, N671, D674, I675, W680, and L679, make significant contributions to 4E10 binding. In general, the Ala scan results agree well with the recently reported crystal structure of 4E10 in complex with a 13-mer peptide and with our circular dichroism analyses. Neutralization competition assays confirmed that the peptide NWFDITNWLWYIKKKK-NH(2) could effectively inhibit 4E10 neutralization. Finally, to limit the conformational flexibility of the peptides, helix-promoting 2-aminoisobutyric acid residues and helix-inducing tethers were incorporated. Several peptides have significantly improved affinity (>1,000-fold) over the starting peptide and, when used as immunogens, may be more likely to elicit 4E10-like neutralizing antibodies. Hence, this study represents the first stage toward iterative development of a vaccine based on the 4E10 epitope. PMID:16439525

  3. Proline-rich tandem repeats of antibody complementarity-determining regions bind and neutralize human immunodeficiency virus type 1 particles.

    PubMed Central

    Fontenot, J D; Zacharopoulos, V R; Phillips, D M

    1996-01-01

    The proline-rich tandem repeat domain of human mucin MUC1 forms an extended structure containing large repeating loops that are crested by a turn. We show that the repeating-loop structure of MUC1 can be replaced by an antibody complementarity-determining region loop of a human immunodeficiency virus type 1 (HIV-1)-specific neutralizing antibody to create a chimeric, multivalent, mucin-like, anti-HIV-1 compound. We used 8 residues of an antibody molecule to replace 8 of 20 residues of the MUC1 tandem-repeat sequence. The antiviral peptide discussed here contains three copies of a 20-residue tandem repeat, (IYYDYEEDPAPGSTAPPAHG)3, for a total of 60 residues. We demonstrate that the mucin-antibody chimera retains the binding specificity of the parent antibody (monoclonal antibody F58), GPGR of the HIV-1 gp120 V3 neutralizing epitope, and the ability to neutralize virus particles. In inhibition enzyme-linked immunosorbent assay, the mucin-antibody chimeric peptide could inhibit 71 to 84% of binding to a V3 loop peptide by monoclonal antibodies known to be specific for GPGR in the V3 loop. The mucin-antibody chimeric peptide could also inhibit monoclonal antibody binding to native gp120 captured from virus particles. In addition, the chimeric peptide neutralized the homologous HIV-IIIB virus in a standard neutralization assay. The methods of antiviral peptide design and construction presented here are general and theoretically limited only by the size of the antibody repertoire. This approach could be used to synthesize peptides for a variety of therapeutic applications. PMID:8794290

  4. Neutralizing IgG at the Portal of Infection Mediates Protection against Vaginal Simian/Human Immunodeficiency Virus Challenge

    PubMed Central

    Klein, Katja; Veazey, Ronald S.; Warrier, Ranjit; Hraber, Peter; Doyle-Meyers, Lara A.; Buffa, Viviana; Liao, Hua-Xin; Haynes, Barton F.; Shaw, George M.

    2013-01-01

    Neutralizing antibodies may have critical importance in immunity against human immunodeficiency virus type 1 (HIV-1) infection. However, the amount of protective antibody needed at mucosal surfaces has not been fully established. Here, we evaluated systemic and mucosal pharmacokinetics (PK) and pharmacodynamics (PD) of 2F5 IgG and 2F5 Fab fragments with respect to protection against vaginal challenge with simian-human immunodeficiency virus-BaL in macaques. Antibody assessment demonstrated that 2F5 IgG was more potent than polymeric forms (IgM and IgA) across a range of cellular and tissue models. Vaginal challenge studies demonstrated a dose-dependent protection for 2F5 IgG and no protection with 2F5 Fab despite higher vaginal Fab levels at the time of challenge. Animals receiving 50 or 25 mg/kg of body weight 2F5 IgG were completely protected, while 3/5 animals receiving 5 mg/kg were protected. In the control animals, infection was established by a minimum of 1 to 4 transmitted/founder (T/F) variants, similar to natural human infection by this mucosal route; in the two infected animals that had received 5 mg 2F5 IgG, infection was established by a single T/F variant. Serum levels of 2F5 IgG were more predictive of sterilizing protection than measured vaginal levels. Fc-mediated antiviral activity did not appear to influence infection of primary target cells in cervical explants. However, PK studies highlighted the importance of the Fc portion in tissue biodistribution. Data presented in this study may be important in modeling serum levels of neutralizing antibodies that need to be achieved by either vaccination or passive infusion to prevent mucosal acquisition of HIV-1 infection in humans. PMID:23966410

  5. Potent Intratype Neutralizing Activity Distinguishes Human Immunodeficiency Virus Type 2 (HIV-2) from HIV-1

    PubMed Central

    Özkaya ?ahin, Gül?en; Holmgren, Birgitta; da Silva, Zacarias; Nielsen, Jens; Nowroozalizadeh, Salma; Esbjörnsson, Joakim; Månsson, Fredrik; Andersson, Sören; Norrgren, Hans; Aaby, Peter

    2012-01-01

    HIV-2 has a lower pathogenicity and transmission rate than HIV-1. Neutralizing antibodies could be contributing to these observations. Here we explored side by side the potency and breadth of intratype and intertype neutralizing activity (NAc) in plasma of 20 HIV-1-, 20 HIV-2-, and 11 dually HIV-1/2 (HIV-D)-seropositive individuals from Guinea-Bissau, West Africa. Panels of primary isolates, five HIV-1 and five HIV-2 isolates, were tested in a plaque reduction assay using U87.CD4-CCR5 cells as targets. Intratype NAc in HIV-2 plasma was found to be considerably more potent and also broader than intratype NAc in HIV-1 plasma. This indicates that HIV-2-infected individuals display potent type-specific neutralizing antibodies, whereas such strong type-specific antibodies are absent in HIV-1 infection. Furthermore, the potency of intratype NAc was positively associated with the viral load of HIV-1 but not HIV-2, suggesting that NAc in HIV-1 infection is more antigen stimulation dependent than in HIV-2 infection, where plasma viral loads typically are at least 10-fold lower than in HIV-1 infection. Intertype NAc of both HIV-1 and HIV-2 infections was, instead, of low potency. HIV-D subjects had NAc to HIV-2 with similar high potency as singly HIV-2-infected individuals, whereas neutralization of HIV-1 remained poor, indicating that the difference in NAc between HIV-1 and HIV-2 infections depends on the virus itself. We suggest that immunogenicity and/or antigenicity, meaning the neutralization phenotype, of HIV-2 is distinct from that of HIV-1 and that HIV-2 may display structures that favor triggering of potent neutralizing antibody responses. PMID:22072782

  6. Interactions between Natural Killer Cells and Antibody Fc Result in Enhanced Antibody Neutralization of Human Immunodeficiency Virus Type 1

    PubMed Central

    Forthal, Donald N.; Landucci, Gary; Phan, Tran B.; Becerra, Juan

    2005-01-01

    Antibodies can prevent lentivirus infections in animals and may play a role in controlling viral burden in established infection. In preventing and particularly in controlling infection, antibodies likely function in the presence of large quantities of virus. In this study, we explored the mechanisms by which antibodies neutralize large inocula of human immunodeficiency virus type 1 (HIV-1) on different target cells. Immunoglobulin G (IgG) from HIV-infected patients was tested for neutralizing activity against primary R5 strains of HIV-1 at inocula ranging from 100 to 20,000 50% tissue culture infective doses. At all virus inocula, inhibition by antibody was enhanced when target cells for virus growth were monocyte-depleted, peripheral blood mononuclear cells (PBMCs) rather than CD4+ lymphocytes. However, enhanced inhibition on PBMCs was greatest with larger amounts of virus. Depleting PBMCs of natural killer (NK) cells, which express Fc receptors for IgG (Fc?Rs), abrogated the enhanced antibody inhibition, whereas adding NK cells to CD4+ lymphocytes restored inhibition. There was no enhanced inhibition on PBMCs when F(ab?)2 was used. Further experiments demonstrated that the release of ?-chemokines, most likely through Fc?R triggering of NK cells, contributed modestly to the antiviral activity of antibody on PBMCs and that antibody-coated virus adsorbed to uninfected cells provided a target for NK cell-mediated inhibition of HIV-1. These results indicate that Fc-Fc?R interactions enhance the ability of antibody to neutralize HIV-1. Since Fc?R-bearing cells are always present in vivo, Fc?R-mediated antibody function may play a role in the ability of antibody to control lentivirus infection. PMID:15681406

  7. Impact of amino acid substitutions in the V2 and C2 regions of human immunodeficiency virus type 1 CRF01_AE envelope glycoprotein gp120 on viral neutralization susceptibility to broadly neutralizing antibodies specific for the CD4 binding site

    PubMed Central

    2014-01-01

    Background The CD4 binding site (CD4bs) of envelope glycoprotein (Env) gp120 is a functionally conserved, important target of anti-human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies. Two neutralizing human monoclonal antibodies, IgG1 b12 (b12) and VRC01, are broadly reactive neutralizing antibodies which recognize conformational epitopes that overlap the CD4bs of Env gp120; however, many CRF01_AE viruses are resistant to neutralization mediated by these antibodies. We examined the mechanism underlying the b12 resistance of the viruses using CRF01_AE Env (AE-Env)-recombinant viruses in this study. Results Our results showed that an amino acid substitution at position 185 in the V2 region of gp120 played a crucial role in regulating the b12 susceptibility of AE-Env-recombinant viruses by cooperating with 2 previously reported potential N-linked glycosylation (PNLG) sites at positions 186 (N186) and 197 (N197) in the V2 and C2 regions of Env gp120. The amino acid residue at position 185 and 2 PNLG sites were responsible for the b12 resistance of 21 of 23 (>91%) AE-Env clones tested. Namely, the introduction of aspartic acid at position 185 (D185) conferred b12 susceptibility of 12 resistant AE-Env clones in the absence of N186 and/or N197, while the introduction of glycine at position 185 (G185) reduced the b12 susceptibility of 9 susceptible AE-Env clones in the absence of N186 and/or N197. In addition, these amino acid mutations altered the VRC01 susceptibility of many AE-Env clones. Conclusions We propose that the V2 and C2 regions of AE-Env gp120 contain the major determinants of viral resistance to CD4bs antibodies. CRF01_AE is a major circulating recombinant form of HIV-1 prevalent in Southeast Asia. Our data may provide important information to understand the molecular mechanism regulating the neutralization susceptibility of CRF01_AE viruses to CD4bs antibodies. PMID:24758333

  8. Antibodies with Specificity to Native gp120 and Neutralization Activity against Primary Human Immunodeficiency Virus Type 1 Isolates Elicited by Immunization with Oligomeric gp160

    Microsoft Academic Search

    THOMAS C. VANCOTT; J. R. MASCOLA; R. W. KAMINSKI; V. KALYANARAMAN; P. L. HALLBERG; P. R. BURNETT; J. T. ULRICH; D. J. RECHTMAN; D. L. BIRX; Henry M. Jackson; Ribi ImmunoChem

    1997-01-01

    Current human immunodeficiency virus type 1 (HIV-1) envelope vaccine candidates elicit high antibody binding titers with neutralizing activity against T-cell line-adapted but not primary HIV-1 isolates. Serum antibodies from these human vaccine recipients were also found to be preferentially directed to linear epitopes within gp120 that are poorly exposed on native gp120. Systemic immunization of rabbits with an affinity- purified

  9. Role of Complex Carbohydrates in Human Immunodeficiency Virus Type 1 Infection and Resistance to Antibody Neutralization?

    PubMed Central

    Binley, James M.; Ban, Yih-En Andrew; Crooks, Emma T.; Eggink, Dirk; Osawa, Keiko; Schief, William R.; Sanders, Rogier W.

    2010-01-01

    Complex N-glycans flank the receptor binding sites of the outer domain of HIV-1 gp120, ostensibly forming a protective “fence” against antibodies. Here, we investigated the effects of rebuilding this fence with smaller glycoforms by expressing HIV-1 pseudovirions from a primary isolate in a human cell line lacking N-acetylglucosamine transferase I (GnTI), the enzyme that initiates the conversion of oligomannose N-glycans into complex N-glycans. Thus, complex glycans, including those that surround the receptor binding sites, are replaced by fully trimmed oligomannose stumps. Conversely, the untrimmed oligomannoses of the silent domain of gp120 are likely to remain unchanged. For comparison, we produced a mutant virus lacking a complex N-glycan of the V3 loop (N301Q). Both variants exhibited increased sensitivities to V3 loop-specific monoclonal antibodies (MAbs) and soluble CD4. The N301Q virus was also sensitive to “nonneutralizing” MAbs targeting the primary and secondary receptor binding sites. Endoglycosidase H treatment resulted in the removal of outer domain glycans from the GnTI- but not the parent Env trimers, and this was associated with a rapid and complete loss in infectivity. Nevertheless, the glycan-depleted trimers could still bind to soluble receptor and coreceptor analogs, suggesting a block in post-receptor binding conformational changes necessary for fusion. Collectively, our data show that the antennae of complex N-glycans serve to protect the V3 loop and CD4 binding site, while N-glycan stems regulate native trimer conformation, such that their removal can lead to global changes in neutralization sensitivity and, in extreme cases, an inability to complete the conformational rearrangements necessary for infection. PMID:20335257

  10. Role of complex carbohydrates in human immunodeficiency virus type 1 infection and resistance to antibody neutralization.

    PubMed

    Binley, James M; Ban, Yih-En Andrew; Crooks, Emma T; Eggink, Dirk; Osawa, Keiko; Schief, William R; Sanders, Rogier W

    2010-06-01

    Complex N-glycans flank the receptor binding sites of the outer domain of HIV-1 gp120, ostensibly forming a protective "fence" against antibodies. Here, we investigated the effects of rebuilding this fence with smaller glycoforms by expressing HIV-1 pseudovirions from a primary isolate in a human cell line lacking N-acetylglucosamine transferase I (GnTI), the enzyme that initiates the conversion of oligomannose N-glycans into complex N-glycans. Thus, complex glycans, including those that surround the receptor binding sites, are replaced by fully trimmed oligomannose stumps. Conversely, the untrimmed oligomannoses of the silent domain of gp120 are likely to remain unchanged. For comparison, we produced a mutant virus lacking a complex N-glycan of the V3 loop (N301Q). Both variants exhibited increased sensitivities to V3 loop-specific monoclonal antibodies (MAbs) and soluble CD4. The N301Q virus was also sensitive to "nonneutralizing" MAbs targeting the primary and secondary receptor binding sites. Endoglycosidase H treatment resulted in the removal of outer domain glycans from the GnTI- but not the parent Env trimers, and this was associated with a rapid and complete loss in infectivity. Nevertheless, the glycan-depleted trimers could still bind to soluble receptor and coreceptor analogs, suggesting a block in post-receptor binding conformational changes necessary for fusion. Collectively, our data show that the antennae of complex N-glycans serve to protect the V3 loop and CD4 binding site, while N-glycan stems regulate native trimer conformation, such that their removal can lead to global changes in neutralization sensitivity and, in extreme cases, an inability to complete the conformational rearrangements necessary for infection. PMID:20335257

  11. CD40L-Adjuvanted DNA/Modified Vaccinia Virus Ankara Simian Immunodeficiency Virus (SIV) Vaccine Enhances Protection against Neutralization-Resistant Mucosal SIV Infection.

    PubMed

    Kwa, Suefen; Sadagopal, Shanmugalakshmi; Shen, Xiaoying; Hong, Jung Joo; Gangadhara, Sailaja; Basu, Rahul; Victor, Blandine; Iyer, Smita S; LaBranche, Celia C; Montefiori, David C; Tomaras, Georgia D; Villinger, Francois; Moss, Bernard; Kozlowski, Pamela A; Amara, Rama Rao

    2015-04-15

    Here, we show that a CD40L-adjuvanted DNA/modified vaccinia virus Ankara (MVA) simian immunodeficiency virus (SIV) vaccine enhances protection against a pathogenic neutralization-resistant mucosal SIV infection, improves long-term viral control, and prevents AIDS. Analyses of serum IgG antibodies to linear peptides of SIV Env revealed a strong response to V2, with targeting of fewer epitopes in the immunodominant region of gp41 (gp41-ID) and the V1 region as a correlate for enhanced protection. Greater expansion of antiviral CD8 T cells in the gut correlated with long-term viral control. PMID:25653428

  12. Autologous Neutralizing Humoral Immunity and Evolution of the Viral Envelope in the Course of Subtype B Human Immunodeficiency Virus Type 1 Infection ? †

    PubMed Central

    Bunnik, Evelien M.; Pisas, Linaida; van Nuenen, Ad C.; Schuitemaker, Hanneke

    2008-01-01

    Most human immunodeficiency virus type 1 (HIV-1)-infected individuals develop an HIV-specific neutralizing antibody (NAb) response that selects for escape variants of the virus. Here, we studied autologous NAb responses in five typical CCR5-using progressors in relation to viral NAb escape and molecular changes in the viral envelope (Env) in the period from seroconversion until after AIDS diagnosis. In sera from three patients, high-titer neutralizing activity was observed against the earliest autologous virus variants, followed by declining humoral immune responses against subsequent viral escape variants. Autologous neutralizing activity was undetectable in sera from two patients. Patients with high-titer neutralizing activity in serum showed the strongest positive selection pressure on Env early in infection. In the initial phase of infection, gp160 length and the number of potential N-linked glycosylation sites (PNGS) increased in viruses from all patients. Over the course of infection, positive selection pressure declined as the NAb response subsided, coinciding with reversions of changes in gp160 length and the number of PNGS. A number of identical amino acid changes were observed over the course of infection in the viral quasispecies of different patients. Our results indicate that although neutralizing autologous humoral immunity may have a limited effect on the disease course, it is an important selection pressure in virus evolution early in infection, while declining HIV-specific humoral immunity in later stages may coincide with reversion of NAb-driven changes in Env. PMID:18524815

  13. Replication and neutralization of human immunodeficiency virus type 1 lacking the V1 and V2 variable loops of the gp120 envelope glycoprotein.

    PubMed Central

    Cao, J; Sullivan, N; Desjardin, E; Parolin, C; Robinson, J; Wyatt, R; Sodroski, J

    1997-01-01

    A human immunodeficiency virus type 1 (HIV-1) mutant lacking the V1 and V2 variable loops in the gp120 exterior envelope glycoprotein replicated in Jurkat lymphocytes with only modest delays compared with the wild-type virus. Revertants that replicated with wild-type efficiency rapidly emerged and contained only a few amino acid changes in the envelope glycoproteins compared with the parent virus. Both the parent and revertant viruses exhibited increased sensitivity to neutralization by antibodies directed against the V3 loop or a CD4-induced epitope on gp120 but not by soluble CD4 or an antibody against the CD4 binding site. This result demonstrates the role of the gp120 V1 and V2 loops in protecting HIV-1 from some subsets of neutralizing antibodies. PMID:9371651

  14. Comparison of Neutralizing and Hemagglutination-Inhibiting Antibody Responses to Influenza A Virus Vaccination of Human Immunodeficiency Virus-Infected Individuals

    PubMed Central

    Benne, C. A.; Kroon, F. P.; Harmsen, M.; Tavares, L.; Kraaijeveld, C. A.; De Jong, J. C.

    1998-01-01

    A neutralization enzyme immunoassay (N-EIA) was used to determine the neutralizing serum antibody titers to influenza A/Taiwan/1/86 (H1N1) and Beijing/353/89 (H3N2) viruses after vaccination of 51 human immunodeficiency virus (HIV) type 1-infected individuals and 10 healthy noninfected controls against influenza virus infection. Overall, the N-EIA titers correlated well with the hemagglutination-inhibition (HAI) titers that were observed in the same samples in a previous study (F. P. Kroon, J. T. van Dissel, J. C. de Jong, and R. van Furth, AIDS 8:469–476,1994). The N-EIA appeared to be more sensitive than the HAI test. Significantly more fourfold or higher rises in N-EIA titer and higher mean N-EIA titers occurred in HIV-infected individuals with ?200 CD4+ cells per ?l than in those with <200 CD4+ cells per ?l. PMID:9455891

  15. The Membrane-Proximal External Region of the Human Immunodeficiency Virus Type 1 Envelope: Dominant Site of Antibody Neutralization and Target for Vaccine Design

    PubMed Central

    Montero, Marinieve; van Houten, Nienke E.; Wang, Xin; Scott, Jamie K.

    2008-01-01

    Summary: Enormous efforts have been made to produce a protective vaccine against human immunodeficiency virus type 1; there has been little success. However, the identification of broadly neutralizing antibodies against epitopes on the highly conserved membrane-proximal external region (MPER) of the gp41 envelope protein has delineated this region as an attractive vaccine target. Furthermore, emerging structural information on the MPER has provided vaccine designers with new insights for building relevant immunogens. This review describes the current state of the field regarding (i) the structure and function of the gp41 MPER; (ii) the structure and binding mechanisms of the broadly neutralizing antibodies 2F5, 4E10, and Z13; and (iii) the development of an MPER-targeting vaccine. In addition, emerging approaches to vaccine design are presented. PMID:18322034

  16. Increased Sensitivity to CD4 Binding Site-Directed Neutralization following In Vitro Propagation on Primary Lymphocytes of a Neutralization-Resistant Human Immunodeficiency Virus IIIB Strain Isolated from an Accidentally Infected Laboratory Worker

    PubMed Central

    Beaumont, Tim; Quakkelaar, Esther; van Nuenen, Ad; Pantophlet, Ralph; Schuitemaker, Hanneke

    2004-01-01

    We previously described the adaptation of the neutralization-sensitive human immunodeficiency virus type 1 (HIV-1) strain IIIB to a neutralization-resistant phenotype in an accidentally infected laboratory worker. During long-term propagation of this resistant isolate, designated FF3346, on primary peripheral blood leukocytes in vitro, an HIV-1 variant appeared that had regained sensitivity to neutralization by soluble CD4 (sCD4) and the broadly neutralizing monoclonal antibody b12. When an early passage of FF3346 was subjected to limiting-dilution culture in peripheral blood mononuclear cells, eight virus variants with various degrees of neutralization resistance were isolated. Two of them, the sCD4 neutralization-resistant variant LW_H8res and the sCD4 neutralization-sensitive variant LW_G9sens, were selected for further study. Interestingly, these two viruses were equally resistant to neutralization by agents that recognize domains other than the CD4 binding site. Site-directed mutagenesis revealed that the increased neutralization sensitivity of variant LW_G9sens resulted from only two changes, an Asn-to-Ser substitution at position 164 in the V2 loop and an Ala-to-Glu substitution at position 370 in the C3 domain of gp120. In agreement with this notion, the affinity of b12 for monomeric gp120 containing the N164S and A370E substitutions in the background of the molecular clone LW_H8res was higher than its affinity for the parental gp120. Surprisingly, no correlation was observed between CD4 binding affinity for monomeric gp120 and the level of neutralization resistance, suggesting that differences in sCD4 neutralization sensitivity between these viruses are only manifested in the context of the tertiary or quaternary structure of gp120 on the viral surface. The results obtained here indicate that the neutralization-sensitive strain IIIB can become neutralization resistant in vivo under selective pressure by neutralizing antibodies but that this resistance may be easily reversed in the absence of immunological pressure. PMID:15140962

  17. Neutralizing polyclonal IgG present during acute infection prevents rapid disease onset in simian-human immunodeficiency virus SHIVSF162P3-infected infant rhesus macaques.

    PubMed

    Jaworski, J Pablo; Kobie, James; Brower, Zachary; Malherbe, Delphine C; Landucci, Gary; Sutton, William F; Guo, Biwei; Reed, Jason S; Leon, Enrique J; Engelmann, Flora; Zheng, Bo; Legasse, Al; Park, Byung; Dickerson, Mary; Lewis, Anne D; Colgin, Lois M A; Axthelm, Michael; Messaoudi, Ilhem; Sacha, Jonah B; Burton, Dennis R; Forthal, Donald N; Hessell, Ann J; Haigwood, Nancy L

    2013-10-01

    Simian-human immunodeficiency virus (SHIV) models for human immunodeficiency virus (HIV) infection have been widely used in passive studies with HIV neutralizing antibodies (NAbs) to test for protection against infection. However, because SHIV-infected adult macaques often rapidly control plasma viremia and any resulting pathogenesis is minor, the model has been unsuitable for studying the impact of antibodies on pathogenesis in infected animals. We found that SHIVSF162P3 infection in 1-month-old rhesus macaques not only results in high persistent plasma viremia but also leads to very rapid disease progression within 12 to 16 weeks. In this model, passive transfer of high doses of neutralizing IgG (SHIVIG) prevents infection. Here, we show that at lower doses, SHIVIG reduces both plasma and peripheral blood mononuclear cell (PBMC)-associated viremia and mitigates pathogenesis in infected animals. Moreover, production of endogenous NAbs correlated with lower set-point viremia and 100% survival of infected animals. New SHIV models are needed to investigate whether passively transferred antibodies or antibodies elicited by vaccination that fall short of providing sterilizing immunity impact disease progression or influence immune responses. The 1-month-old rhesus macaque SHIV model of infection provides a new tool to investigate the effects of antibodies on viral replication and clearance, mechanisms of B cell maintenance, and the induction of adaptive immunity in disease progression. PMID:23885083

  18. Neutralizing Polyclonal IgG Present during Acute Infection Prevents Rapid Disease Onset in Simian-Human Immunodeficiency Virus SHIVSF162P3-Infected Infant Rhesus Macaques

    PubMed Central

    Jaworski, J. Pablo; Kobie, James; Brower, Zachary; Malherbe, Delphine C.; Landucci, Gary; Sutton, William F.; Guo, Biwei; Reed, Jason S.; Leon, Enrique J.; Engelmann, Flora; Zheng, Bo; Legasse, Al; Park, Byung; Dickerson, Mary; Lewis, Anne D.; Colgin, Lois M. A.; Axthelm, Michael; Messaoudi, Ilhem; Sacha, Jonah B.; Burton, Dennis R.; Forthal, Donald N.; Hessell, Ann J.

    2013-01-01

    Simian-human immunodeficiency virus (SHIV) models for human immunodeficiency virus (HIV) infection have been widely used in passive studies with HIV neutralizing antibodies (NAbs) to test for protection against infection. However, because SHIV-infected adult macaques often rapidly control plasma viremia and any resulting pathogenesis is minor, the model has been unsuitable for studying the impact of antibodies on pathogenesis in infected animals. We found that SHIVSF162P3 infection in 1-month-old rhesus macaques not only results in high persistent plasma viremia but also leads to very rapid disease progression within 12 to 16 weeks. In this model, passive transfer of high doses of neutralizing IgG (SHIVIG) prevents infection. Here, we show that at lower doses, SHIVIG reduces both plasma and peripheral blood mononuclear cell (PBMC)-associated viremia and mitigates pathogenesis in infected animals. Moreover, production of endogenous NAbs correlated with lower set-point viremia and 100% survival of infected animals. New SHIV models are needed to investigate whether passively transferred antibodies or antibodies elicited by vaccination that fall short of providing sterilizing immunity impact disease progression or influence immune responses. The 1-month-old rhesus macaque SHIV model of infection provides a new tool to investigate the effects of antibodies on viral replication and clearance, mechanisms of B cell maintenance, and the induction of adaptive immunity in disease progression. PMID:23885083

  19. Infection of vaginal and colonic epithelial cells by the human immunodeficiency virus type 1 is neutralized by antibodies raised against conserved epitopes in the envelope glycoprotein gp120.

    PubMed Central

    Furuta, Y; Eriksson, K; Svennerholm, B; Fredman, P; Horal, P; Jeansson, S; Vahlne, A; Holmgren, J; Czerkinsky, C

    1994-01-01

    The rectal and genital tract mucosae are considered to be major sites of entry for the human immunodeficiency virus (HIV) during sexual contact. We now demonstrate that vaginal epithelial cells can be infected by HIV type 1 (HIV-1) via a mechanism similar to that described for neuroglial cells and, more recently, for colorectal epithelial cells, involving initial interaction of the HIV-1 envelope glycoprotein gp120 with a cell-surface glycosphingolipid (sulfated lactosylceramide). A hyperimmune serum against gp120 was able to neutralize HIV-1 infection of vaginal epithelial cells. Site-directed immunization was employed to identify sites on gp120 recognized by antibodies neutralizing HIV-1 infection of vaginal and colonic epithelial cells. Hyperimmune sera were raised in monkeys against a series of 40 overlapping synthetic peptides covering the entire sequence of HIV-1 (HTLV-IIIB) gp120. Antisera raised against five synthetic peptides, corresponding to three relatively conserved regions and to the hypervariable region (V3 loop), efficiently neutralized HIV-1 infection of human vaginal epithelial cells in vitro. Similar results were obtained with the colonic cells. Hyperimmune sera to all five peptides have been shown earlier to neutralize HIV-1 infectivity in CD4+ T cells. These results have obvious implications for the design of mucosal subunit vaccines against sexually transmitted HIV-1 infections. Images Fig. 1 Fig. 2 Fig. 3 PMID:7809077

  20. 21 CFR 660.50 - Anti-Human Globulin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 2010-04-01 false Anti-Human Globulin. 660.50 Section 660.50...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ...SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

  1. 21 CFR 660.50 - Anti-Human Globulin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...2012-04-01 2012-04-01 false Anti-Human Globulin. 660.50 Section 660.50...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ...SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

  2. 21 CFR 660.50 - Anti-Human Globulin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...2011-04-01 2010-04-01 true Anti-Human Globulin. 660.50 Section 660.50...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ...SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

  3. 21 CFR 660.50 - Anti-Human Globulin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...2014-04-01 2014-04-01 false Anti-Human Globulin. 660.50 Section 660.50...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ...SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

  4. 21 CFR 660.50 - Anti-Human Globulin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...2013-04-01 2013-04-01 false Anti-Human Globulin. 660.50 Section 660.50...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ...SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

  5. Human Immunodeficiency Virus Type 1 Neutralization Measured by Flow Cytometric Quantitation of Single-Round Infection of Primary Human T Cells

    PubMed Central

    Mascola, John R.; Louder, Mark K.; Winter, Christine; Prabhakara, Ranjani; De Rosa, Stephen C.; Douek, Daniel C.; Hill, Brenna J.; Gabuzda, Dana; Roederer, Mario

    2002-01-01

    There is currently intensive research on the design of novel human immunodeficiency virus type 1 (HIV-1) vaccine immunogens that can elicit potent neutralizing antibodies. A prerequisite for comparing and optimizing these strategies is the ability to precisely measure neutralizing antibody responses. To this end, we sought to develop an assay that directly quantifies single-round HIV-1 infection of peripheral blood mononuclear cells (PBMC). Initial experiments demonstrated that essentially all productively infected PBMC could be identified by flow cytometric detection of intracellular p24 antigen (p24-Ag). After infection of PBMC with HIV-1, p24+ lymphocytes could be distinguished beginning 1 day postinfection, and the majority of CD8? T cells were p24-Ag positive by 3 to 4 days postinfection. To directly quantify first-round infection, we included a protease inhibitor in PBMC cultures. The resulting 2-day assay was highly sensitive and specific for the detection of HIV-1-infected PBMC. Serial dilutions of virus stocks demonstrated that the number of target cells infected was directly related to the amount of infectious virus input into the assay. In neutralization assays, the flow cytometric enumeration of first-round infection of PBMC provided quantitative data on the number of target cells infected and on the inactivation of infectious virus due to reaction with antibody. We also used this single-round assay to compare the percentage of cells expressing p24-Ag to the number of copies of HIV-1 gag per 100 PBMC. The precision and reproducibility of this assay will facilitate the measurement of HIV-1 neutralization, particularly incrementally improved neutralizing antibody responses generated by new candidate vaccines. PMID:11967298

  6. Infection of Specific Dendritic Cells by CCR5-Tropic Human Immunodeficiency Virus Type 1 Promotes Cell-Mediated Transmission of Virus Resistant to Broadly Neutralizing Antibodies

    PubMed Central

    Ganesh, Lakshmanan; Leung, Kwanyee; Loré, Karin; Levin, Reuven; Panet, Amos; Schwartz, Owen; Koup, Richard A.; Nabel, Gary J.

    2004-01-01

    The tropism of human immunodeficiency virus type 1 for chemokine receptors plays an important role in the transmission of AIDS. Although CXCR4-tropic virus is more cytopathic for T cells, CCR5-tropic strains are transmitted more frequently in humans for reasons that are not understood. Phenotypically immature myeloid dendritic cells (mDCs) are preferentially infected by CCR5-tropic virus, in contrast to mature mDCs, which are not susceptible to infection but instead internalize virus into a protected intracellular compartment and enhance the infection of T cells. Here, we define a mechanism to explain preferential transmission of CCR5-tropic viruses based on their interaction with mDCs and sensitivity to neutralizing antibodies. Infected immature mDCs differentiated normally and were found to enhance CCR5-tropic but not CXCR4-tropic virus infection of T cells even in the continuous presence of neutralizing antibodies. Infectious synapses also formed normally in the presence of such antibodies. Infection of immature mDCs by CCR5-tropic virus can therefore establish a pool of infected cells that can efficiently transfer virus at the same time that they protect virus from antibody neutralization. This property of DCs may enhance infection, contribute to immune evasion, and could provide a selective advantage for CCR5-tropic virus transmission. PMID:15479838

  7. Formaldehyde-Treated, Heat-Inactivated Virions with Increased Human Immunodeficiency Virus Type 1 Env Can Be Used To Induce High-Titer Neutralizing Antibody Responses

    PubMed Central

    Poon, B.; Hsu, J. F.; Gudeman, V.; Chen, I. S. Y.; Grovit-Ferbas, K.

    2005-01-01

    The lack of success of subunit human immunodeficiency virus (HIV) type 1 vaccines to date suggests that multiple components or a complex virion structure may be required. We hypothesized that the failure of current vaccine strategies to induce protective antibodies is linked to the inability of native envelope structures to readily elicit these types of antibodies. We have previously reported on the ability of a formaldehyde-treated, heat-inactivated vaccine to induce modest antibody responses in animal vaccine models. We investigated here whether immunization for HIV with an envelope-modified, formaldehyde-stabilized, heat-inactivated virion vaccine could produce higher-titer and/or broader neutralizing antibody responses. Thus, a clade B vaccine which contains a single point mutation in gp41 (Y706C) that results in increased incorporation of oligomeric Env into virions was constructed. This vaccine was capable of inducing high-titer antibodies that could neutralize heterologous viruses, including those of clades A and C. These results further support the development of HIV vaccines with modifications in native Env structures for the induction of neutralizing antibody responses. PMID:16051814

  8. Modeling how many envelope glycoprotein trimers per virion participate in human immunodeficiency virus infectivity and its neutralization by antibody

    Microsoft Academic Search

    Per Johan Klasse

    2007-01-01

    Trimers of the HIV-1 envelope glycoprotein (Env) effectuate viral entry into susceptible cells. Therefore Env trimers are the targets for neutralizing antibodies. This study models the number of trimers required for virion infectivity. It also delineates the minimum number of antibody molecules that would neutralize a virion. First, Env function was assumed to be incremental (all envelope glycoprotein units contribute

  9. Identification of a Novel WxSLVK Motif in the N Terminus of Human Immunodeficiency Virus and Simian Immunodeficiency Virus Vif That Is Critical for APOBEC3G and APOBEC3F Neutralization?

    PubMed Central

    Dang, Ying; Wang, Xiaojun; Zhou, Tao; York, Ian A.; Zheng, Yong-Hui

    2009-01-01

    The function of lentiviral Vif proteins is to neutralize the host antiviral cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F). Vif bridges a cullin 5-based E3 ubiquitin ligase with A3G and A3F and mediates their degradation by proteasomes. Recent studies have found that Vif uses different domains to bind to A3G and A3F. A 14DRMR17 domain binds to A3F, 40YRHHY44 binds to A3G, and 69YxxL72 binds to both A3G and A3F. Here, we report another functional domain of Vif. Previously, we demonstrated that human immunodeficiency virus type 1 (HIV-1) Vif failed to mediate A3G proteasomal degradation when all 16 lysines were mutated to arginines. Here, we show that K26, and to a lesser extent K22, is critical for A3G neutralization. K22 and K26 are part of a conserved 21WxSLVK26 (x represents N, K, or H) motif that is found in most primate lentiviruses and that shows species-specific variation. Both K22 and K26 in this motif regulated Vif specificity only for A3G, whereas the SLV residues regulated Vif specificity for both A3F and A3G. Interestingly, SLV and K26 in HIV-1 Vif did not directly mediate Vif interaction with either A3G or A3F. Previously, other groups have reported an important role for W21 in A3F and A3G neutralization. Thus, 21WxSLVK26 is a novel functional domain that regulates Vif activity toward both A3F and A3G and is a potential drug target to inhibit Vif activity and block HIV-1 replication. PMID:19535447

  10. Cross-Reactive Human Immunodeficiency Virus Type 1-Neutralizing Human Monoclonal Antibody That Recognizes a Novel Conformational Epitope on gp41 and Lacks Reactivity against Self-Antigens ?

    PubMed Central

    Zhang, Mei-Yun; Vu, Bang K.; Choudhary, Anil; Lu, Hong; Humbert, Michael; Ong, Helena; Alam, Munir; Ruprecht, Ruth M.; Quinnan, Gerald; Jiang, Shibo; Montefiori, David C.; Mascola, John R.; Broder, Christopher C.; Haynes, Barton F.; Dimitrov, Dimiter S.

    2008-01-01

    Broadly cross-reactive human immunodeficiency virus (HIV)-neutralizing antibodies are infrequently elicited in infected humans. The two best-characterized gp41-specific cross-reactive neutralizing human monoclonal antibodies, 4E10 and 2F5, target linear epitopes in the membrane-proximal external region (MPER) and bind to cardiolipin and several other autoantigens. It has been hypothesized that, because of such reactivity to self-antigens, elicitation of 2F5 and 4E10 and similar antibodies by vaccine immunogens based on the MPER could be affected by tolerance mechanisms. Here, we report the identification and characterization of a novel anti-gp41 monoclonal antibody, designated m44, which neutralized most of the 22 HIV type 1 (HIV-1) primary isolates from different clades tested in assays based on infection of peripheral blood mononuclear cells by replication-competent virus but did not bind to cardiolipin and phosphatidylserine in an enzyme-linked immunosorbent assay and a Biacore assay nor to any protein or DNA autoantigens tested in Luminex assays. m44 bound to membrane-associated HIV-1 envelope glycoproteins (Envs), to recombinant Envs lacking the transmembrane domain and cytoplasmic tail (gp140s), and to gp41 structures containing five-helix bundles and six-helix bundles, but not to N-heptad repeat trimers, suggesting that the C-heptad repeat is involved in m44 binding. In contrast to 2F5, 4E10, and Z13, m44 did not bind to any significant degree to denatured gp140 and linear peptides derived from gp41, suggesting a conformational nature of the epitope. This is the first report of a gp41-specific cross-reactive HIV-1-neutralizing human antibody that does not have detectable reactivity to autoantigens. Its novel conserved conformational epitope on gp41 could be helpful in the design of vaccine immunogens and as a target for therapeutics. PMID:18480433

  11. Removal of a Single N-Linked Glycan in Human Immunodeficiency Virus Type 1 gp120 Results in an Enhanced Ability To Induce Neutralizing Antibody Responses?

    PubMed Central

    Li, Yun; Cleveland, Bradley; Klots, Igor; Travis, Bruce; Richardson, Barbra A.; Anderson, David; Montefiori, David; Polacino, Patricia; Hu, Shiu-Lok

    2008-01-01

    Glycans on human immunodeficiency virus (HIV) envelope protein play an important role in infection and evasion from host immune responses. To examine the role of specific glycans, we introduced single or multiple mutations into potential N-linked glycosylation sites in hypervariable regions (V1 to V3) of the env gene of HIV type 1 (HIV-1) 89.6. Three mutants tested showed enhanced sensitivity to soluble CD4. Mutant N7 (N197Q) in the carboxy-terminal stem of the V2 loop showed the most pronounced increase in sensitivity to broadly neutralizing antibodies (NtAbs), including those targeting the CD4-binding site (IgG1b12) and the V3 loop (447-52D). This mutant is also sensitive to CD4-induced NtAb 17b in the absence of CD4. Unlike the wild-type (WT) Env, mutant N7 mediates CD4-independent infection in U87-CXCR4 cells. To study the immunogenicity of mutant Env, we immunized pig-tailed macaques with recombinant vaccinia viruses, one expressing SIVmac239 Gag-Pol and the other expressing HIV-1 89.6 Env gp160 in WT or mutant forms. Animals were boosted 14 to 16 months later with simian immunodeficiency virus gag DNA and the cognate gp140 protein before intrarectal challenge with SHIV89.6P-MN. Day-of-challenge sera from animals immunized with mutant N7 Env had significantly higher and broader neutralizing activities than sera from WT Env-immunized animals. Neutralizing activity was observed against SHIV89.6, SHIV89.6P-MN, HIV-1 SF162, and a panel of subtype B primary isolates. Compared to control animals, immunized animals showed significant reduction of plasma viral load and increased survival after challenge, which correlated with prechallenge NtAb titers. These results indicate the potential advantages for glycan modification in vaccine design, although the role of specific glycans requires further examination. PMID:17959660

  12. Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response

    PubMed Central

    2013-01-01

    Background Differently from HIV-1, HIV-2 disease progression usually takes decades without antiretroviral therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4+ T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected at birth. Results CD4+ T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4+ T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a ?-hairpin structure were related with rate of escape from the neutralizing antibodies. Conclusion Our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis. PMID:24156513

  13. Neutralizing antibodies against the V3 loop of human immunodeficiency virus type 1 gp120 block the CD4-dependent and -independent binding of virus to cells.

    PubMed Central

    Valenzuela, A; Blanco, J; Krust, B; Franco, R; Hovanessian, A G

    1997-01-01

    The CD4 molecule is an essential receptor for human immunodeficiency virus type 1 (HIV-1) through high-affinity interactions with the viral external envelope glycoprotein gp120. Previously, neutralizing monoclonal antibodies (MAbs) specific to the third hypervariable domain of gp120 (the V3 loop) have been thought to block HIV infection without affecting the binding of HIV particles to CD4-expressing human cells. However, here we demonstrate that this conclusion was not correct and was due to the use of soluble gp120 instead of HIV particles. Indeed, neutralizing anti-V3 loop MAbs inhibited completely the binding and entry of HIV particles into CD4+ human cells. In contrast, the binding of virus was only partially inhibited by neutralizing anti-CD4 MAbs against the gp120 binding site in CD4, which, like the anti-V3 loop MAbs, completely inhibited HIV entry and infection. Nonneutralizing control MAbs against either the V3 loop or the N or C terminus of gp120 had no significant effect on HIV binding and entry. HIV-1 particles were also found to bind human and murine cells expressing or not expressing the human CD4 molecule. Interestingly, the binding of HIV to CD4+ murine cells was inhibited by both anti-V3 and anti-CD4 MAbs, whereas the binding to human and murine CD4- cells was affected only by anti-V3 loop MAbs. The effect of anti-V3 loop neutralizing MAbs on the HIV binding to cells appears not to be the direct consequence of gp120 shedding from HIV particles or of a decreased affinity of CD4 or gp120 for binding to its surface counterpart. Taken together, our results suggest the existence of CD4-dependent and -independent binding events involved in the attachment of HIV particles to cells; in both of these events, the V3 loop plays a critical role. As murine cells lack the specific cofactor CXCR4 for HIV-1 entry, other cell surface molecules besides CD4 might be implicated in stable binding of HIV particles to cells. PMID:9343181

  14. Prechallenge high neutralizing antibodies and long-lasting immune reactivity to gp41 correlate with protection of rhesus monkeys against productive simian immunodeficiency virus infection or disease development.

    PubMed

    Petry, H; Dittmer, U; Jones, D; Farrar, G; Wachter, H; Fuchs, D; Nisslein, T; Jurkiewicz, E; Hunsmann, G; Stahl-Hennig, C; Lüke, W

    1998-12-15

    To investigate the protective efficacy of various gp130 vaccine preparations, rhesus monkeys were immunized with gp130 oligomers (O-gp130) or two different gp130-monomer preparations (M1-gp130; M2-gp130) and challenged with 50 MID50 of simian immunodeficiency virus (SIV)mac32H. Following challenge the control animals and all animals of the M1- and M2-gp130 group and 1 animal of the O-gp130 group were productively infected, whereas 3 animals of the O-gp130 group resisted the productive virus replication. The protection was correlated with high neutralizing antibodies and a long-lasting immune response to the transmembrane protein gp41. Whereas none of the O-gp130 animals had developed disease symptoms, 3 M1-gp130 animals, 1 M2-gp130 animal, and 2 control animals died as a result of AIDS within 18 months after challenge. Therefore, immunization with virion-derived gp130 oligomers of SIVmac32H can confer protection against the productive infection with SIVmac32H and suppress the development of the AIDS-like disease. PMID:9859957

  15. Modeling how many envelope glycoprotein trimers per virion participate in human immunodeficiency virus infectivity and its neutralization by antibody.

    PubMed

    Klasse, Per Johan

    2007-12-20

    Trimers of the HIV-1 envelope glycoprotein (Env) effectuate viral entry into susceptible cells. Therefore Env trimers are the targets for neutralizing antibodies. This study models the number of trimers required for virion infectivity. It also delineates the minimum number of antibody molecules that would neutralize a virion. First, Env function was assumed to be incremental (all envelope glycoprotein units contribute equally) or liminal (characterized by thresholds). Then, such models were combined and shown to fit published data on phenotypically mixed pseudotype viruses. Virions with 9 trimers would require around a median of 5 of them for strong infectivity; the proportion varies among strains and mutants. In addition, the models account for both liminal and incremental protomeric effects at the trimer level: different inert Env mutants may affect trimer function in different degrees. Because of compensatory effects at the virion and trimer levels, however, current data cannot differentiate between all plausible models. But the biophysically and mathematically rationalized blurring of thresholds yields candidate models that fit different data excellently. PMID:17825343

  16. Covalently Linked Human Immunodeficiency Virus Type 1 gp120/gp41 Is Stably Anchored in Rhabdovirus Particles and Exposes Critical Neutralizing Epitopes

    PubMed Central

    McKenna, Philip M.; Pomerantz, Roger J.; Dietzschold, Bernhard; McGettigan, James P.; Schnell, Matthias J.

    2003-01-01

    Rabies virus (RV) vaccine strain-based vectors show significant promise as potential live-attenuated vaccines against human immunodeficiency virus type 1 (HIV-1). Here we describe a new RV construct that will also likely have applications as a live-attenuated or killed-particle immunogen. We have created a RV containing a chimeric HIV-1 Env protein, which contains introduced cysteine residues that give rise to an intermolecular disulfide bridge between gp120 and the ectodomain of gp41. This covalently linked gp140 (gp140 SOS) is fused in frame to the cytoplasmic domain of RV G glycoprotein and is efficiently incorporated into the RV virion. On the HIV-1 virion, the gp120 and gp41 moieties are noncovalently associated, which leads to extensive shedding of gp120 from virions and virus-infected cells. The ability to use HIV-1 particles as purified, inactivated immunogens has been confounded by the loss of gp120 during preparation. Additionally, monomeric gp120 and uncleaved gp160 molecules have been shown to be poor antigenic representations of virion-associated gp160. Because the gp120 and gp41 portions are covalently attached in the gp140 SOS molecule, the protein is maintained on the surface of the RV virion throughout purification. Surface immunostaining and fluorescence-activated cell sorting analysis with anti-envelope antibodies show that the gp140 SOS protein is stably expressed on the surface of infected cells and maintains CD4 binding capabilities. Furthermore, Western blot and immunoprecipitation experiments with infected-cell lysates and purified virions show that a panel of neutralizing anti-envelope antibodies efficiently recognize the gp140 SOS protein. The antigenic properties of this recombinant RV particle containing covalently attached Env, as well as the ability to present Env in a membrane-bound form, suggest that this approach could be a useful component of a HIV-1 vaccine strategy. PMID:14610200

  17. Dextran sulfate blocks antibody binding to the principal neutralizing domain of human immunodeficiency virus type 1 without interfering with gp120-CD4 interactions.

    PubMed Central

    Callahan, L N; Phelan, M; Mallinson, M; Norcross, M A

    1991-01-01

    The mechanism of the antiviral activity of sulfated polysaccharides on human immunodeficiency virus type 1 (HIV-1) was investigated by determining the effect of dextran sulfate on the binding of CD4 and several anti-gp120 monoclonal antibodies to both recombinant and cell surface gp120. Dextran sulfate did not interfere with the binding of sCD4 to rgp120 on enzyme-linked immunosorbent assay (ELISA) plates or in solution and did not block sCD4 binding to HIV-1-infected cells expressing gp120 on the cell surface. Dextran sulfate had minimal effects on rgp120 binding to CD4+ cells at concentrations which effectively prevent HIV replication. In contrast, it potently inhibited the binding of both rgp120 and cell surface gp120 to several monoclonal antibodies directed against the principal neutralizing domain of gp120 (V3). In an ELISA format, dextran sulfate enhanced the binding of monoclonal antibodies against amino-terminal regions of gp120 and had no effect on antibodies directed to other regions of gp120, including the carboxy terminus. The inhibitory effects of polyanionic polysaccharides on viral binding, viral replication, and formation of syncytia therefore appear mediated by interactions with positively charged amino acids concentrated in the V3 region. This high local positive charge density, unique to the V3 loop, leads us to propose that this property is critical to the function of the V3 region in mediating envelope binding and subsequent fusion between viral and cell membranes. The specific interaction of dextran sulfate with this domain suggests that structurally related molecules on the cell surface, such as heparan sulfate, may be additional targets for HIV binding and infection. PMID:1995952

  18. Analysis and validation of the phosphorylated metabolites of two anti-human immunodeficiency virus nucleotides (stavudine and didanosine) by pressure-assisted CE-ESI-MS/MS in cell extracts: sensitivity enhancement by the use of perfluorinated acids and alcohols as coaxial sheath-liquid make-up constituents.

    PubMed

    Bezy, Vincent; Chaimbault, Patrick; Morin, Philippe; Unger, Steve E; Bernard, Marie-Charlotte; Agrofoglio, Luigi A

    2006-06-01

    A CE method utilizing triple quadrupole electrospray (ES) MS (MS/MS) detection was developed and validated for the simultaneous measurement of nucleoside 5'-triphosphate and 5'-monophosphate anabolites of the anti-HIV (human immunodeficiency virus) didanosine (ddAMP, ddATP) and stavudine (d4TMP, d4TTP), among a pool of 14 endogenous 5'-mono-, di-, and triphosphate nucleosides. These compounds were spiked and extracted from peripheral blood mononuclear cells (PBMCs) which are the sites of HIV replication and drug action. An acetic acid/ammonia buffer (pH 10, ionic strength of 40 mM) was selected as running electrolyte, and the separation was performed by the simultaneous application of a CE voltage of +30 kV and an overimposed pressure of 28 mbar (0.4 psi). The application of pressure assistance was needed to provide stable ES conditions for successful coupling. The coupling was carried out with a modified sheath-flow interface, with one uninterrupted capillary (80 cmx 50 microm id; 192 microm od) in a dimension that fits into the ESI needle to get a stable ion spray. Some CE-MS parameters such as overimposed pressure, sheath-liquid composition, sheath-liquid and sheath-gas flow rates, ES voltage, and the CE capillary position were optimized in order to obtain an optimal sensitivity. The use of perfluorinated alcohols and acids in the coaxial sheath-liquid make-up (2,2,2-trifluoroethanol + 0.2 mM tridecafluoroheptanoic acid) appeared to provide the best MS sensitivity and improve the stability of spray. The linearity of the CE-MS and CE-MS/MS methods was checked under these conditions. Validation parameters such as accuracy, intraday and interday precision, and LOQs were determined in CE-MS/MS mode. Finally, the quantitation of d4T-TP and ddA-TP was validated in this CE-MS/MS system. PMID:16786481

  19. Immunodeficiency disorders

    MedlinePLUS

    ... foreign blood or tissues from another person or species. When the immune system detects an antigen, it ... disorders that affect T cells may cause repeated Candida (yeast) infections. Inherited combined immunodeficiency affects both T ...

  20. Vaccine-induced virus-neutralizing antibodies and cytotoxic T cells do not protect macaques from experimental infection with simian immunodeficiency virus SIVmac32H (J5)

    Microsoft Academic Search

    ELLEN G. J. HULSKOTTE; ANNA-MARIA GERETTI; C. H. J. Siebelink; Amerongen van G; MARTIN P. CRANAGE; ERLING W. RUD; STEPHEN G. NORLEY; Vries de P; ALBERT D. M. E. OSTERHAUS

    1995-01-01

    To gain further insight into the ability of subunit vaccines to protect monkeys from experimental infection with simian immunodeficiency virus (SIV), two groups of cynomolgus macaques were immunized with either recombinant SIVmac32H-derived envelope glycoproteins (Env) incorporated into immune-stimulating complexes (iscoms) (group A) or with these SIV Env iscoms in combination with p27gag iscoms and three Nef lipopeptides (group B). Four

  1. Quantitative Molecular Monitoring of Human Immunodeficiency Virus Type 1 Activity during Therapy with Specific Antiretroviral Compounds

    Microsoft Academic Search

    PATRIZIA BAGNARELLI; STEFANO MENZO; ANNA VALENZA; STEFANIA PAOLUCCI; SONIA PETRONI; GIORGIO SCALISE; RICCARDO SAMPAOLESI; ALDO MANZIN; PIETRO E. VARALDO; ANDMASSIMO CLEMENTI

    1995-01-01

    Methods for the absolute quantitation of nucleic acids present in small amounts in biological samples (competitive PCR and competitive reverse transcription PCR) were applied to the direct monitoring of specific anti-human immunodeficiency virus type 1 (HIV-1) therapy. With these techniques, different parameters of HIV-1 activity (including genomic RNA copy numbers in plasma, proviral and late transcript copy numbers in peripheral

  2. Immunogenic and antigenic dominance of a nonneutralizing epitope over a highly conserved neutralizing epitope in the gp41 envelope glycoprotein of human immunodeficiency virus type 1: its deletion leads to a strong neutralizing response

    Microsoft Academic Search

    S. Matthew Cleveland; Emanuele Buratti; Tim D. Jones; Philip North; Francisco Baralle; Lesley McLain; Tracey McInerney; Zarmina Durrani; Nigel J. Dimmock

    2000-01-01

    The Kennedy peptide, (731)PRGPDRPEGIEEEGGERDRDRS(752), from the cytoplasmic domain of the gp41 transmembrane envelope glycoprotein of HIV-1 contains a conformationally dependent neutralizing epitope (ERDRD) and a linear nonneutralizing epitope (IEEE). No recognized murine T cell epitope is present. The peptide usually stimulates virus- specific antibody, but this is not always neutralizing. Here we show that IEEE (or possibly IEEE plus adjacent

  3. Immunization of rabbits with highly purified, soluble, trimeric human immunodeficiency virus type 1 envelope glycoprotein induces a vigorous B cell response and broadly cross-reactive neutralization.

    PubMed

    Quinnan, Gerald V; Onabajo, Olusegun; Zhang, Pengfei; Yan, Lianying; Mattapallil, Joseph J; Zhang, Zhiqiang; Dong, Ming; Lu, Min; Montefiori, David; LaBranche, Celia; Broder, Christopher C

    2014-01-01

    Previously we described induction of cross-reactive HIV-1 neutralizing antibody responses in rabbits using a soluble HIV-1 gp140 envelope glycoprotein (Env) in an adjuvant containing monophosphoryl lipid A (MPL) and QS21 (AS02A). Here, we compared different forms of the same HIV-1 strain R2 Env for antigenic and biophysical characteristics, and in rabbits characterized the extent of B cell induction for specific antibody expression and secretion and neutralizing responses. The forms of this Env that were produced in and purified from stably transformed 293T cells included a primarily dimeric gp140, a trimeric gp140 appended to a GCN4 trimerization domain (gp140-GCN4), gp140-GCN4 with a 15 amino acid flexible linker between the gp120 and gp41 ectodomain (gp140-GCN4-L), also trimeric, and a gp140 with the flexible linker purified from cell culture supernatants as either dimer (gp140-L(D)) or monomer (gp140-L(M)). Multimeric states of the Env proteins were assessed by native gel electrophoresis and analytical ultracentrifugation. The different forms of gp140 bound broadly cross-reactive neutralizing (BCN) human monoclonal antibodies (mAbs) similarly in ELISA and immunoprecipitation assays. All Envs bound CD4i mAbs in the presence and absence of sCD4, as reported for the R2 Env. Weak neutralization of some strains of HIV-1 was seen after two additional doses in AS02A. Rabbits that were given a seventh dose of gp140-GCN4-L developed BCN responses that were weak to moderate, similar to our previous report. The specificity of these responses did not appear similar to that of any of the known BCN human mAbs. Induction of spleen B cell and plasma cells producing immunoglobulins that bound trimeric gp140-GCN4-L was vigorous, based on ELISpot and flow cytometry analyses. The results demonstrate that highly purified gp140-GCN4-L trimer in adjuvant elicits BCN responses in rabbits accompanied by vigorous B cell induction. PMID:24846288

  4. Stable Docking of Neutralizing Human Immunodeficiency Virus Type 1 gp41 Membrane-Proximal External Region Monoclonal Antibodies 2F5 and 4E10 Is Dependent on the Membrane Immersion Depth of Their Epitope Regions ?

    PubMed Central

    Dennison, S. Moses; Stewart, Shelley M.; Stempel, Kathryn C.; Liao, Hua-Xin; Haynes, Barton F.; Alam, S. Munir

    2009-01-01

    The binding of neutralizing antibodies 2F5 and 4E10 to human immunodeficiency virus type 1 (HIV-1) gp41 involves both the viral membrane and gp41 membrane proximal external region (MPER) epitopes. In this study, we have used several biophysical tools to examine the secondary structure, orientation, and depth of immersion of gp41 MPER peptides in liposomes and to determine how the orientation of the MPER with lipids affects the binding kinetics of monoclonal antibodies (MAbs) 2F5 and 4E10. The binding of 2F5 and 4E10 both to their respective nominal epitopes and to a biepitope (includes 2F5 and 4E10 epitopes) MPER peptide-liposome conjugate was best described by a two-step encounter-docking model. Analysis of the binding kinetics and the effect of temperature on the binding stability of 2F5 and 4E10 to MPER peptide-liposome conjugates revealed that the docking of 4E10 was relatively slower and thermodynamically less favorable. The results of fluorescence-quenching and fluorescence resonance energy transfer experiments showed that the 2F5 epitope was more solvent exposed, whereas the 4E10 epitope was immersed in the polar-apolar interfacial region of the lipid bilayer. A circular dichroism spectroscopic study demonstrated that the nominal epitope and biepitope MPER peptides adopted ordered structures with differing helical contents when anchored to liposomes. Furthermore, anchoring of MPER peptides to the membrane via a hydrophobic anchor sequence was required for efficient MAb docking. These results support the model that the ability of 2F5 and 4E10 to bind to membrane lipid is required for stable docking to membrane-embedded MPER residues. These data have important implications for the design and use of peptide-liposome conjugates as immunogens for the induction of MPER-neutralizing antibodies. PMID:19640992

  5. Prevalence of anti-human respiratory syncytial virus antibodies over three consecutive years in a healthy adult population.

    PubMed

    Chala, Silvia R; García-Barreno, Blanca; Melero, José A; Palomo, Concepción

    2003-10-01

    The titers of anti-human respiratory syncytial virus (HRSV) antibodies have been measured by enzyme-linked immunosorbent assay (ELISA) in a cohort of healthy adult volunteers over 3 consecutive years. Significant increases in the level of these antibodies were detected in a small percentage of individuals (3-3.3%), when paired serum samples taken from two consecutive seasons were compared. In these cases, a significant increase was generally noted in the level of antibodies directed against either the F or the G glycoproteins, and in the level of neutralizing antibodies. However, no correlation was found between the level of binding and neutralizing antibodies, when samples representative of the population under study were analyzed. These results indicate some level of infection by HRSV in the adult population. The implications of these results for the epidemiology of HRSV are discussed. PMID:12938206

  6. Scorpion-Toxin Mimics of CD4 in Complex with Human Immunodeficiency Virus gp120: Crystal Structures, Molecular Mimicry, and Neutralization Breadth

    SciTech Connect

    Huang, Chih-chin; Stricher, Francois; Martin, Loic; Decker, Julie M.; Majeed, Shahzad; Barthe, Phillippe; Hendrickson, Wayne A.; Robinson, James; Roumestand, Christian; Sodroski, Joseph; Wyatt, Richard; Shaw, George M.; Vita, Claudio; Kwong, Peter D. (Havard-Med); (NIH); (UAB); (Columbia); (CEA Saclay); (Tulane); (Faculty of Pharmacy)

    2010-07-19

    The binding surface on CD4 for the HIV-1 gp120 envelope glycoprotein has been transplanted previously onto a scorpion-toxin scaffold. Here, we use X-ray crystallography to characterize atomic-level details of gp120 with this transplant, CD4M33. Despite known envelope flexibility, the conformation of gp120 induced by CD4M33 was so similar to that induced by CD4 that localized measures were required to distinguish ligand-induced differences from lattice variation. To investigate relationships between structure, function, and mimicry, an F23 analog of CD4M33 was devised. Structural and thermodynamic analyses showed F23 to be a better molecular mimic of CD4 than CD4M33. F23 also showed increased neutralization breadth, against diverse isolates of HIV-1, HIV-2, and SIVcpz. Our results lend insight into the stability of the CD4 bound conformation of gp120, define measures that quantify molecular mimicry as a function of evolutionary distance, and suggest how such evaluations might be useful in developing mimetic antagonists with increased neutralization breadth.

  7. [Autoimmune hypoglycemia syndrome with specific anti-human insulin antibodies].

    PubMed

    Cresto, J C; Abdenur, J E; Chamoles, N; Bresciani, P; Ruiz, M; Massa, B; Camberos, M C; Basabe, J C

    1996-01-01

    A 33 year old woman with episodes of severe hypoglycemia is presented. The studies showed anti-insulin antibodies and variable C-peptide levels. Circulating insulin measured after acid-ethanol extraction, was of 1,600 uU/ml and shown to be human insulin after characterization by HLPC. Specific anti-human insulin antibodies were of high affinity (Ka1: 6.20 x 10(10) M-1; Ka2: 2.42 x 10(9) M-1). A small cross-reactive porcine and bovine antibody subpopulation was also detected (IgG, light k type chain). Plasmapheresis was undertaken when symptoms were spontaneously declining and turned antibody title negative. Prolonged follow-up showed no relapse of this syndrome. PMID:9035485

  8. Flow cytometric immunophenotyping of feline bone marrow cells and haematopoietic progenitor cells using anti-human antibodies.

    PubMed

    Araghi, Atefeh; Nassiri, Seyed Mahdi; Atyabi, Nahid; Rahbarghazi, Reza; Mohammadi, Elham

    2014-04-01

    There is a paucity of species-specific antibodies available for feline haematopoietic conditions. The purpose of this study was to broaden the panel of antibodies available for use in the immunophenotypic characterisation of feline haematopoietic cells by testing clones of anti-human monoclonal antibodies (mAbs) on normal, neoplastic and cultured feline haematopoietic progenitors to determine cross-reactivity to feline counterparts. In this study, 24 clones of anti-human mAbs were tested on normal or neoplastic feline bone marrow and peripheral blood cells. Six of these mAbs, including anti-cluster of differentiation (CD)61, anti-CD18, anti-CD14, anti-CD235a, anti-CD41 and anti-CD29, cross-reacted with normal feline bone marrow cells, whereas anti-CD33 and anti-CD117 cross-reacted with the blast cells in the bone marrow of two cats with myelodysplastic syndrome, and anti-CD71, anti-235a, anti-41 and anti-42 cross-reacted with immature erythroid cells in a cat with erythroleukaemia. In a feline immunodeficiency virus-positive cat, bone marrow cells were labelled with anti-CD33, anti-14 and anti-45. Anti-CD18, anti-CD14, anti-CD41 and anti-CD61 also reacted with the peripheral blood cells of the healthy cats. The feline haematopoietic progenitors formed colonies in the methylcellulose-based semisolid medium with significant enrichment of colony-forming unit-granulocyte, monocyte and burst-forming unit-erythroid. A panel of six anti-feline mAbs (anti-CD21-like, anti-T lymphocytes, anti-CD172a, anti-granulocyte, anti-CD45-like and anti-CD18) and eight anti-human antibodies (anti-CD71, anti-CD33, anti-CD235a, anti-CD41, anti-CD61, anti-CD117, anti-CD38 and anti-CD34) were used for the immunophenotypic characterisation of the feline bone marrow progenitors. CD45, CD33, CD235a and CD18 were expressed by the feline haematopoietic progenitor cells, with the highest expression level for CD45. PMID:24065708

  9. Structure-Based Design of a Protein Immunogen that Displays an HIV-1 gp41 Neutralizing Epitope

    SciTech Connect

    Stanfield, Robyn L.; Julien, Jean-Philippe; Pejchal, Robert; Gach, Johannes S.; Zwick, Michael B.; Wilson, Ian A. (Scripps)

    2012-06-27

    Antibody Z13e1 is a relatively broadly neutralizing anti-human immunodeficiency virus type 1 antibody that recognizes the membrane-proximal external region (MPER) of the human immunodeficiency virus type 1 envelope glycoprotein gp41. Based on the crystal structure of an MPER epitope peptide in complex with Z13e1 Fab, we identified an unrelated protein, interleukin (IL)-22, with a surface-exposed region that is structurally homologous in its backbone to the gp41 Z13e1 epitope. By grafting the gp41 Z13e1 epitope sequence onto the structurally homologous region in IL-22, we engineered a novel protein (Z13-IL22-2) that contains the MPER epitope sequence for use as a potential immunogen and as a reagent for the detection of Z13e1-like antibodies. The Z13-IL22-2 protein binds Fab Z13e1 with a K{sub d} of 73 nM. The crystal structure of Z13-IL22-2 in complex with Fab Z13e1 shows that the epitope region is faithfully replicated in the Fab-bound scaffold protein; however, isothermal calorimetry studies indicate that Fab binding to Z13-IL22-2 is not a lock-and-key event, leaving open the question of whether conformational changes upon binding occur in the Fab, in Z13-IL-22, or in both.

  10. SolidPhase Proteoliposomes Containing Human Immunodeficiency Virus Envelope Glycoproteins

    Microsoft Academic Search

    Christoph Grundner; Tajib Mirzabekov; Joseph Sodroski; Richard Wyatt

    2002-01-01

    The human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein gp120 mediates receptor binding and is the major target for neutralizing antibodies. A broadly neutralizing antibody response is likely to be a critical component of the immune response against HIV-1. Although antibodies against monomeric gp120 are readily elicited in immunized individuals, these antibodies are inefficient in neutralizing primary HIV-1 isolates.

  11. Stimulation of neutralizing antibodies to human immunodeficiency virus type 1 in three strains of mice immunized with a 22 amino acid peptide of gp41 expressed on the surface of a plant virus

    Microsoft Academic Search

    Lesley McLain; Zarmina Durrani; Lisa Ann Wisniewski; Claudine Porta; George P. Lomonossoff; Nigel J. Dimmock

    1996-01-01

    A plant virus, cowpea mosaic virus, expressing a 22 amino acid peptide 731–752 of the gp41 glycoprotein of human immunodeficency virus type 1 (HIV-1 IIIB), was shown previously to stimulate HIV-1 cross reactive neutralizing antibodies in adult C57BL6 mice. Here some parameters concerning the stimulation of HIV-1-specific neutralizing and ELISA antibody have been determined in adult C57BL6, C3HHe-mg and BALBc

  12. Common variable immunodeficiency

    PubMed Central

    Tam, Jonathan S.

    2013-01-01

    Common variable immunodeficiency (CVID) is a common primary immunodeficiency characterized by a failure in B-cell differentiation with defective immunoglobulin production. Affected patients are uniquely susceptible to recurrent infection with encapsulated organisms and have an increased propensity for the development of inflammatory and autoimmune manifestations. The diagnosis of CVID is commonly delayed and the underlying cause of the disorder is not understood. Replacement antibody therapy reduces the risk of serious infections. However, optimal treatment regimens for the uncommon manifestations associated with this disease, such as granulomatous lymphocytic interstitial lung disease, require further research. PMID:23883805

  13. Synthetic multimeric peptides derived from the principal neutralization domain (V3 loop) of human immunodeficiency virus type 1 (HIV-1) gp120 bind to galactosylceramide and block HIV-1 infection in a human CD4-negative mucosal epithelial cell line.

    PubMed Central

    Yahi, N; Sabatier, J M; Baghdiguian, S; Gonzalez-Scarano, F; Fantini, J

    1995-01-01

    The glycosphingolipid galactosylceramide (GalCer), which binds gp120 with high affinity and specificity, is a potential alternative receptor for human immunodeficiency virus type 1 (HIV-1) in some CD4-negative neural and epithelial human cells, including the human colonic epithelial cell line HT-29. In the present study, we demonstrate that synthetic multibranched peptides derived from the consensus sequence of the HIV-1 V3 loop block HIV-1 infection in HT-29 cells. The most active peptide was an eight-branched multimer of the motif Gly-Pro-Gly-Arg-Ala-Phe which at a concentration of 1.8 microM induced a 50% inhibition of HIV-1 infection in competition experiments. This peptide was not toxic to HT-29 cells, and preincubation with HIV-1 did not affect viral infectivity, indicating that the antiviral activity was not due to a nonspecific virucidal effect. Using a high-performance thin-layer chromatography binding assay, we found that multibranched V3 peptides recognized GalCer and inhibited binding of recombinant gp120 to the glycosphingolipid. In addition, these peptides abolished the binding of an anti-GalCer monoclonal antibody to GalCer on the surface of live HT-29 cells. These data provide additional evidence that the V3 loop is involved in the binding of gp120 to the GalCer receptor and show that multibranched V3 peptides are potent inhibitors of the GalCer-dependent pathway of HIV-1 infection in CD4-negative mucosal epithelial cells. PMID:7983725

  14. Immunodeficiency secondary to anti-cytokine autoantibodies

    PubMed Central

    Browne, Sarah K.; Holland, Steven M.

    2011-01-01

    Purpose of review Anti-cytokine autoantibodies are an important and emerging mechanism of disease pathogenesis. We will review the clinical and laboratory features of syndromes in which immunodeficiency is caused by or associated with neutralizing anti-cytokine autoantibodies. Recent findings A growing number of patients have been described who demonstrate unique infectious phenotypes associated with neutralizing autoantibodies that target a particular cytokine known to participate in host defense against the offending organism. Examples include anti-granulocyte macrophage-colony stimulating factor (GM-CSF) autoantibodies and pulmonary alveolar proteinosis; anti-interferon(IFN)-? autoantibodies and disseminated nontuberculous mycobacteria(NTM); anti-(interleukin)IL-6 autoantibodies and severe staphylococcal skin infection; anti-IL-17A, antiIL-17F or anti-IL-22 autoantibodies in patients with mucocutaneous candidiasis in the setting of both the autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED) syndrome and in cases of thymoma. Summary Anti-cytokine autoantibodies have manifestations that are diverse, ranging from asymptomatic to life-threatening. These emerging and fascinating causes of acquired immunodeficiency may explain some previously idiopathic syndromes. PMID:20966748

  15. AIDS: acquired immunodeficiency syndrome.

    PubMed Central

    Gilmore, N. J.; Beaulieu, R.; Steben, M.; Laverdière, M.

    1983-01-01

    Acquired immunodeficiency syndrome, or AIDS, is a new illness that occurs in previously healthy individuals. It is characterized by immunodeficiency, opportunistic infections and unusual malignant diseases. Life-threatening single or multiple infections with viruses, mycobacteria, fungi or protozoa are common. A rare neoplasm, Kaposi's sarcoma, has developed in approximately one third of patients with AIDS. More than 800 cases of AIDS have been reported in North America, over 24 of them in Canada. The majority of patients are male homosexuals, although AIDS has also developed in abusers of intravenously administered drugs, Haitian immigrants, individuals with hemophilia, recipients of blood transfusions, prostitutes, and infants, spouses and partners of patients with AIDS. The cause of AIDS is unknown, but the features are consistent with an infectious process. Early diagnosis can be difficult owing to the nonspecific symptoms and signs of the infections and malignant diseases. Therefore, vigilance by physicians is of utmost importance. PMID:6342737

  16. Primary immunodeficiencies: 2009 update

    PubMed Central

    Notarangelo, Luigi D.; Fischer, Alain; Geha, Raif. S.; Casanova, Jean-Laurent; Chapel, Helen; Conley, Mary Ellen; Cunningham-Rundles, Charlotte; Etzioni, Amos; Hammartröm, Lennart; Nonoyama, Shigeaki; Ochs, Hans D.; Puck, Jennifer; Roifman, Chaim; Seger, Reinhard; Wedgwood, Josiah

    2009-01-01

    More than 50 years after Ogdeon Bruton’s discovery of congenital agammaglobulinemia, human primary immunodeficiencies (PIDs) continue to unravel novel molecular and cellular mechanisms that govern development and function of the human immune system. This report provides the updated classification of PIDs, that has been compiled by the International Union of Immunological Societies (IUIS) Expert Committee of Primary Immunodeficiencies after its biannual meeting, in Dublin (Ireland) in June 2009. Since the appearance of the last classification in 2007, novel forms of PID have been discovered, and additional pathophysiology mechanisms that account for PID in humans have been unraveled. Careful analysis and prompt recognition of these disorders is essential to prompt effective forms of treatment and thus to improve survival and quality of life in patients affected with PIDs. PMID:20004777

  17. Human Immunodeficiency Virus

    Microsoft Academic Search

    Anita Patel; Michael Glick

    Oral health is an integral component of overall health and well-being in all patients. However, for an immunocompromised patient,\\u000a many common oral conditions may have a significant impact on quality of life. Intraoral pain, which is a common complaint\\u000a among patients with human immunodeficiency virus (HIV), will compromise patients’ ability to maintain adequate and appropriate\\u000a oral intake. Furthermore, the polypharmacopeia

  18. X-linked immunodeficiencies

    Microsoft Academic Search

    Hans D. Ochs; Luigi D. Notarangelo

    2004-01-01

    Recent advances in molecular genetics have allowed identification of at least seven genes involved in X-linked immunodeficiencies.\\u000a This has resulted not only in improved diagnostic possibilities but also in a better understanding of the pathophysiology\\u000a of these disorders. In some cases, mutations in the same gene have been shown to cause distinct clinical and immunologic phenotypes,\\u000a demonstrating a strong genotype-phenotype

  19. Two N-linked glycosylation sites in the V2 and C2 regions of human immunodeficiency virus type 1 CRF01_AE envelope glycoprotein gp120 regulate viral neutralization susceptibility to the human monoclonal antibody specific for the CD4 binding domain.

    PubMed

    Utachee, Piraporn; Nakamura, Shota; Isarangkura-Na-Ayuthaya, Panasda; Tokunaga, Kenzo; Sawanpanyalert, Pathom; Ikuta, Kazuyoshi; Auwanit, Wattana; Kameoka, Masanori

    2010-05-01

    A recombinant human monoclonal antibody, IgG1 b12 (b12), recognizes a conformational epitope on human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) gp120 that overlaps the CD4 binding domain. Although b12 is able to broadly neutralize HIV-1 subtype B, C, and D viruses, many HIV-1 CRF01_AE viruses are resistant to b12-mediated neutralization. In this report, we examined the molecular mechanisms underlying the low neutralization susceptibility of CRF01_AE viruses to b12, using recently established CRF01_AE Env recombinant viruses. Our results showed that two potential N-linked glycosylation (PNLG) sites in the V2 and C2 regions of Env gp120 played an important role in regulating the susceptibility of CRF01_AE Env to b12. The locations of these PNLG sites correspond to amino acid positions 186 and 197 in HXB2 Env gp120; thus, they are designated N186 and N197 in this study. Removal of N186 significantly conferred the b12 susceptibility of 2 resistant CRF01_AE Env clones, 65CC4 and 107CC2, while the introduction of N186 reduced the b12 susceptibility of a susceptible CRF01_AE Env clone, 65CC1. In addition, removal of both N186 and N197 conferred the b12 susceptibility of 3 resistant CRF01_AE Env clones, 45PB1, 62PL1, and 101PL1, whereas the removal of either N186 or N197 was not sufficient to confer the b12 susceptibility of these CRF01_AE Env clones. Finally, removal of N197 conferred the b12 susceptibility of 2 resistant CRF01_AE Env clones lacking N186, 55PL1 and 102CC2. Taken together, we propose that two PNLG sites, N186 and N197, in Env gp120 are important determinants of the b12 resistance of CRF01_AE viruses. PMID:20164234

  20. Two N-Linked Glycosylation Sites in the V2 and C2 Regions of Human Immunodeficiency Virus Type 1 CRF01_AE Envelope Glycoprotein gp120 Regulate Viral Neutralization Susceptibility to the Human Monoclonal Antibody Specific for the CD4 Binding Domain?

    PubMed Central

    Utachee, Piraporn; Nakamura, Shota; Isarangkura-na-ayuthaya, Panasda; Tokunaga, Kenzo; Sawanpanyalert, Pathom; Ikuta, Kazuyoshi; Auwanit, Wattana; Kameoka, Masanori

    2010-01-01

    A recombinant human monoclonal antibody, IgG1 b12 (b12), recognizes a conformational epitope on human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) gp120 that overlaps the CD4 binding domain. Although b12 is able to broadly neutralize HIV-1 subtype B, C, and D viruses, many HIV-1 CRF01_AE viruses are resistant to b12-mediated neutralization. In this report, we examined the molecular mechanisms underlying the low neutralization susceptibility of CRF01_AE viruses to b12, using recently established CRF01_AE Env recombinant viruses. Our results showed that two potential N-linked glycosylation (PNLG) sites in the V2 and C2 regions of Env gp120 played an important role in regulating the susceptibility of CRF01_AE Env to b12. The locations of these PNLG sites correspond to amino acid positions 186 and 197 in HXB2 Env gp120; thus, they are designated N186 and N197 in this study. Removal of N186 significantly conferred the b12 susceptibility of 2 resistant CRF01_AE Env clones, 65CC4 and 107CC2, while the introduction of N186 reduced the b12 susceptibility of a susceptible CRF01_AE Env clone, 65CC1. In addition, removal of both N186 and N197 conferred the b12 susceptibility of 3 resistant CRF01_AE Env clones, 45PB1, 62PL1, and 101PL1, whereas the removal of either N186 or N197 was not sufficient to confer the b12 susceptibility of these CRF01_AE Env clones. Finally, removal of N197 conferred the b12 susceptibility of 2 resistant CRF01_AE Env clones lacking N186, 55PL1 and 102CC2. Taken together, we propose that two PNLG sites, N186 and N197, in Env gp120 are important determinants of the b12 resistance of CRF01_AE viruses. PMID:20164234

  1. Efficient Neutralization of Primary Isolates of HIV1 by a Recombinant Human Monoclonal Antibody

    Microsoft Academic Search

    Dennis R. Burton; Jayashree Pyati; Raju Koduri; Stephen J. Sharp; George B. Thornton; Paul W. H. I. Parren; Lynette S. W. Sawyer; R. Michael Hendry; Nancy Dunlop; Peter L. Nara; Michael Lamacchia; Eileen Garratty; E. Richard Stiehm; Yvonne J. Bryson; Yunzhen Cao; John P. Moore; David D. Ho; Carlos F. Barbas III

    1994-01-01

    The ability of antibodies to neutralize diverse primary isolates of human immunodeficiency virus-type 1 in vitro has been questioned, with implications for the likely efficacy of vaccines. A recombinant human antibody to envelope glycoprotein gp120 was generated and used to show that primary isolates are not refractory to antibody neutralization. The recombinant antibody neutralized more than 75 percent of the

  2. Space Flight Immunodeficiency

    NASA Technical Reports Server (NTRS)

    Shearer, William T.

    1999-01-01

    The National Aeronautics and Space Administration (NASA) has had sufficient concern for the well-being of astronauts traveling in space to create the National Space Biomedical Research Institute (NSBRI), which is investigating several areas of biomedical research including those of immunology. As part of the Immunology, Infection, and Hematology Team, the co-investigators of the Space Flight Immunodeficiency Project began their research projects on April 1, 1998 and are now just into the second year of work. Two areas of research have been targeted: 1) specific immune (especially antibody) responses and 2) non-specific inflammation and adhesion. More precise knowledge of these two areas of research will help elucidate the potential harmful effects of space travel on the immune system, possibly sufficient to create a secondary state of immunodeficiency in astronauts. The results of these experiments are likely to lead to the delineation of functional alterations in antigen presentation, specific immune memory, cytokine regulation of immune responses, cell to cell interactions, and cell to endothelium interactions.

  3. 78 FR 29755 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-21

    ...FDA-2013-N-0473] Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency...on human immunodeficiency virus (HIV) Patient-Focused Drug Development and HIV Cure Research. Patient-Focused Drug Development is part of...

  4. 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

  5. Testing for Human Immunodeficiency Virus

    MedlinePLUS

    ... screening test looks for the presence of HIV antibodies in a sample of your blood. Urine and ... damaged by infection with human immunodeficiency virus (HIV). Antibodies: Proteins in the blood produced in reaction to ...

  6. Inhibition of gallium-67 uptake in melanoma by an anti-human transferrin receptor monoclonal antibody

    SciTech Connect

    Chan, S.M.; Hoffer, P.B.; Maric, N.; Duray, P.

    1987-08-01

    The effect of an anti-human transferrin receptor (anti-TFR) monoclonal antibody (MoAb), designated B3/25, and an anti-melanoma antibody, designated 96.5, on the uptake of gallium-67 (/sup 67/Ga) by tumor was studied. Three groups of six athymic mice bearing a human melanoma were injected via tail vein with (a) 0.55 mg human serum albumin (HSA) (control group), (b) 0.5 mg MoAb B3/25 + 0.55 mg HSA, and (c) 0.5 mg MoAb 96.5 + 0.55 mg HSA, respectively. Twenty-four hours later, each mouse was given an intravenous dose of 5 microCi (/sup 67/Ga) citrate. Biodistribution of activity (percent injected dose per gram) determined 48 hr after injection of /sup 67/Ga showed a 75% decrease in tumor uptake in the group of mice that received B3/25 (anti-TFR MoAb) compared with the control group. In contrast, MoAb 96.5 did not show any effect on melanoma uptake of /sup 67/Ga. Histologic findings suggest that the decreased uptake was not due to cellular damage resulting from binding of B3/25 to TFR. The results of this study strongly suggest the involvement of TFR in the in vivo tumor uptake of /sup 67/Ga.

  7. An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

    PubMed Central

    Traub, Stephanie; Nikonova, Alexandra; Carruthers, Alan; Dunmore, Rebecca; Vousden, Katherine A.; Gogsadze, Leila; Hao, Weidong; Zhu, Qing; Bernard, Katie; Zhu, Jie; Dymond, Michael; McLean, Gary R.; Walton, Ross P.; Glanville, Nicholas; Humbles, Alison; Khaitov, Musa; Wells, Ted; Kolbeck, Roland; Leishman, Andrew J.; Sleeman, Matthew A.

    2013-01-01

    Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ?90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo. PMID:23935498

  8. Anti-AIDS Agents 78 †. Design, Synthesis, Metabolic Stability Assessment, and Antiviral Evaluation of Novel Betulinic Acid Derivatives as Potent Anti-Human Immunodeficiency Virus (HIV) Agents

    PubMed Central

    Qian, Keduo; Yu, Donglei; Chen, Chin-Ho; Huang, Li; Morris-Natschke, Susan L.; Nitz, Theodore J.; Salzwedel, Karl; Reddick, Mary; Allaway, Graham P.; Lee, Kuo-Hsiung

    2009-01-01

    In a continuing study of potent anti-HIV agents, seventeen 28,30-disubstituted betulinic acid (BA, 1) derivatives, as well as seven novel 3,28-disubstituted BA analogs were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, compound 21 showed an improved solubility and equal anti-HIV potency (EC50: 0.09 ?M), when compared to HIV entry inhibitors 3b (IC9564) and 4 (A43-D). Using a cyclic secondary amine to form the C-28 amide bond increased the metabolic stability of the derivatives significantly in pooled human liver microsomes. The most potent compounds 47 and 48 displayed potent anti-HIV activity with EC50 values of 0.007 ?M and 0.006 ?M, respectively. These results are slightly better than that of bevirimat (2), which is currently in Phase IIb clinical trials. Compounds 47 and 48 should serve as attractive promising leads to develop next generation, metabolically stable, 3,28-disubstituted bifunctional HIV-1 inhibitors as clinical trials candidates. PMID:19388685

  9. 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

  10. Screening for Human Immunodeficiency Virus (HIV)

    MedlinePLUS

    ... Understanding Task Force Recommendations Screening for Human Immunodeficiency Virus (HIV) The U.S. Preventive Services Task Force (Task ... is human immunodeficiency virus (HIV)? HIV is a virus that attacks cells that help the body fight ...

  11. 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

  12. Actin cytoskeletal defects in immunodeficiency

    PubMed Central

    Moulding, Dale A; Record, Julien; Malinova, Dessislava; Thrasher, Adrian J

    2013-01-01

    The importance of the cytoskeleton in mounting a successful immune response is evident from the wide range of defects that occur in actin-related primary immunodeficiencies (PIDs). Studies of these PIDs have revealed a pivotal role for the actin cytoskeleton in almost all stages of immune system function, from hematopoiesis and immune cell development, through to recruitment, migration, intercellular and intracellular signaling, and activation of both innate and adaptive immune responses. The major focus of this review is the immune defects that result from mutations in the Wiskott-Aldrich syndrome gene (WAS), which have a broad impact on many different processes and give rise to clinically heterogeneous immunodeficiencies. We also discuss other related genetic defects and the possibility of identifying new genetic causes of cytoskeletal immunodeficiency. PMID:24117828

  13. Update on the treatment of primary immunodeficiencies

    Microsoft Academic Search

    J. M. García; T. Español; C. Casas C

    2007-01-01

    A general review of advances in the treatment of Primary Immunodeficiencies (PID) has been performed.Treatment with immunoglobulins is indicated in cases of humoral immunodeficiencies and in selected cases of combined immunodeficiencies.The use of intramuscular immunoglobulins in the treatment of PID was abandoned after obtaining the intravenous immunoglobulins, since these are much more effective and have fewer adverse effects. Now subcutaneous

  14. Cross-reactivity of anti-human cytokine monoclonal antibodies used as a tool to identify novel immunological biomarkers in domestic ruminants.

    PubMed

    Dorneles, E M S; Araújo, M S S; Teixeira-Carvalho, A; Martins-Filho, O A; Lage, A P

    2015-01-01

    Eleven commercially available PE-labeled anti-human (IL-1-?, IL-6, IL-8, TNF-?, IL-17A, IL-5, IL-10, IL-12 and IL-13) and anti-mouse (IL-10, TNF-?) cytokine monoclonal antibodies (mAbs) were tested for cross-reactivity with cattle, goat, and sheep cytokines. Cross-reactivity was assessed by comparative analysis with the standard reactivity of the target species. Our data demonstrated that anti-human IL-1-?, IL-6, IL-8, IL-17A and IL-10 mAbs cross-react with all ruminant species tested. Anti-human IL-5 mAb showed a strong cross-reactivity with cattle and goat IL-5, while anti-human TNF-? mAb showed a selective cross-reactivity with goat TNF-?. No cross-reactivity with the ruminant cytokines was observed for anti-human IL-12 and IL-13 mAbs or for the two anti-mouse cytokine mAbs tested. The present study demonstrated the cross-reactivity of various anti-human cytokine mAbs with cattle, sheep, and goat cytokines, increasing the range of immunological biomarkers for studies in veterinary medicine. PMID:25730032

  15. Primary immunodeficiencies underlying fungal infections

    PubMed Central

    Lanternier, Fanny; Cypowyj, Sophie; Picard, Capucine; Bustamante, Jacinta; Lortholary, Olivier; Casanova, Jean-Laurent; Puel, Anne

    2014-01-01

    Purpose of review We review the primary immunodeficiencies underlying an increasing variety of superficial and invasive fungal infections. We also stress that the occurrence of such fungal infections should lead physicians to search for the corresponding single-gene inborn errors of immunity. Finally, we suggest that other fungal infections may also result from hitherto unknown inborn errors of immunity, at least in some patients with no known risk factors. Recent findings An increasing number of primary immunodeficiencies are being shown to underlie fungal infectious diseases in children and young adults. Inborn errors of the phagocyte NADPH oxidase complex (chronic granulomatous disease), severe congenital neutropenia and leukocyte adhesion deficiency type I confer a predisposition to invasive aspergillosis and candidiasis. More rarely, inborn errors of IFN-? immunity underlie endemic mycoses. Inborn errors of IL-17 immunity have recently been shown to underlie chronic mucocutaneous candidiasis, whereas inborn errors of CARD9 immunity underlie deep dermatophytosis and invasive candidiasis. Summary Chronic mucocutaneous candidiasis, invasive candidiasis, invasive aspergillosis, deep dermatophytosis, pneumocystosis, and endemic mycoses can all be caused by primary immunodeficiencies. Each type of infection is highly suggestive of a specific type of primary immunodeficiency. In the absence of overt risk factors, single-gene inborn errors of immunity should be sought in children and young adults with these and other fungal diseases. PMID:24240293

  16. 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

  17. A quadrivalent HPV vaccine induces humoral and cellular immune responses in WHIM immunodeficiency syndrome.

    PubMed

    Handisurya, Alessandra; Schellenbacher, Christina; Reininger, Bärbel; Koszik, Frieder; Vyhnanek, Philipp; Heitger, Andreas; Kirnbauer, Reinhard; Förster-Waldl, Elisabeth

    2010-07-01

    WHIM-syndrome is an inherited immunodeficiency disorder with abnormal susceptibility to human papillomavirus (HPV) infection and diseases. We determined safety and immunogenicity to a quadrivalent HPV vaccine in WHIM-syndrome by detection of HPV-specific antibodies and lymphoproliferation. In virus-like-particle (VLP)-ELISA, a WHIM patient showed antibody titers up to 400 for HPV-6/11/16/18, whereas immuno-competent controls developed titers of 6400-25,600. In pseudovirion assays, the patient's neutralization titers ranged from 20 to 400 to the four HPV vaccine types, while titers of 1600-25,600 were detected in healthy vaccinees. Specific proliferation of PBMC of the WHIM patient to the HPV vaccine was demonstrated. This first report on response to HPV vaccination in WHIM-immunodeficiency highlights that patients with WHIM-syndrome, and probably other immunodeficiencies, may benefit from HPV immunoprophylaxis. PMID:20472031

  18. The role of feline syncytium forming virus in feline immunodeficiency virus-mediated acquired immunodeficiency

    E-print Network

    Zenger, Elizabeth

    1991-01-01

    of the requirements for the degree of MASTER OF SCIENCE December 1991 Major Subject: Veterinary Medicine and Surgery THE ROLE OF FELINE SYNCYTIUM FORMING VIRUS IN FELINE IMMUNODEFICIENCY VIRUS-MEDIATED ACQUIRED IMMUNODEFICIENCY A Thesis by ELIZABETH ZENGER...

  19. Evolution of a Simian Immunodeficiency Virus Pathogen

    PubMed Central

    Edmonson, Paul; Murphey-Corb, Michael; Martin, Louis N.; Delahunty, Claire; Heeney, Jonathan; Kornfeld, Hardy; Donahue, Peter R.; Learn, Gerald H.; Hood, Leroy; Mullins, James I.

    1998-01-01

    Analysis of disease induction by simian immunodeficiency viruses (SIV) in macaques was initially hampered by a lack of molecularly defined pathogenic strains. The first molecularly cloned SIV strains inoculated into macaques, SIVmacBK28 and SIVmacBK44 (hereafter designated BK28 and BK44, respectively), were cases in point, since they failed to induce disease within 1 year postinoculation in any inoculated animal. Here we report the natural history of infection with BK28 and BK44 in inoculated rhesus macaques and efforts to increase the pathogenicity of BK28 through genetic manipulation and in vivo passage. BK44 infection resulted in no disease in four animals infected for more than 7 years, whereas BK28 induced disease in less than half of animals monitored for up to 7 years. Elongation of the BK28 transmembrane protein (TM) coding sequence truncated by prior passage in human cells marginally increased pathogenicity, with two of four animals dying in the third year and one dying in the seventh year of infection. Modification of the BK28 long terminal repeat to include four consensus nuclear factor SP1 and two consensus NF-?B binding sites enhanced early virus replication without augmenting pathogenicity. In contrast, in vivo passage of BK28 from the first animal to die from immunodeficiency disease (1.5 years after infection) resulted in a consistently pathogenic strain and a 50% survival time of about 1.3 years, thus corresponding to one of the most pathogenic SIV strains identified to date. To determine whether the diverse viral quasispecies that evolved during in vivo passage was required for pathogenicity or whether a more virulent virus variant had evolved, we generated a molecular clone composed of the 3? half of the viral genome derived from the in vivo-passaged virus (H824) fused with the 5? half of the BK28 genome. Kinetics of disease induction with this cloned virus (BK28/H824) were similar to those with the in vivo-passaged virus, with four of five animals surviving less than 1.7 years. Thus, evolution of variants with enhanced pathogenicity can account for the increased pathogenicity of this SIV strain. The genetic changes responsible for this virulent transformation included at most 59 point mutations and 3 length-change mutations. The critical mutations were likely to have been multiple and dispersed, including elongation of the TM and Nef coding sequences; changes in RNA splice donor and acceptor sites, TATA box sites, and Sp1 sites; multiple changes in the V2 region of SU, including a consensus neutralization epitope; and five new N-linked glycosylation sites in SU. PMID:9420239

  20. Growth hormone deficiency and combined immunodeficiency.

    PubMed Central

    Tang, M L; Kemp, A S

    1993-01-01

    The first description of an association of isolated growth hormone deficiency (IGHD) and combined immunodeficiency is presented. The findings suggest that IGHD should be considered as a cause of short stature in children with combined immunodeficiency before attributing growth retardation to infection. PMID:8481046

  1. Human Immunodeficiency Virus (HIV) Primary Infection

    MedlinePLUS

    newsletter | contact Share | Human Immunodeficiency Virus (HIV) Primary Infection Information for adults A A A When HIV is first contracted, there may be ... 1–6 weeks following exposure to HIV (the human immunodeficiency virus). Chronic infection with this virus can ...

  2. Evolutionarily Conserved Epitopes on Human Immunodeficiency Virus Type 1 (HIV-1) and Feline Immunodeficiency Virus Reverse Transcriptases Detected by HIV-1-Infected Subjects

    PubMed Central

    Sanou, Missa P.; Roff, Shannon R.; Mennella, Antony; Sleasman, John W.; Rathore, Mobeen H.; Levy, Jay A.

    2013-01-01

    Anti-human immunodeficiency virus (HIV) cytotoxic T lymphocyte (CTL)-associated epitopes, evolutionarily conserved on both HIV type 1 (HIV-1) and feline immunodeficiency virus (FIV) reverse transcriptases (RT), were identified using gamma interferon (IFN-?) enzyme-linked immunosorbent spot (ELISpot) and carboxyfluorescein diacetate succinimide ester (CFSE) proliferation assays followed by CTL-associated cytotoxin analysis. The peripheral blood mononuclear cells (PBMC) or T cells from HIV-1-seropositive (HIV+) subjects were stimulated with overlapping RT peptide pools. The PBMC from the HIV+ subjects had more robust IFN-? responses to the HIV-1 peptide pools than to the FIV peptide pools, except for peptide-pool F3. In contrast, much higher and more frequent CD8+ T-cell proliferation responses were observed with the FIV peptide pools than with the HIV peptide pools. HIV-1-seronegative subjects had no proliferation or IFN-? responses to the HIV and FIV peptide pools. A total of 24% (40 of 166) of the IFN-? responses to HIV pools and 43% (23 of 53) of the CD8+ T-cell proliferation responses also correlated to responses to their counterpart FIV pools. Thus, more evolutionarily conserved functional epitopes were identified by T-cell proliferation than by IFN-? responses. In the HIV+ subjects, peptide-pool F3, but not the HIV H3 counterpart, induced the most IFN-? and proliferation responses. These reactions to peptide-pool F3 were highly reproducible and persisted over the 1 to 2 years of testing. All five individual peptides and epitopes of peptide-pool F3 induced IFN-? and/or proliferation responses in addition to inducing CTL-associated cytotoxin responses (perforin, granzyme A, granzyme B). The epitopes inducing polyfunctional T-cell activities were highly conserved among human, simian, feline, and ungulate lentiviruses, which indicated that these epitopes are evolutionarily conserved. These results suggest that FIV peptides could be used in an HIV-1 vaccine. PMID:23824804

  3. Immunotherapy for primary immunodeficiency diseases.

    PubMed

    Wood, Philip

    2012-05-01

    The 2 most commonly encountered primary immunodeficiency syndromes in adult practice are antibody deficiency disorders and hereditary angioedema.Immunologic therapy for these disorders has significantly improved patient management. Therapy with immunoglobulin leads to improvement in overall quality of life. With increasing survival rates and decreasing levels of life-threatening infections in patients with primary antibody deficiencies, disease complications are more commonly encountered. Treatment of these complications with monoclonal antibody therapy seems promising and is likely to increase in the future. More recently,several additional agents have become available, including novel drugs targeted at different elements of the disease process. PMID:22703850

  4. 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

  5. Common variable immunodeficiency - an update

    PubMed Central

    2012-01-01

    Common variable immunodeficiency (CVID) describes a heterogeneous subset of hypogammaglobulinemias of unknown etiology. Typically, patients present with recurrent bacterial infections of the respiratory and gastrointestinal tract. A significant proportion of CVID patients develops additional autoimmune, inflammatory or lymphoproliferative complications. CVID is the most frequent symptomatic primary immunodeficiency encountered in adults. Informative monogenetic defects have been found in single patients and families but in most cases the pathogenesis is still elusive. Numerous immunological studies have demonstrated phenotypic and functional abnormalities of T cells, B cells and antigen-presenting cells. A hallmark is the impaired memory B-cell formation that has been taken advantage of for classifying CVID patients. Clinical multi-center studies have demonstrated a correlation between immunological markers and clinical presentation. Long-term outcome is significantly influenced by delay of diagnosis and treatment and the presence of chronic inflammatory complications. While immunoglobulin replacement therapy plus antibiotics can control infections in most cases, patients with non-infectious inflammatory complications such as granulomatous inflammation, interstitial lung disease, inflammatory bowel disease, lymphoproliferation and developing malignancies still represent a therapeutic challenge. In this review we provide a systematic overview of the immunological, clinical, diagnostic and therapeutic aspects of CVID and highlight recent developments in these fields. PMID:23043756

  6. Establishment of monoclonal anti-human CD26 antibodies suitable for immunostaining of formalin-fixed tissue

    PubMed Central

    2014-01-01

    Background A T cell costimulatory molecule with dipeptidyl peptidase IV (DPPIV) activity in its extracellular region, CD26 is a multifunctional molecule associated with various proteins such as adenosine deaminase, caveolin-1, CXCR4, collagen, and fibronectin, while playing an important role in the regulation of inflammatory responses and tumor biology. We have focused on CD26 as a novel therapeutic target for various tumors and immune disorders, and have developed a humanized anti-CD26 monoclonal antibody (mAb), YS110, which is currently being evaluated in a phase I clinical trial for patients with CD26-expressing tumors, including malignant mesothelioma. Since detection of tumor CD26 expression is required for determining potential eligibility for YS110 therapy, the development of anti-human CD26 mAb that can clearly and reliably detect the denatured CD26 molecule in the formalin-fixed paraffin-embedded tissues is critical. Methods To develop novel anti-CD26 mAbs capable of binding to the denatured CD26, we immunized mice with CD26 protein denatured in urea buffer. After the fusion of splenocytes and myeloma cells, the mAbs were screened for specific reactivity with human CD26 by flow cytometry, enzyme-linked immunosorbent assay, and immunohistochemistry. The binding competitiveness of novel anti-CD26 mAbs with the humanized anti-CD26 mAb YS110 was also examined. Results We have succeeded in developing novel anti-human CD26 mAbs suitable for immunohistochemical staining of CD26 in formalin-fixed tissue sections with reliable clarity and intensity. Importantly, some of these mAbs exhibit no cross-reactivity with the humanized anti-CD26 mAb. Conclusions These novel mAbs are potentially useful as companion diagnostic agents to analyze CD26 expression in the clinical setting while advancing future CD26-related research. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5987140221097729 PMID:24502396

  7. Anti-human protein S antibody induces tissue factor expression through a direct interaction with platelet phosphofructokinase

    PubMed Central

    Chen, Changyi; Liao, Dan; Wang, Jing; Liang, Zhengdong; Yao, Qizhi

    2013-01-01

    Introduction Autoantibodies including anti-human protein S antibody (anti-hPS Ab) and anti-human protein C antibody (anti-hPC Ab) can be detected in patients with autoimmune diseases with hypercoagulability. The objective of the present study was to determine the effects and molecular pathways of these autoantibodies on tissue factor (TF) expression in human coronary artery endothelial cells (HCAECs). Materials and Methods HCAECs were treated with anti-hPS Ab or anti-hPC Ab for 3 hours. TF expression was measured by real-time PCR and Western blot. TF-mediated procoagulant activity was determined by a commercial kit. MAPK phosphorylation was analyzed by Bio-Plex luminex immunoassay and Western blot. The potential proteins interacting with anti-hPS Ab were studied by immunoprecipitation, mass spectrometry and in vitro pull-down assay. Results Anti-hPS Ab, but not anti-hPC Ab, specifically induced TF expression and TF-mediated procoagulant activity in HCAECs in a concentration-dependent manner. This effect was confirmed in human umbilical endothelial cells (HUVECs). ERK1/2 phosphorylation was induced by anti-hPS Ab treatment, while inhibition of ERK1/2 by U0216 partially blocked anti-hPS Ab-induced TF upregulation (P<0.05). In addition, anti-hPS Ab specifically cross-interacted with platelet phosphofructokinase (PFKP) in HCAECs. Anti-hPS Ab was able to directly inhibit PFKP activities in HCAECs. Furthermore, silencing of PFKP by PFKP shRNA resulted in TF upregulation in HCAECs, while activation of PFKP by fructose-6-phosphate partially blocked the effect of anti-hPS Ab on TF upregulation (P<0.05). Conclusions Anti-hPS Ab induces TF expression through a direct interaction with PFKP and ERK1/2 activation in HCAECs. Anti-hPS Ab may directly contribute to vascular thrombosis in the patient with autoimmune disorders. PMID:24331211

  8. Current Perspectives on Primary Immunodeficiency Diseases

    PubMed Central

    Kumar, Arvind; Teuber, Suzanne S.; Gershwin, M. Eric

    2006-01-01

    Since the original description of X-linked agammaglobulinemia in 1952, the number of independent primary immunodeficiency diseases (PIDs) has expanded to more than 100 entities. By definition, a PID is a genetically determined disorder resulting in enhanced susceptibility to infectious disease. Despite the heritable nature of these diseases, some PIDs are clinically manifested only after prerequisite environmental exposures but they often have associated malignant, allergic, or autoimmune manifestations. PIDs must be distinguished from secondary or acquired immunodeficiencies, which are far more common. In this review, we will place these immunodeficiencies in the context of both clinical and laboratory presentations as well as highlight the known genetic basis. PMID:17162365

  9. Strategies for B-Cell Receptor Repertoire Analysis in Primary Immunodeficiencies: From Severe Combined Immunodeficiency to Common Variable Immunodeficiency

    PubMed Central

    IJspeert, Hanna; Wentink, Marjolein; van Zessen, David; Driessen, Gertjan J.; Dalm, Virgil A. S. H.; van Hagen, Martin P.; Pico-Knijnenburg, Ingrid; Simons, Erik J.; van Dongen, Jacques J. M.; Stubbs, Andrew P.; van der Burg, Mirjam

    2015-01-01

    The antigen receptor repertoires of B- and T-cells form the basis of the adaptive immune response. The repertoires should be sufficiently diverse to recognize all possible pathogens. However, careful selection is needed to prevent responses to self or harmless antigens. Limited antigen receptor repertoire diversity leads to immunodeficiency, whereas unselected or misdirected repertoires can result in autoimmunity. The antigen receptor repertoire harbors information about abnormalities in many immunological disorders. Recent developments in next generation sequencing allow the analysis of the antigen receptor repertoire in much greater detail than ever before. Analyzing the antigen receptor repertoire in patients with mutations in genes responsible for the generation of the antigen receptor repertoire will give new insights into repertoire formation and selection. In this perspective, we describe strategies and considerations for analysis of the naive and antigen-selected B-cell repertoires in primary immunodeficiency patients with a focus on severe combined immunodeficiency and common variable immunodeficiency.

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... false Human immunodeficiency virus (HIV) âlookbackâ requirements. 610.46...610.46 Human immunodeficiency virus (HIV) “lookback” requirements. ...evidence of human immunodeficiency virus (HIV) infection when tested under §...

  11. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... false Human immunodeficiency virus (HIV) âlookbackâ requirements. 610.46...610.46 Human immunodeficiency virus (HIV) “lookback” requirements. ...evidence of human immunodeficiency virus (HIV) infection when tested under §...

  12. 75 FR 51273 - Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected Populations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-19

    ...Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected...Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected...Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately...

  13. Neutral beam injector

    SciTech Connect

    Hashimoto, K.

    1984-10-30

    A neutral beam injector comprising a neutralizing cell for neutralizing charged particles, and a direct converter for recovering the energy of unneutralized charged particles passed through the neutralizing cell. The direct converter comprises a collector for collecting charged particles, a deflector which is interposed between the neutralizing cell and the collector in order to cross and diverge beams of the charged particles, a first electron suppressor interposed between the neutralizing cell and the deflector, and a second electron suppressor disposed behind the collector.

  14. Use of Human Immunodeficiency Virus Nucleoside-Analog Reverse Transcriptase Inhibitors to Control Human Immunodeficiency Virus

    NSDL National Science Digital Library

    American Society For Microbiology

    2005-03-11

    This animation illustrates how human immunodeficiency virus (HIV) nucleoside-analog reverse transcriptase inhibitors (zidovudine, didanosine, zalcitabine, stavudine, lamivudine, and abacavir) inhibit replication of the HIV.

  15. Laboratory diagnosis of primary immunodeficiencies.

    PubMed

    Locke, Bradley A; Dasu, Trivikram; Verbsky, James W

    2014-04-01

    Primary immune deficiency disorders represent a highly heterogeneous group of disorders with an increased propensity to infections and other immune complications. A careful history to delineate the pattern of infectious organisms and other complications is important to guide the workup of these patients, but a focused laboratory evaluation is essential to the diagnosis of an underlying primary immunodeficiency. Initial workup of suspected immune deficiencies should include complete blood counts and serologic tests of immunoglobulin levels, vaccine titers, and complement levels, but these tests are often insufficient to make a diagnosis. Recent advancements in the understanding of the immune system have led to the development of novel immunologic assays to aid in the diagnosis of these disorders. Classically utilized to enumerate lymphocyte subsets, flow cytometric-based assays are increasingly utilized to test immune cell function (e.g., neutrophil oxidative burst, NK cytotoxicity), intracellular cytokine production (e.g., TH17 production), cellular signaling pathways (e.g., phosphor-STAT analysis), and protein expression (e.g., BTK, Foxp3). Genetic testing has similarly expanded greatly as more primary immune deficiencies are defined, and the use of mass sequencing technologies is leading to the identification of novel disorders. In order to utilize these complex assays in clinical care, one must have a firm understanding of the immunologic assay, how the results are interpreted, pitfalls in the assays, and how the test affects treatment decisions. This article will provide a systematic approach of the evaluation of a suspected primary immunodeficiency, as well as provide a comprehensive list of testing options and their results in the context of various disease processes. PMID:24569953

  16. Two novel inhibitory anti-human factor XI antibodies prevent cessation of blood flow in a murine venous thrombosis model.

    PubMed

    van Montfoort, M L; Knaup, V L; Marquart, J A; Bakhtiari, K; Castellino, F J; Hack, C E; Meijers, J C M

    2013-11-01

    Coagulation factor XI (FXI) is a promising target for anticoagulation, because of its major role in thrombosis and relatively minor role in haemostasis. This implies that inhibition of FXI can prevent thrombosis without causing bleeding. It was our aim to investigate the antithrombotic properties of two novel inhibitory anti-human FXI antibodies (?FXI-175 and ?FXI-203). The in vitro properties of both antibodies were analysed using standard clotting assays and calibrated automated thrombography. For the in vivo model we used FXI knockout mice, in which FXI plasma levels were restored with purified human FXI. Thrombosis was induced by applying ferric chloride to the vena cava inferior, after which time to occlusion was analysed. A tail bleeding assay was used to investigate the safety of both antibodies. Using calibrated automated thrombography, both antibodies inhibited thrombin generation initiated via the intrinsic pathway. In contrast, upon tissue factor (TF)-initiated thrombin generation, ?FXI-203 did not inhibit thrombin generation, while ?FXI-175 inhibited thrombin generation only at low concentrations of TF. In the murine thrombosis model, the vena cava inferior remained patent for 25 minutes (min) in mice treated with ?FXI-175 and for 12.5 min in ?FXI-203 treated animals, which was significantly longer than in placebo-treated animals (5 min, p<0.05). Neither antibody caused severe blood loss in a tail bleeding assay. In conclusion, the two inhibitory antibodies against FXI prevented cessation of blood flow in a murine thrombosis model without inducing a bleeding tendency. PMID:23925504

  17. Antiretroviral spermicide WHI-07 prevents vaginal and rectal transmission of feline immunodeficiency virus in domestic cats.

    PubMed

    D'Cruz, Osmond J; Waurzyniak, Barbara; Uckun, Fatih M

    2004-04-01

    WHI-07 [5-bromo-6-methoxy-5,6-dihydro-3'-azidothymidine-5'-(p-bromophenyl)-methoxy alaninyl phosphate] is a novel dual-function aryl phosphate derivative of zidovudine with potent anti-human immunodeficiency virus (HIV) and spermicidal activities. WHI-07 was active against the feline immunodeficiency virus (FIV). This study evaluated whether topical application of WHI-07 as a single agent and in combination with an organometallic vanadium complex, vanadocene dithiocarbamate (VDDTC), via a nontoxic gel microemulsion can block vaginal as well as rectal transmission of feline AIDS (FAIDS) by chronically FIV-infected feline T cells in the natural host model. Genital transmission of FIV was monitored in recipient cats by the appearance of viral antibodies to FIV Gag proteins and by virus isolation of blood leukocytes as measured by FIV reverse transcriptase activity and FIV-specific PCR. Microbicidal activity was considered effective when the treated cats did not show evidence of FIV infection for up to 18 weeks postchallenge. An aggregate analysis of 46 specific-pathogen-free cats revealed that a single dose of the infected cell inoculum efficiently transmitted FIV infection when delivered into the vagina (100%) or rectum (66%). Pretreatment of the vagina or rectum with 2% WHI-07 alone or in combination with 0.25% VDDTC significantly (P = 0.004) protected cats from genital transmission by the highly infectious inoculum (7 million FIV(Bangston)-infected feline T cells). Collectively, using the vaginal and rectal transmucosal model for FAIDS, our studies demonstrated that WHI-07 either alone or in combination with a vanadocene has clinical potential for the development of a dual-function anti-HIV microbicide for sexually active women. PMID:15047505

  18. Cell surface effects of human immunodeficiency virus

    Microsoft Academic Search

    Robert F. Garry; A. Arthur Gottlieb; Kenneth P. Zuckerman; John R. Pace; Thomas W. Frank; Denise A. Bostick

    1988-01-01

    Cell killing by human immunodeficiency virus (HIV) is thought to contribute to many of the defects of the acquired immunodeficiency syndrome (AIDS). Two types of cytopathology are observed in HIV-infected cultured cells: cell-cell fusion and killing of single cells. Both killing processes appear to involve cell surface effects of HIV. A model is proposed for the HIV-mediated cell surface processes

  19. Hematologic Manifestations of Feline Immunodeficiency Virus Infection

    Microsoft Academic Search

    Grady H. Shelton; Michael L. Linenberger; Chris K. Grant; Janis L. Abkowitz

    Studies were done on 53 cats with community-acquired infection with the feline immunodeficiency virus (FIV) to determine if hematologic abnormalities were comparable with those observed in patients seropositive for the human immunodeficiency virus (HIV). Nine cats were asymptom- atic, 24 had clinical symptoms equivalent to AIDS-related complex (ARC), and 20 had AIDS-like disease. Hematologic abnormalities were detected in 75% (40

  20. History of Primary Immunodeficiency Diseases in Iran

    PubMed Central

    Aghamohammadi, Asghar; Moin, Mostafa; Rezaei, Nima

    2010-01-01

    Pediatric immunology came into sight in the second half of 20th century, when pediatricians and basic immunologists began to give attention to diagnosis and treatment of children with primary immunodeficiency diseases (PIDs). Understanding the genetic and mechanistic basis of PIDs provides unique insight into the functioning of the immune system. By progress in basic and clinical immunology, many infrastructural organizations and academic centers have been established in many countries worldwide to focus on training and research on the immune system and related disorders. Along with progress in basic and clinical immunology in the world, pediatric immunology had a good progress in Iran during the last 33-year period. Now, patients with PIDs can benefit from multidisciplinary comprehensive care, which is provided by clinical immunologists in collaboration with other specialists. Patients with history of recurrent and/or chronic infections suggestive of PIDs are evaluated by standard and research-based testing and receive appropriate treatment. The progress in PIDs can be described in three periods. Development of training program for clinical fellowship in allergy and immunology, multidisciplinary and international collaborative projects, primary immunodeficiency diseases textbooks, meetings on immunodeficiency disorders, improvement in diagnosis and treatment, and construction of Iranian primary immunodeficiency association, Students' research group for immunodeficiencies, Iranian primary immunodeficiency registry, and the immunological societies and centers were the main activities on PIDs during these years. In this article, we review the growth of modern pediatric immunology and PIDs status in Iran. PMID:23056678

  1. Delineating antibody recognition in polyclonal sera from patterns of HIV-1 isolate neutralization.

    PubMed

    Georgiev, Ivelin S; Doria-Rose, Nicole A; Zhou, Tongqing; Kwon, Young Do; Staupe, Ryan P; Moquin, Stephanie; Chuang, Gwo-Yu; Louder, Mark K; Schmidt, Stephen D; Altae-Tran, Han R; Bailer, Robert T; McKee, Krisha; Nason, Martha; O'Dell, Sijy; Ofek, Gilad; Pancera, Marie; Srivatsan, Sanjay; Shapiro, Lawrence; Connors, Mark; Migueles, Stephen A; Morris, Lynn; Nishimura, Yoshiaki; Martin, Malcolm A; Mascola, John R; Kwong, Peter D

    2013-05-10

    Serum characterization and antibody isolation are transforming our understanding of the humoral immune response to viral infection. Here, we show that epitope specificities of HIV-1-neutralizing antibodies in serum can be elucidated from the serum pattern of neutralization against a diverse panel of HIV-1 isolates. We determined "neutralization fingerprints" for 30 neutralizing antibodies on a panel of 34 diverse HIV-1 strains and showed that similarity in neutralization fingerprint correlated with similarity in epitope. We used these fingerprints to delineate specificities of polyclonal sera from 24 HIV-1-infected donors and a chimeric siman-human immunodeficiency virus-infected macaque. Delineated specificities matched published specificities and were further confirmed by antibody isolation for two sera. Patterns of virus-isolate neutralization can thus afford a detailed epitope-specific understanding of neutralizing-antibody responses to viral infection. PMID:23661761

  2. Cetuximab in combination with anti-human IgG antibodies efficiently down-regulates the EGF receptor by macropinocytosis

    SciTech Connect

    Berger, Christian [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway)] [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway); Madshus, Inger Helene [Institute of Pathology, University of Oslo, Rikshospitalet, 0027 Oslo (Norway) [Institute of Pathology, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway); Stang, Espen, E-mail: espsta@rr-research.no [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway)] [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway)

    2012-12-10

    The monoclonal antibody C225 (Cetuximab) blocks binding of ligand to the epidermal growth factor receptor (EGFR). In addition, it is known that incubation with C225 induces endocytosis of the EGFR. This endocytosis has previously been shown to be increased when C225 is combined with an additional monoclonal anti-EGFR antibody. However, the effects of antibody combinations on EGFR activation, endocytosis, trafficking and degradation have been unclear. By binding a secondary antibody to the C225-EGFR complex, we here demonstrate that a combination of antibodies can efficiently internalize and degrade the EGFR. Although the combination of antibodies activated the EGFR kinase and induced ubiquitination of the EGFR, the kinase activity was not required for internalization of the EGFR. In contrast to EGF-induced EGFR down-regulation, the antibody combination efficiently degraded the EGFR without initiating downstream proliferative signaling. The antibody-induced internalization of EGFR was found not to depend on clathrin and/or dynamin, but depended on actin polymerization, suggesting induction of macropinocytosis. Macropinocytosis may cause internalization of large membrane areas, and this could explain the highly efficient internalization of the EGFR induced by combination of antibodies. -- Highlight: Black-Right-Pointing-Pointer Cetuximab induced endocytosis of EGFR increases upon combination with anti-human IgG. Black-Right-Pointing-Pointer Antibody combination causes internalization of EGFR by macropinocytosis. Black-Right-Pointing-Pointer Antibody-induced internalization of EGFR is independent of EGFR kinase activity. Black-Right-Pointing-Pointer Antibody combination may have a zipper effect and cross-link EGFRs on neighboring cells.

  3. The pre-transmembrane region of the human immunodeficiency virus type-1 glycoprotein: a novel fusogenic sequence

    Microsoft Academic Search

    Tatiana Suárez; Shlomo Nir; Félix M. Goñi; Asier Saéz-Cirión; José L. Nieva

    2000-01-01

    We have investigated membrane interactions and perturbations induced by NH2-DKWASLWNWFNITNWLWYIK-COOH (HIVc), representing the membrane interface-partitioning region that precedes the transmembrane anchor of the human immunodeficiency virus type-1 gp41 fusion protein. The HIVc peptide bound with high affinity to electrically neutral vesicles composed of dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine and cholesterol (molar ratio, 1:1:1), and induced vesicle leakage and lipid mixing. Infrared spectra suggest

  4. Frequent Transmission of Immunodeficiency Viruses among Bobcats and Pumas

    Microsoft Academic Search

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

    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

  5. Gene therapy of primary T cell immunodeficiencies.

    PubMed

    Fischer, Alain; Hacein-Bey-Abina, Salima; Cavazzana-Calvo, Marina

    2013-08-10

    Gene therapy of severe combined immunodeficiencies has been proven to be effective to provide sustained correction of the T cell immunodeficiencies. This has been achieved for 2 forms of SCID, i.e SCID-X1 (?c deficiency) and adenosine deaminase deficiency. Occurrence of gene toxicity generated by integration of first generation retroviral vectors, as observed in the SCID-X1 trials has led to replace these vectors by self inactivated (SIN) retro(or lenti) viruses that may provide equivalent efficacy with a better safety profile. Results of ongoing clinical studies in SCID as well as in other primary immunodeficiencies, such as the Wiskott Aldrich syndrome, will be thus very informative. PMID:23583799

  6. [Adenosine deaminase in severe combined immunodeficiency syndrome].

    PubMed

    Pérez-Aguilar, Mary Carmen; Goncalves, Loredana; Bonfante-Cabarcas, Rafael

    2012-09-01

    Adenosine deaminase is an enzyme of the purine metabolism whose function is to convert adenosine to inosine and deoxyadenosine to deoxyinosine. The ecto-ADA1 binding to the cell surface through CD26 contributes to the regulation of cytokines and stimulates the proliferation of T cells by activating CD45. The deficiency of this enzyme generates the severe combined immunodeficiency syndrome, characterized by the accumulation of deoxyadenosine and adenine metabolites, which have toxic effects on lymphocytes, affecting DNA synthesis and consequently, clonal expansion. Early diagnosis of this immunodeficiency is essential, as it significantly reduces morbidity and mortality associated with recurrent infections. Recent advances in molecular biology and genetics have led to the identification of genetic defects of many primary immunodeficiencies and the development of promising diagnostic tools and treatment. PMID:23248974

  7. Adult-onset immunodeficiency in Thailand and Taiwan

    PubMed Central

    Browne, Sarah K.; Burbelo, Peter D.; Chetchotisakd, Ploenchan; Suputtamongkol, Yupin; Kiertiburanakul, Sasisopin; Shaw, Pamela A.; Kirk, Jennifer L.; Jutivorakool, Kamonwan; Zaman, Rifat; Ding, Li; Hsu, Amy P.; Patel, Smita Y.; Olivier, Kenneth N.; Lulitanond, Viraphong; Mootsikapun, Piroon; Anunnatsiri, Siriluck; Angkasekwinai, Nasikarn; Sathapatayavongs, Boonmee; Hsueh, Po-Ren; Shieh, Chi-Chang; Brown, Margaret R.; Thongnoppakhun, Wanna; Claypool, Reginald; Sampaio, Elizabeth P.; Thepthai, Charin; Waywa, Duangdao; Dacombe, Camilla; Reizes, Yona; Zelazny, Adrian M.; Saleeb, Paul; Rosen, Lindsey B.; Mo, Allen; Iadarola, Michael; Holland, Steven M.

    2014-01-01

    Background Autoantibodies against interferon-? are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown. Methods We enrolled 203 persons from sites in Thailand and Taiwan in five groups: 52 patients with disseminated, rapidly or slowly growing, nontuberculous mycobacterial infection (group 1); 45 patients with another opportunistic infection, with or without nontuberculous mycobacterial infection (group 2); 9 patients with disseminated tuberculosis (group 3); 49 patients with pulmonary tuberculosis (group 4); and 48 healthy controls (group 5). Clinical histories were recorded, and blood specimens were obtained. Results Patients in groups 1 and 2 had CD4+ T-lymphocyte counts that were similar to those in patients in groups 4 and 5, and they were not infected with the human immunodeficiency virus (HIV). Washed cells obtained from patients in groups 1 and 2 had intact cytokine production and a response to cytokine stimulation. In contrast, plasma obtained from these patients inhibited the activity of interferon-? in normal cells. High-titer anti–interferon-? autoantibodies were detected in 81% of patients in group 1, 96% of patients in group 2, 11% of patients in group 3, 2% of patients in group 4, and 2% of controls (group 5). Forty other anti-cytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte–macrophage colony-stimulating factor. No other anti-cytokine autoantibodies or genetic defects correlated with infections. There was no familial clustering. Conclusions Neutralizing anti–interferon-? autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection. PMID:22913682

  8. Latin America and Neutralism

    Microsoft Academic Search

    Nelson De sousa sampaio

    1965-01-01

    Neutralism finds particularly fertile ground in the underdeveloped countries of Asia and Africa. In Latin America, neutralism is used by leftist-oriented groups as a ve hicle to alienate their countries from an alignment with the West. Sometimes, neutralism appears under the disguise of nationalism, such as the tactical nationalism of the Communists and the rightist nationalism of some dictatorial movements.

  9. Induction of anti-HIV neutralizing antibodies by synthetic peptides.

    PubMed Central

    Chanh, T C; Dreesman, G R; Kanda, P; Linette, G P; Sparrow, J T; Ho, D D; Kennedy, R C

    1986-01-01

    Two synthetic peptides containing amino acid sequences analogous to the envelope glycoprotein of human T-lymphotropic virus (HTLV) type III (HTLV-III) and lymphadenopathy associated virus (LAV) were produced and used to immunize rabbits. The subsequent rabbit antisera neutralized HTLV-III infectivity in vitro. The two synthetic peptides corresponded to regions associated with the gp120 or gp41 subunits respectively, of human immunodeficiency virus (HIV). This data indicates that at least two neutralizing epitopes are present on the envelope glycoprotein of HIV and these epitopes are associated with two distinct virus envelope glycoproteins. Antisera generated against these peptides neutralized infectivity of two different isolates of HTLV-III. The data is discussed in terms of possible strategy for developing an effective vaccine against the etiologic agents of acquired immune deficiency syndrome (AIDS). PMID:3466790

  10. Neutral beam monitoring

    DOEpatents

    Fink, Joel H. (Livermore, CA)

    1981-08-18

    Method and apparatus for monitoring characteristics of a high energy neutral beam. A neutral beam is generated by passing accelerated ions through a walled cell containing a low energy neutral gas, such that charge exchange neutralizes the high energy ion beam. The neutral beam is monitored by detecting the current flowing through the cell wall produced by low energy ions which drift to the wall after the charge exchange. By segmenting the wall into radial and longitudinal segments various beam conditions are further identified.

  11. Interferon ? treatment of molluscum contagiosum in immunodeficiency

    PubMed Central

    Hourihane, J.; Hodges, E.; Smith, J.; Keefe, M.; Jones, A.; Connett, G.

    1999-01-01

    A sister (aged 6 years) and brother (aged 8 years) presented four months apart with severe molluscum contagiosum. Both children demonstrated clinical and laboratory evidence of combined immunodeficiency. The extent of skin involvement by molluscum contagiosum precluded conventional treatment as well as intralesional interferon ? (IFN?). Both subjects responded well to subcutaneous IFN?.?? PMID:10325766

  12. Prevalence of Primary Immunodeficiency in Korea

    PubMed Central

    Rhim, Jung Woo; Kim, Kyung Hyo; Kim, Dong Soo; Kim, Bong Seong; Kim, Jung Soo; Kim, Chang Hwi; Kim, Hwang Min; Park, Hee Ju; Pai, Ki Soo; Son, Byong Kwan; Shin, Kyung Sue; Oh, Moo Young; Woo, Young Jong; Yoo, Young; Lee, Kun Soo; Lee, Kyung Yil; Lee, Chong Guk; Lee, Joon Sung; Chung, Eun Hee; Choi, Eun Hwa; Hahn, Youn Soo; Park, Hyun Young

    2012-01-01

    This study represents the first epidemiological study based on the national registry of primary immunodeficiencies (PID) in Korea. Patient data were collected from 23 major hospitals. A total of 152 patients with PID (under 19 yr of age), who were observed from 2001 to 2005, have been entered in this registry. The period prevalence of PID in Korea in 2005 is 11.25 per million children. The following frequencies were found: antibody deficiencies, 53.3% (n = 81), phagocytic disorders, 28.9% (n = 44); combined immunodeficiencies, 13.2% (n = 20); and T cell deficiencies, 4.6% (n = 7). Congenital agammaglobulinemia (n = 21) and selective IgA deficiency (n = 21) were the most frequently reported antibody deficiency. Other reported deficiencies were common variable immunodeficiencies (n = 16), X-linked agammaglobulinemia (n = 15), IgG subclass deficiency (n = 4). Phagocytic disorder was mostly chronic granulomatous disease. A small number of patients with Wiskott-Aldrich syndrome, hyper-IgE syndrome, and severe combined immunodeficiency were also registered. Overall, the most common first manifestation was pneumonia. This study provides data that permit a more accurate estimation PID patients in Korea. PMID:22787376

  13. 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…

  14. Musculoskeletal Manifestations of Human Immunodeficiency Virus Infection

    Microsoft Academic Search

    Luis H. Silveira; Luis J. Jara; Píndaro Martínez-Osuna; Luis R. Espinoza; Mitchel J. Seleznick

    1991-01-01

    Human immunodeficiency virus (HIV) causes an infection characterized by a wide spectrum of clinical manifestations, including musculoskeletal conditions that have been recognized with increasing frequency in recent years. Arthralgia, usually of moderate intensity, intermittent, and oligoarticular, is the most frequent rheumatic manifestation of HIV; it occurs in approximately 35% of the cases. Knees, shoulders, and elbows are the most frequently

  15. Vaccination preserves CD4 memory T cells during acute simian immunodeficiency virus challenge

    PubMed Central

    Mattapallil, Joseph J.; Douek, Daniel C.; Buckler-White, Alicia; Montefiori, David; Letvin, Norman L.; Nabel, Gary J.; Roederer, Mario

    2006-01-01

    Acute simian immunodeficiency virus (SIV)/human immunodeficiency virus infection is accompanied by a massive destruction of CD4 memory T cells across all the tissue compartments. These early events set the course toward disease progression and immunodeficiency. Here, we demonstrate that prior vaccination reduces this destruction during acute SIV Mac251 infection, leading to better survival and long-term outcome. Systemic vaccination with a DNA-prime recombinant adenovirus boost regimen preserved memory CD4 T cells throughout the body. The vaccine regimen induced broad CD4 and CD8 T cell responses in all tissues examined and, importantly, induced antibodies that neutralized the primary isolate of SIV used for challenge. Finally, we demonstrate that the extent of preservation of the CD4 memory compartment during the acute phase provides a strong predictor for subsequent progression to death. Our data provide a mechanism to explain clinical observations that acute-phase viral loads predict long-term disease progression and underscore the need for interventions that protect against early destruction of CD4 memory T cells during acute infection. PMID:16735692

  16. Neutralizing Activity Against Clostridium difficile Toxin in the Supernatants of Cultured Colostral Cells

    PubMed Central

    Wada, Naoki; Nishida, Naomi; Iwaki, Susumu; Ohi, Hitoshi; Miyawaki, Toshio; Taniguchi, Noboru; Migita, Shunsuke

    1980-01-01

    Human colostral specimens were obtained from 60 Japanese postpartum women within the first 3 days after delivery. Neutralizing activity against Clostridium difficile toxin was evaluated with Y1 adrenal cells in miniculture. When Y1 adrenal cells were exposed briefly to the toxin, they showed a rounding response in culture, resembling that effected by Escherichia coli enterotoxin; however, preincubation of the toxin with aqueous phase of colostrum significantly reduced its cytopathic effect on Y1 adrenal cells. Of 60 colostral specimens, 17 samples had neutralizing activity against the toxin. Cell-free supernatants of colostral cells cultured for 7 days without mitogens contained significant amounts of both immunoglobulin A (IgA) and IgM, but very small amounts of IgG. Neutralizing activity of cell-free supernatants of cultured colostral cells was evaluated as described above. Neutralizing activity against the toxin was identified in five samples of culture supernatants out of 60 colostral cell specimens. In all five cases, the aqueous phase of colostrum also had a neutralizing effect against C. difficile toxin. Neutralizing activity against the toxin found in five supernatants of cultured colostral cells was completely abolished only by anti-human IgA antibody as assessed by immune precipitation. PMID:7216424

  17. Human Immunodeficiency Virus Env-Independent Infection of Human CD4? Cells

    PubMed Central

    Pang, Shen; Yu, Duan; An, Dong Sung; Baldwin, Gayle C.; Xie, Yiming; Poon, Betty; Chow, Yen-Hung; Park, No-Hee; Chen, Irvin S. Y.

    2000-01-01

    CD4? epithelial cells covering mucosal surfaces serve as the primary barrier to prevent human immunodeficiency virus type 1 (HIV-1) infection. We used HIV-1 vectors carrying the enhanced green fluorescent protein gene as a reporter gene to demonstrate that HIV-1 can infect some CD4? human epithelial cell lines with low but significant efficiencies. Importantly, HIV-1 infection of these cell lines is independent of HIV-1 envelope proteins. The Env-independent infection of CD4? cells by HIV-1 suggests an alternative pathway for HIV-1 transmission. Even on virions bearing Env, a neutralizing antibody directed against gp120 is incapable of neutralizing the infection of these cells, thus raising potential implications for HIV-1 vaccine development. PMID:11069994

  18. Effects of Early IL17A Neutralization on Disease Induction in a Primate Model of Experimental Autoimmune Encephalomyelitis

    Microsoft Academic Search

    Yolanda S. Kap; S. Anwar Jagessar; Nikki van Driel; Erwin Blezer; Jan Bauer; Marjan van Meurs; Paul Smith; Jon D. Laman; Bert A. ‘t Hart

    We report on the effect of antibody-mediated neutralization of interleukin (IL)-17A in a non-human primate experimental autoimmune\\u000a encephalomyelitis (EAE) model induced with recombinant human myelin oligodendrocyte glycoprotein (rhMOG). We tested a human-anti-human\\u000a IL-17A-antibody in two doses (3 and 30 mg\\/kg) against placebo (PBS). The treatment was started 1 day before EAE induction\\u000a and continued throughout the experiment. Although all monkeys developed clinically

  19. ALEX neutral beam probe

    SciTech Connect

    Pourrezaei, K.

    1982-01-01

    A neutral beam probe capable of measuring plasma space potential in a fully 3-dimensional magnetic field geometry has been developed. This neutral beam was successfully used to measure an arc target plasma contained within the ALEX baseball magnetic coil. A computer simulation of the experiment was performed to refine the experimental design and to develop a numerical model for scaling the ALEX neutral beam probe to other cases of fully 3-dimensional magnetic field. Based on this scaling a 30 to 50 keV neutral cesium beam probe capable of measuring space potential in the thermal barrier region of TMX Upgrade was designed.

  20. Malignant syphilis with human immunodeficiency virus infection

    PubMed Central

    Rajan, Jiby; Prasad, P. V. S.; Chockalingam, K.; Kaviarasan, P. K.

    2011-01-01

    Malignant syphilis or Lues maligna, commonly reported in the pre-antibiotic era, has now seen a resurgence with the advent of human immunodeficiency virus (HIV). Immunosuppression and sexual promiscuity set the stage for this deadly association of HIV and Treponema pallidum that can manifest atypically and can prove to cause diagnostic problems. We report one such case in a 30-year-old female who responded favorably to treatment with penicillin. PMID:23130209

  1. Familial hepatopulmonary syndrome in common variable immunodeficiency.

    PubMed

    Holmes, S N; Condliffe, A; Griffiths, W; Baxendale, H; Kumararatne, D S

    2015-04-01

    Common Variable Immunodeficiency (CVID) comprises a heterogeneous group of primary antibody deficiencies which lead to a range of complications, including infectious, neoplastic and inflammatory disorders. This report describes monozygotic twin brothers with CVID who developed cryptogenic liver disease and subsequently hepatopulmonary syndrome (HPS). This is the second report of the association of HPS and CVID. Its occurrence in two identical twins implicates a genetic basis. PMID:25708586

  2. 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

  3. Neutral hydrogen in galaxies

    Microsoft Academic Search

    R. Sancisi

    1981-01-01

    Recent studies of the distribution and dynamics of neutral hydrogen gas in galaxies and galactic neighborhoods are discussed. Observations of elliptical galaxies have shown them to contain little neutral hydrogen, with upper limits corresponding to less than 0.1% of the total mass. In the two ellipticals studied in detail by the Westerbork Synthesis Radio Telescope, the H I appears to

  4. Neutralizing Acids and Bases

    NSDL National Science Digital Library

    2012-04-08

    Learners use their knowledge of color changes with red cabbage indicator to neutralize an acidic solution with a base and then neutralize a basic solution with an acid. Use this as a follow-up activity to the related activity, "Color Changes with Acids and Bases."

  5. Decelerating Neutral Dipolar Molecules

    Microsoft Academic Search

    Hendrick L. Bethlem; Giel Berden; Gerard Meijer

    1999-01-01

    It is experimentally demonstrated that a beam of neutral dipolar molecules can be efficiently decelerated with a time-varying electric field. A pulsed beam of neutral metastable CO molecules is slowed down from 225 m\\/s ( Ekin = 59 cm-1) to 98 m\\/s ( Ekin = 11 cm-1) upon passage through an array of 63 synchronously pulsed electric field stages.

  6. Neutralizing the HIV reservoir.

    PubMed

    Marsden, Matthew D; Zack, Jerome A

    2014-08-28

    Halper-Stromberg et al. use a humanized mouse model to demonstrate that broadly neutralizing antibodies, when administered with a combination of HIV latency activators, can reduce persistent HIV reservoirs, as measured by plasma virus rebound. Their results support the use of broadly neutralizing antibodies in HIV-reservoir-purging strategies. PMID:25171398

  7. Severe combined immunodeficiency due to adenosine deaminase deficiency.

    PubMed

    Hussain, Waqar; Batool, Asma; Ahmed, Tahir Aziz; Bashir, Muhammad Mukarram

    2012-03-01

    Severe Combined Immunodeficiency is the term applied to a group of rare genetic disorders characterised by defective or absent T and B cell functions. Patients usually present in first 6 months of life with respiratory/gastrointestinal tract infections and failure to thrive. Among the various types of severe combined immunodeficiency, enzyme deficiencies are relatively less common. We report the case of a 6 years old girl having severe combined immunodeficiency due to adenosine deaminase deficiency. PMID:22764473

  8. 78 FR 33848 - Draft Guidance for Industry on Human Immunodeficiency Virus-1 Infection: Developing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-05

    ...for Industry on Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral...industry entitled ``Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral...industry entitled ``Human Immunodeficiency Virus-1 Infection: Developing...

  9. Exploring the energy profile of human IgG/rat anti-human IgG interactions by dynamic force spectroscopy.

    PubMed

    Lv, Zhengjian; Wang, Jianhua; Chen, Guoping

    2012-06-01

    Interactions between antibody and antigen molecules play essential roles in biological recognition processes as well as medical diagnosis. Therefore, an understanding of the underlying mechanism of antibody-antigen interactions at the single molecular level would be beneficial. In the present study, human immunoglobulin (IgG) tethered cantilevers and rat anti-human IgG functionalized gold surfaces were fabricated by using self-assembled monolayers method. Dynamic force spectroscopy was employed to characterize the interactions between human (IgG) and rat anti-human IgG at the single-molecule level. The unbinding forces were determined to be 44.6 ± 0.8, 65.8 ± 3.0, 108.1 ± 4.1, 131.1 ± 11.2, 149.5 ± 4.7, 239.5 ± 3.1 and 294.7 ± 7.7 pN with ramping loading rates of 514, 1,127, 3,058, 7,215, 15,286, 31,974 and 50,468 pN s(-1), respectively. In addition, the unbinding forces were found to be increasing with the logarithm of apparent loading rates in a linear way. Fitting data group resulted in two distinct linear parts, suggesting there are two energy barriers. The corresponding distances in the bound and transition states (x ( ? )) and the dissociation rates (K ( off )) were calculated to be 0.129 ± 0.006 nm, 3.986 ± 0.162 s(-1) for the outer barrier and 0.034 ± 0.001 nm, 36.754 ± 0.084 s(-1) for the inner barrier. Such findings hold promise of screening novel drugs and discerning different unbinding modes of biological molecules. PMID:22588725

  10. Investigating antibody neutralization of lyssaviruses using lentiviral pseudotypes: a cross-species comparison

    Microsoft Academic Search

    Edward Wright; Nigel J. Temperton; Denise A. Marston; Lorraine M. McElhinney; Anthony R. Fooks; Robin A. Weiss

    2008-01-01

    Cross-neutralization between rabies virus (RABV) and two European bat lyssaviruses (EBLV-1 and -2) was analysed using lentiviral pseudotypes as antigen vectors. Glycoprotein (G-protein) cDNA from RABV challenge virus standard-11 (CVS-11) and EBLV-1 and -2 were cloned and co-expressed with human immunodeficiency virus (HIV) or murine leukemia virus (MLV) gag- pol and packageable green fluorescent protein (GFP) or luciferase reporter genes

  11. Equivalent Neutral Wind

    NASA Technical Reports Server (NTRS)

    Liu, W. Timothy; Tang, Wenqing

    1996-01-01

    The definition of equivalent neutral wind and the rationale for using it as the geophysical product of a spaceborne scatterometer are reviewed. The differences between equivalent neutral wind and actual wind, which are caused by atmospheric density stratification, are demonstrated with measurements at selected locations. A method of computing this parameter from ship and buoy measurements is described and some common fallacies in accounting for the effects of atmospheric stratification on wind shear are discussed. The computer code for the model to derive equivalent neutral wind is provided.

  12. Multispecific Vaccine-Induced Mucosal Cytotoxic T Lymphocytes Reduce Acute-Phase Viral Replication but Fail in Long-Term Control of Simian Immunodeficiency Virus SIVmac239

    Microsoft Academic Search

    Thorsten U. Vogel; Matthew R. Reynolds; Deborah H. Fuller; Kathy Vielhuber; Tim Shipley; James T. Fuller; Kevin J. Kunstman; Gerd Sutter; Marta L. Marthas; Volker Erfle; Steven M. Wolinsky; Chenxi Wang; David B. Allison; Erling W. Rud; Nancy Wilson; David Montefiori; John D. Altman; David I. Watkins

    2003-01-01

    Given the current difficulties generating vaccine-induced neutralizing antibodies to human immunodefi- ciency virus (HIV), the focus of the vaccine community has shifted toward creating cytotoxic-T-lymphocyte (CTL)-based vaccines. Recent reports of CTL-based vaccine trials in macaques challenged with simian\\/human immunodeficiency virus SHIV-89.6P have supported the notion that such vaccines can ameliorate the course of disease. However, almost all of these studies

  13. Protection in Macaques Immunized with HIV-1 Candidate Vaccines Can Be Predicted Using the Kinetics of Their Neutralizing Antibodies

    PubMed Central

    Davis, David; Koornstra, Wim; Mortier, Daniella; Fagrouch, Zahra; Verschoor, Ernst J.; Heeney, Jonathan L.; Bogers, Willy M. J. M.

    2011-01-01

    Background A vaccine is needed to control the spread of human immunodeficiency virus type 1 (HIV-1). An in vitro assay that can predict the protection induced by a vaccine would facilitate the development of such a vaccine. A potential candidate would be an assay to quantify neutralization of HIV-1. Methods and Findings We have used sera from rhesus macaques that have been immunized with HIV candidate vaccines and subsequently challenged with simian human immunodeficiency virus (SHIV). We compared neutralization assays with different formats. In experiments with the standardized and validated TZMbl assay, neutralizing antibody titers against homologous SHIVSF162P4 pseudovirus gave a variable correlation with reductions in plasma viremia levels. The target cells used in the assays are not just passive indicators of virus infection but are actively involved in the neutralization process. When replicating virus was used with GHOST cell assays, events during the absorption phase, as well as the incubation phase, determine the level of neutralization. Sera that are associated with protection have properties that are closest to the traditional concept of neutralization: the concentration of antibody present during the absorption phase has no effect on the inactivation rate. In GHOST assays, events during the absorption phase may inactivate a fixed number, rather than a proportion, of virus so that while complete neutralization can be obtained, it can only be found at low doses particularly with isolates that are relatively resistant to neutralization. Conclusions Two scenarios have the potential to predict protection by neutralizing antibodies at concentrations that can be induced by vaccination: antibodies that have properties close to the traditional concept of neutralization may protect against a range of challenge doses of neutralization sensitive HIV isolates; a window of opportunity also exists for protection against isolates that are more resistant to neutralization but only at low challenge doses. PMID:22216149

  14. Is dispersal neutral?

    PubMed

    Lowe, Winsor H; McPeek, Mark A

    2014-08-01

    Dispersal is difficult to quantify and often treated as purely stochastic and extrinsically controlled. Consequently, there remains uncertainty about how individual traits mediate dispersal and its ecological effects. Addressing this uncertainty is crucial for distinguishing neutral versus non-neutral drivers of community assembly. Neutral theory assumes that dispersal is stochastic and equivalent among species. This assumption can be rejected on principle, but common research approaches tacitly support the 'neutral dispersal' assumption. Theory and empirical evidence that dispersal traits are under selection should be broadly integrated in community-level research, stimulating greater scrutiny of this assumption. A tighter empirical connection between the ecological and evolutionary forces that shape dispersal will enable richer understanding of this fundamental process and its role in community assembly. PMID:24962790

  15. In vitro antigen challenge of human antibody libraries for vaccine evaluation: the human immunodeficiency virus type 1 envelope.

    PubMed Central

    Parren, P W; Fisicaro, P; Labrijn, A F; Binley, J M; Yang, W P; Ditzel, H J; Barbas, C F; Burton, D R

    1996-01-01

    Human antibody responses, or versions thereof, can be cloned as phage display libraries. In vaccine evaluation, the possibility therefore exists of challenging the human response in vitro, rather than in vivo, in order to assist in establishing the most promising vaccine leads. The characteristics of the antibodies retrieved directly indicate the strengths and weaknesses of the vaccine at the molecular level. We applied this approach to compare recombinant and native human immunodeficiency virus type 1 envelope preparations. We conclude that recombinant gp160, gp140, and, to a lesser extent, gp120 present epitopes around the CD4 binding site in a conformation different from that of the native multimer and contrary to expected vaccine requirements. Antibodies to the potently neutralizing b12 epitope were selected preferentially from an immune library by purified human immunodeficiency virus type 1 virions. This suggests that b12 is a major epitope on the virions, in contrast to recombinant envelope preparations, in which related, weakly neutralizing epitopes predominate. Although the majority of virions in the preparation used are expected to be noninfective, it appears that they predominantly express a native envelope configuration and would be able to elicit potent neutralizing antibodies. PMID:8971041

  16. Impact of Simian Immunodeficiency Virus Infection on Chimpanzee Population Dynamics

    Microsoft Academic Search

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

    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

  17. Modulation of simian immunodeficiency virus neuropathology by dopaminergic drugs

    Microsoft Academic Search

    S. Czub; M. Czub; E. Koutsilieri; S. Sopper; F. Villinger; J. G. Müller; C. Stahl-Hennig; P. Riederer; V. ter Meulen; G. Gosztonyi

    2004-01-01

    Drug abuse and human immunodeficiency virus (HIV) infection seem to cause cumulative damage in the central nervous system (CNS). Elevated extracellular dopamine is thought to be a prime mediator of the reinforcing effects of addictive substances. To investigate the possible role of increased dopamine availability in the pathogenesis of HIV dementia, simian immunodeficiency virus (SIV)-infected monkeys were treated with dopaminergic

  18. Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies

    ClinicalTrials.gov

    2009-10-14

    Immunologic Deficiency Syndromes; Chediak-Higashi Syndrome; Common Variable Immunodeficiency; Graft Versus Host Disease; X-Linked Lymphoproliferative Syndrome; Familial Erythrophagocytic Lymphohistiocytosis; Hemophagocytic Lymphohistiocytosis; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; X-linked Hyper IgM Syndrome; Severe Combined Immunodeficiency; Leukocyte Adhesion Deficiency Syndrome; Virus-Associated Hemophagocytic Syndrome

  19. [Gene therapy for severe combined immunodeficiency].

    PubMed

    Petersen, Line Barrett; Jensen, Thomas G

    2010-06-01

    New results with gene therapy for severe combined immunodeficiency due to adenosine deaminase deficiency are promising. We review a clinical project in which ten children were treated with gene modified autologous haematopoietic stem cells. After treatment, eight patients were able to do without enzyme-replacement therapy, and nine patients showed improved immune function and sustained low concentration of toxic metabolites. No clonal outgrow was observed indicating a limited risk for future malignant development. Despite these promising results, the safety of gene therapy can still be improved. PMID:20534204

  20. Screening for severe combined immunodeficiency in neonates

    PubMed Central

    Kelly, Brian T; Tam, Jonathan S; Verbsky, James W; Routes, John M

    2013-01-01

    Severe combined immunodeficiency (SCID) is a rare disease that severely affects the cellular and humoral immune systems. Patients with SCID present with recurrent or severe infections and often with chronic diarrhea and failure to thrive. The disease is uniformly fatal, making early diagnosis essential. Definitive treatment is hematopoietic stem cell transplantation, with best outcomes prior to 3.5 months of age. Newborn screening for SCID using the T-cell receptor excision circle assay has revolutionized early identification of infants with SCID or severe T-cell lymphopenia. PMID:24068875

  1. Barrier methods for human immunodeficiency virus prevention.

    PubMed

    Eaton, Ellen F; Hoesley, Craig J

    2014-12-01

    Condoms remain the most effective barrier against the sexual transmission of the human immunodeficiency virus (HIV). Male condoms have proven to be 80% to 90% effective, and female condoms have similar results. Poor adherence and improper use limit their effectiveness. In addition to condoms, microbicides are a promising barrier against HIV transmission. More than 50 candidate topical microbicide compounds have undergone preclinical or clinical testing in the last 10 years, but there are currently no US Food and Drug Administration (FDA)-approved compounds. Rectal microbicides are also being developed, as anal receptive sex is an effective mode of HIV transmission. PMID:25455315

  2. Policy on Gender Neutral Housing Policy on Gender-Neutral

    E-print Network

    Sridhar, Srinivas

    Policy on Gender Neutral Housing 10/01/2013 Policy on Gender-Neutral Housing I. Purpose and Scope Gender-neutral housing gives students the option to reside with another student, regardless of sex, gender, gender identity or gender expression. II. Definitions Gender-neutral housing is defined

  3. Inhibition of human immunodeficiency virus type 1 replication by a Tat-activated, transduced interferon gene: targeted expression to human immunodeficiency virus type 1-infected cells.

    PubMed Central

    Su, Y; Popik, W; Pitha, P M

    1995-01-01

    We have examined the feasibility of using interferon (IFN) gene transfer as a novel approach to anti-human immunodeficiency virus type 1 (HIV-1) therapy in this study. To limit expression of a transduced HIV-1 long terminal repeat (LTR)-IFNA2 (the new approved nomenclature for IFN genes is used throughout this article) hybrid gene to the HIV-1-infected cells, HIV-1 LTR was modified. Deletion of the NF-kappa B elements of the HIV-1 LTR significantly inhibited Tat-mediated transactivation in T-cell lines, as well as in a monocyte line, U937. Replacement of the NF-kappa B elements in the HIV-1 LTR by a DNA fragment derived from the 5'-flanking region of IFN-stimulated gene 15 (ISG15), containing the IFN-stimulated response element, partially restored Tat-mediated activation of LTR in T cells as well as in monocytes. Insertion of this chimeric promoter (ISG15 LTR) upstream of the human IFNA2 gene directed high levels of IFN synthesis in Tat-expressing cells, while this promoter was not responsive to tumor necrosis factor alpha-mediated activation. ISG15-LTR-IFN hybrid gene inserted into the retrovirus vector was transduced into Jurkat and U937 cells. Selected transfected clones produced low levels of IFN A (IFNA) constitutively, and their abilities to express interleukin-2 and interleukin-2 receptor upon stimulation with phytohemagglutinin and phorbol myristate acetate were retained. Enhancement of IFNA synthesis observed upon HIV-1 infection resulted in significant inhibition of HIV-1 replication for a period of at least 30 days. Virus isolated from IFNA-producing cells was able to replicate in the U937 cells but did not replicate efficiently in U937 cells transduced with the IFNA gene. These results suggest that targeting IFN synthesis to HIV-1-infected cells is an attainable goal and that autocrine IFN synthesis results in a long-lasting and permanent suppression of HIV-1 replication. PMID:7983701

  4. 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…

  5. Testicular tumor and the acquired immunodeficiency syndrome.

    PubMed

    Buzelin, F; Karam, G; Moreau, A; Wetzel, O; Gaillard, F

    1994-01-01

    Immunocompromised patients, particularly those suffering from the acquired immunodeficiency syndrome (AIDS), present an increased risk of tumoral pathology. From the observation of a testicular lymphoma associated with Epstein-Barr virus in a HIV + patient, we review 19 cases of testicular tumor in HIV + patients previously published in the literature. These tumors are either lymphomas (4 cases) or germ cell tumors (15 cases). Their diagnosis was not difficult, although in the first stages enlarged and painful testicles are often wrongly identified as orchiepididymitis and treated as such. Therapy management proves to be delicate as a result of the significant tumor spread seen in these patients with dysfunctional immune systems. Regarding lymphomas, a low-dose multiagent chemotherapy with intrathecal chemotherapy was recommended by Levine. Concerning germ cell tumors, Wilson prefers an instant aggressive treatment with retroperitoneal lymphadenectomy (whether or not combined with chemotherapy) to avoid the risk of recurrence. In fact, tumor relapses will be difficult to control in the progressive stages of immunodeficiency syndrome. PMID:7925534

  6. Vaccine use in primary immunodeficiency disorders.

    PubMed

    Principi, Nicola; Esposito, Susanna

    2014-06-24

    Primary immunodeficiency disorders (PIDs) are a heterogeneous group of rare, congenital and genetically determined conditions caused by one or more defects of innate and/or adaptive immunity. In subjects suffering from PIDs, an unusually increased susceptibility to infections is demonstrated. As infections condition the final prognosis of most PIDs, clearly defined prophylactic practices are essential. In most cases, intravenously or subcutaneously administered immunoglobulin remains the mainstay of treatment, although antibiotics and antifungals can be added under some conditions, particularly when the infections are highly recurrent despite immunoglobulin replacement. Vaccines could also play a role, but their administration leads to different results depending on the type of PID: in some cases, immune response is not impaired, and vaccines can evoke the same protection as that usually induced in healthy subjects; in others, the immunodeficiency significantly interferes with antigen stimulation of the immune system and, depending on the type and degree of impairment, little or no protection is evoked. Moreover, particularly when live vaccines are given, significant vaccine-related adverse events can occur, including the emergence of disease from vaccine strains. The main aim of this paper is to discuss what is currently known about how and when vaccines can be used in patients with PIDs in order to facilitate physician choices and assure the best possible patient protection. PMID:24837766

  7. Covert vertical transmission of feline immunodeficiency virus.

    PubMed

    Allison, Robin W; Hoover, Edward A

    2003-05-01

    Covert vertical transmission of feline immunodeficiency virus (FIV), the feline counterpart of human immunodeficiency virus type 1 (HIV-1), was identified in kittens born to FIV-infected cats. DNA PCR detected FIV gag and env sequences in tissues from kittens nonviable at birth, and in viable kittens monitored postnatally and necropsied at either 11 weeks or 1 year of age. Although FIV DNA was detected in initial blood samples from all 16 viable kittens, viral DNA became increasingly difficult to detect over time and infectious virus could rarely be demonstrated. Only maternal FIV antibody was detected in kitten plasma during the entire postnatal observation period, and kittens remained healthy, with normal CD4:CD8 T cell ratios at >14 months of age. Thus, mother-to-offspring FIV exposure, occurring in utero and postnatally, can result in covert infection in kittens with virus sequestered and contained in tissue sites. These findings appear directly relevant to suspected transient HIV infections and reports of HIV-specific cellular immune responses in highly exposed seronegative adults and uninfected infants born to HIV-positive women. PMID:12804000

  8. 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

  9. Simian immunodeficiency virus DNA vaccine trial in macaques.

    PubMed Central

    Lu, S; Arthos, J; Montefiori, D C; Yasutomi, Y; Manson, K; Mustafa, F; Johnson, E; Santoro, J C; Wissink, J; Mullins, J I; Haynes, J R; Letvin, N L; Wyand, M; Robinson, H L

    1996-01-01

    An experimental vaccine consisting of five DNA plasmids expressing different combinations and forms of simian immunodeficiency virus-macaque (SIVmac) proteins has been evaluated for the ability to protect against a highly pathogenic uncloned SIVmac251 challenge. One vaccine plasmid encoded nonreplicating SIVmac239 virus particles. The other four plasmids encoded secreted forms of the envelope glycoproteins of two T-cell-tropic relatives (SIVmac239 and SIVmac251) and one monocyte/macrophage-tropic relative (SIVmac316) of the uncloned challenge virus. Rhesus macaques were inoculated with DNA at 1 and 3, 11 and 13, and 21 and 23 weeks. Four macaques were inoculated intravenously, intramuscularly, and by gene gun inoculations. Three received only gene gun inoculations. Two control monkeys were inoculated with control plasmids by all three routes of inoculation. Neutralizing antibody titers of 1:216 to 1:768 were present in all of the vaccinated monkeys after the second cluster of inoculations. These titers were transient, were not boosted by the third cluster of inoculations, and had fallen to 1:24 to 1:72 by the time of challenge. Cytotoxic T-cell activity for Env was also raised in all of the vaccinated animals. The temporal appearance of cytotoxic T cells was similar to that of antibody. However, while antibody responses fell with time, cytotoxic T-cell responses persisted. The SIVmac251 challenge was administered intravenously at 2 weeks following the last immunization. The DNA immunizations did not prevent infection or protect against CD4+ cell loss. Long-term chronic levels of infection were similar in the vaccinated and control animals, with 1 in 10,000 to 1 in 100,000 peripheral blood cells carrying infectious virus. However, viral loads were reduced to the chronic level over a shorter period of time in the vaccinated groups (6 weeks) than in the control group (12 weeks). Thus, the DNA vaccine raised both neutralizing antibody and cytotoxic T-lymphocyte responses and provided some attenuation of the acute phase of infection, but it did not prevent the loss of CD4+ cells. PMID:8648735

  10. The Neutral Medium

    E-print Network

    Robert Braun

    2005-01-17

    We consider the physical conditions of the neutral medium within, and in the environments of, galaxies. The basic physical and morphological properties of the neutral medium within galaxy disks are now quite well-constrained. Systematic variations in temperature and phase-balance (of cool versus warm neutral gas) are indicated as a function of both radius and z-height. Interestingly, the cool medium line-widths are observed to be dominated by turbulent energy injection within cells of 10 pc to 1 kpc size. Deep new observations reveal that 5-10% of the neutral medium is associated within an extended halo which rotates more slowly and experiences radial inflow. Much of this component is likely to be associated with a ``galactic fountain'' type of phenomenon. However, compelling evidence is also accumulating for the importance of tidal disruption of satellites as well as continuous accretion (of both diffuse and discrete components) in fueling galaxy halos and disks. Continued fueling is even observed on scales of 100's of kpc in galaxy environments, where the neutral component is likely to be merely a trace constituent of a highly ionized plasma.

  11. The effectiveness of an anti-human IL-6 receptor monoclonal antibody combined with chemotherapy to target colon cancer stem-like cells.

    PubMed

    Ying, Jin; Tsujii, Masahiko; Kondo, Jumpei; Hayashi, Yoshito; Kato, Motohiko; Akasaka, Tomofumi; Inoue, Takuta; Shiraishi, Eri; Inoue, Tahahiro; Hiyama, Satoshi; Tsujii, Yoshiki; Maekawa, Akira; Kawai, Shoichiro; Fujinaga, Tetsuji; Araki, Maekawa; Shinzaki, Shinichiro; Watabe, Kenji; Nishida, Tsutomu; Iijima, Hideki; Takehara, Tetsuo

    2015-04-01

    Recent studies have demonstrated that cancer stem cells (CSCs) can initiate and sustain tumor growth and exhibit resistance to clinical cytotoxic therapies. Therefore, CSCs represent the main target of anticancer therapy. Interleukin-6 (IL-6) promotes cellular proliferation and drug resistance in colorectal cancer, and its serum levels correlate with patient survival. Therefore, IL-6 and its downstream signaling molecule the signal transducer and activator of transcription-3 (STAT3) represent potential molecular targets. In the present study, we investigated the effects of IL-6 and its downstream signaling components on stem cell biology, particularly the chemoresistance of CSCs, to explore potential molecular targets for cancer therapy. The colon cancer cell line WiDr was cultured in serum-free, non-adherent, and three-dimensional spheroid-forming conditions to enrich the stem cell-like population. Spheroid-forming cells slowly proliferated and expressed high levels of Oct-4, Klf4, Bmi-1, Lgr5, IL-6, and Notch 3 compared with adherent cells. Treatment with an anti-human IL-6 receptor monoclonal antibody reduced spheroid formation, stem cell-related gene expression, and 5-fluorouracil (5-FU) resistance. In addition, IL-6 treatment enhanced the levels of p-STAT3 (Tyr705), the expression of Oct-4, Klf4, Lgr5, and Notch 3, and chemoresistance to 5-FU. siRNA targeting Notch 3 suppressed spheroid formation, Oct-4 and Lgr5 expression, and 5-FU chemoresistance, whereas STAT3 inhibition enhanced Oct-4, Klf4, Lgr5, and Notch 3 expression and 5-FU chemoresistance along with reduced spheroid growth. Taken together, these results indicate that IL-6 functions in dichotomous pathways involving Notch 3 induction and STAT3 activation. The former pathway is involved in cancer stem-like cell biology and enhanced chemoresistance, and the latter pathway leads to accelerated proliferation and reduced chemoresistance. Thus, an anti-human IL-6 receptor monoclonal antibody or Notch 3 inhibition may be superior to STAT3 inhibition for CSC-targeting therapies concomitant with anticancer drugs. PMID:25625841

  12. Lithium jet neutralizer to improve negative hydrogen neutral beam systems

    NASA Astrophysics Data System (ADS)

    Grisham, L. R.

    2007-10-01

    Hydrogen isotope neutral beam systems for heating and current drive in magnetic fusion energy devices have always used gas cells of the beam isotope to convert a portion of the energetic ions into neutral atoms. In the design of negative-ion based neutral beams for the ITER tokamak [R. Aymar V. A. Chuyanov, M. Huguet et al., Nuclear Fusion 41, 1301 (2001)], or for future fusion reactors, the large gas load from a traditional neutralizer cell causes many problems, including increased heat loads on the accelerator and ion source, reduced beam efficiency due to premature neutralization in the accelerator and reionization after the neutralizer, and the need to stop the beam for regeneration of the cryopanels, reducing the attractiveness of beams for reactors. We explore several approaches to decrease the neutralizer gas throughput, and conclude that a supersonic lithium vapor jet neutralizer is the most appropriate, and also affords a higher neutralization efficiency than does a hydrogen isotope gas cell.

  13. Lithium jet neutralizer to improve negative hydrogen neutral beam systems

    SciTech Connect

    Grisham, L. R. [Princeton University, Plasma Physics Laboratory, P.O. Box 451, Princeton, New Jersey 08543 (United States)

    2007-10-15

    Hydrogen isotope neutral beam systems for heating and current drive in magnetic fusion energy devices have always used gas cells of the beam isotope to convert a portion of the energetic ions into neutral atoms. In the design of negative-ion based neutral beams for the ITER tokamak [R. Aymar V. A. Chuyanov, M. Huguet et al., Nuclear Fusion 41, 1301 (2001)], or for future fusion reactors, the large gas load from a traditional neutralizer cell causes many problems, including increased heat loads on the accelerator and ion source, reduced beam efficiency due to premature neutralization in the accelerator and reionization after the neutralizer, and the need to stop the beam for regeneration of the cryopanels, reducing the attractiveness of beams for reactors. We explore several approaches to decrease the neutralizer gas throughput, and conclude that a supersonic lithium vapor jet neutralizer is the most appropriate, and also affords a higher neutralization efficiency than does a hydrogen isotope gas cell.

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

    PubMed

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

    2015-05-01

    Neurological complications in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) are still common, even in the era of highly active antiretroviral therapy. Opportunistic infections, immune reconstitution, the virus itself, antiretroviral drugs and neurocognitive disorders have to be considered when establishing the differential diagnosis. Toxoplasmic encephalitis remains the major cause of space-occupying lesions in the brain of patients with HIV/AIDS; however, spinal cord involvement has been reported infrequently. Here, we review spinal cord toxoplasmosis in HIV infection and illustrate the condition with a recent case from our hospital. We suggest that most patients with HIV/AIDS and myelitis with enhanced spine lesions, multiple brain lesions and positive serology for Toxoplasma gondii should receive immediate empirical treatment for toxoplasmosis, and a biopsy should be performed in those cases without clinical improvement or with deterioration. PMID:25835092

  15. A comparison of in vitro, immuno-suppressive and clinical effects of goat and horse anti-human thymocyte globulin in macaca monkeys

    PubMed Central

    Kelly, G. E.; Sheil, A. G. R.; Mears, D. C.

    1973-01-01

    Anti-human thymocyte globulin was raised in four goats and two horses. The in vitro properties were defined, and clinical effects and immunosuppressive efficacy were tested in Macaca monkeys bearing skin xenografts or allografts. All goat and one horse ALG preparation produced significant graft prolongation; one horse ALG showed no in vivo immune suppression. Graft survival correlated well with the rosette-inhibiting activities of the various ALG batches. Goat ALG was well tolerated and produced no local, systemic or anaphylactic reactions; both horse ALG preparations consistently produced local reactions, serum sickness, and, occasionally severe anaphylactic reactions in sensitized and non-sensitized monkeys. Prolonged treatment with goat or horse ALG for up to 10 months caused lymphocyte depletion and plasmacytosis in lymph nodes and spleen but no other apparent pathological changes in a wide variety of tissues studied; infective complications did not occur. Goat IgG was more immunogenic than horse but circulating antibody titres to xenogenic IgG could not be related to clinical responses to ALG, to deposition of xenogenic IgG in kidneys, or to immunosuppressive potency of ALG batches. It was concluded that goat ALG was consistently more potent and less toxic than horse ALG. PMID:4197827

  16. Protective effects of HFE7A, mouse anti-human/mouse Fas monoclonal antibody against acute and lethal hepatic injury induced by Jo2

    PubMed Central

    Watanabe, Kenji; Takahashi, Shu; Ichikawa, Kimihisa

    2009-01-01

    HFE7A is a mouse anti-human/mouse Fas monoclonal antibody which, protects mice from fulminant hepatitis induced by Jo2. Herein, we report on the mechanism of the protective effect of HFE7A against Jo2-induced acute and lethal hepatic injury. HFE7A reduced the serum aminotransferase level which was elevated after Jo2 injection. HFE7A also inhibited caspase activation and mitochondrial depolarization in hepatocytes derived from apoptosis induced by Jo2 injection. The protective effect of HFE7A against Jo2-induced apoptosis in mouse hepatocytes was reproducible in vitro. The cell death and caspase activation in isolated mouse hepatocytes were induced by incubating these cells with Jo2 in vitro, and HFE7A inhibited the cell death and caspase activation in mouse hepatocytes in a dose-dependent manner. The affinity of HFE7A to mouse Fas was lower than that of Jo2. The binding of Jo2 to neither recombinant mouse Fas nor mouse hepatocytes was inhibited by an excessive amount of HFE7A. Interestingly, HFE7A bound to hepatocytes isolated from Fas knockout mice. From these results, it is suggested that HFE7A may exert a protective effect against Jo2-induced hepatitis not by competitively inhibiting the binding of Jo2 to Fas on hepatocytes, and that a distinct molecule other than Fas may possibly be involved in the protective effect of HFE7A against Jo2-induced hepatic injury. PMID:20024619

  17. Bleach Neutralizes Mold Allergens

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Researchers at National Jewish Medical and Research Center have demonstrated that dilute bleach not only kills common household mold, but may also neutralize the mold allergens that cause most mold-related health complaints. The study, published in the Journal of Allergy and Clinical Immunology, is the first to test the effect on allergic…

  18. Neutralization of electrophotographic developer

    Microsoft Academic Search

    D. A. Hays

    1977-01-01

    In many electrophotographic development systems, the developer consists of toner particles (?10 ?) triboelectrically charged by carrier beads (?100–250 ?). Since development onto a photoconductor continually removes charged toner from the development system, the carrier-bead charge would continue to increase with use unless, as happens, the developer net charge is limited by some neutralization mechanism. From a series of measurements

  19. Neutralization of electrophotographic developer

    Microsoft Academic Search

    D. A. Hays

    1977-01-01

    In many electrophotographic development systems, the developer consists of toner particles (~10 mu) triboelectrically charged by carrier beads (~100-250 mu). Since development onto a photoconductor continually removes charged toner from the development system, the carrier-bead charge would continue to increase with use unless, as happens, the developer net charge is limited by some neutralization mechanism. From a series of measurements

  20. Four families with immunodeficiency and chromosome abnormalities.

    PubMed Central

    Candy, D C; Hayward, A R; Hughes, D T; Layward, L; Soothill, J F

    1979-01-01

    Six children, with severe deficiency of some or all of the immunoglobulins and minor somatic abnormalities, had chromosomal abnormalities: (1) 45,XY,t(13q/18q), (2) 46,XY,21ps +, (3) two brothers 46,XY (inv. 7) (4) 45,X,t(11p/10p)/46X,iXq,t(11p/10p) and, (5) in addendum, 45,XX,-18;46,XX, r18. The chromosome abnormalities were detected in B- as well as T-lymphocytes (as evidenced by using both PHA- and PWM-stimulated cultures) in all probands, but one was mosaic in PHA culture, although all his PWM-stimulated cells were abnormal. Chromosomal variants were also detected in relatives of three and immunodeficiency in relatives of two. Images Fig. 1 Fig. 3 PMID:314782

  1. Acquired immunodeficiency syndrome: Ga-67 citrate imaging

    SciTech Connect

    Woolfenden, J.M.; Carrasquillo, J.A.; Larson, S.M.; Simmons, J.T.; Masur, H.; Smith, P.D.; Shelhamer, J.H.; Ognibene, F.P.

    1987-02-01

    All gallium-67 citrate scans obtained in patients with acquired immunodeficiency syndrome (AIDS) at the Clinical Center, National Institutes of Health (Bethesda, Md.) were retrospectively analyzed and correlated with the results of bronchoscopy, chest radiography, and endoscopy. There were 164 scans of 95 patients. Twenty scans were from patients with Pneumocystis carinii pneumonia; 19 were abnormal, for a sensitivity of 95%. Ga-67 uptake tended to be less in patients receiving therapy for P. carinii pneumonia. Chest radiographs were normal at least initially in three patients with abnormal scans and P. carinii pneumonia. Unusually prominent colonic activity was associated with infection in some patients. No lesions of Kaposi sarcoma showed tracer uptake. Gallium scanning is useful for detecting P. carinii pneumonia and other opportunistic infections in patients with AIDS, but it is not useful for localizing Kaposi sarcoma.

  2. Intestinal leishmaniasis in acquired immunodeficiency syndrome.

    PubMed

    Molaei, M; Minakari, M; Pejhan, Sh; Mashayekhi, R; Modaress Fatthi, A R; Zali, M R

    2011-05-01

    In endemic regions, visceral leishmaniasis is one of the most common opportunistic infections in HIV positive patients. Simultaneous infection with Leishmania and HIV has been reported in some countries but this is the first report of such a case in Iran. Our patient was a 27 years old man with intermittent night fever, abdominal pain, loss of appetite, vomiting, watery diarrhea and severe weight loss for 6 months. He had low socio-economic status with an imprisonment history. The patient was quite cachectic and had low grade fever. Physical exam and upper GI endoscopy revealed oropharyngeal candidiasis. Microscopic evaluation of duodenal biopsy material showed Leishmania amastigotes in macrophages of lamina propria. Leishman bodies were also observed in bone marrow aspiration specimen. Serologic tests were positive for Leishmania infantum. HIV antibody was also positive with a CD4+cell count of 80/?l. The diagnosis was acquired immunodeficiency syndrome with simultaneous visceral leishmaniasis involving intestinal mucosa. PMID:22737493

  3. Severe combined immunodeficiency: a national surveillance study.

    PubMed

    Yee, Anthony; De Ravin, Suk See; Elliott, Elizabeth; Ziegler, John B

    2008-06-01

    National immunodeficiency registers in several countries have reported prevalence but not incidence rates for severe combined immunodeficiency (SCID). The objective of this study was to document the incidence and type of SCID in Australia, the age and clinical features at presentation and short-term management. The Australian Paediatric Surveillance Unit conducts active, monthly, national surveillance of rare disorders with reporting by child-health specialists. Between May 1995 and December 2001, clinicians provided clinical and laboratory data on children newly diagnosed with SCID. Thirty-three incident cases of SCID were identified [incidence 1.8/10(5) live births per annum; 95% confidence interval (CI) 1.2-2.5]. Twenty-six children had classical SCID (1.45/10(5) live births; 95% CI, 0.9-2.0) and 20 (77%) of these were boys. Classical SCID was X-linked in 13 children, autosomal recessive (AR), not further classified in four, and attributed to adenosine deaminase deficiency (ADA) in four, interleukin-7 receptor alpha chain deficiency in one, Ommen syndrome in two, and Di George syndrome in two. Twenty-one (81%) received bone marrow/stem cell transplantation, three of whom died between 1 and 4 months after transplantation (two ADA deficient, one AR). Seven children had atypical SCID, five of whom died within 1-4 yr of diagnosis. Most children with SCID presented with failure to thrive and recurrent infections and there was no significant delay between presentation and diagnosis. The reported national incidence of classical SCID in Australia (1.45/10(5) or approximately 4 cases per year or 1/69,000 live births) is consistent with the rate (1.4/10(5)) previously reported in Victoria. Diagnosis is rarely delayed, and transplantation is associated with good short-term survival. PMID:18221464

  4. 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-infected subjects with cognitive and motor dysfunction. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 14 Figure 15 PMID:8780406

  5. Molecular characterization of feline immunodeficiency virus budding.

    PubMed

    Luttge, Benjamin G; Shehu-Xhilaga, Miranda; Demirov, Dimiter G; Adamson, Catherine S; Soheilian, Ferri; Nagashima, Kunio; Stephen, Andrew G; Fisher, Robert J; Freed, Eric O

    2008-03-01

    Infection of domestic cats with feline immunodeficiency virus (FIV) is an important model system for studying human immunodeficiency virus type 1 (HIV-1) infection due to numerous similarities in pathogenesis induced by these two lentiviruses. However, many molecular aspects of FIV replication remain poorly understood. It is well established that retroviruses use short peptide motifs in Gag, known as late domains, to usurp cellular endosomal sorting machinery and promote virus release from infected cells. For example, the Pro-Thr/Ser-Ala-Pro [P(T/S)AP] motif of HIV-1 Gag interacts directly with Tsg101, a component of the endosomal sorting complex required for transport I (ESCRT-I). A Tyr-Pro-Asp-Leu (YPDL) motif in equine infectious anemia virus (EIAV), and a related sequence in HIV-1, bind the endosomal sorting factor Alix. In this study we sought to identify and characterize FIV late domain(s) and elucidate cellular machinery involved in FIV release. We determined that mutagenesis of a PSAP motif in FIV Gag, small interfering RNA-mediated knockdown of Tsg101 expression, and overexpression of a P(T/S)AP-binding fragment of Tsg101 (TSG-5') each inhibited FIV release. We also observed direct binding of FIV Gag peptides to Tsg101. In contrast, mutagenesis of a potential Alix-binding motif in FIV Gag did not affect FIV release. Similarly, expression of the HIV-1/EIAV Gag-binding domain of Alix (Alix-V) did not disrupt FIV budding, and FIV Gag peptides showed no affinity for Alix-V. Our data demonstrate that FIV relies predominantly on a Tsg101-binding PSAP motif in the C terminus of Gag to promote virus release in HeLa cells, and this budding mechanism is highly conserved in feline cells. PMID:18094166

  6. Cross-protective immune responses induced in rhesus macaques by immunization with attenuated macrophage-tropic simian immunodeficiency virus.

    PubMed Central

    Clements, J E; Montelaro, R C; Zink, M C; Amedee, A M; Miller, S; Trichel, A M; Jagerski, B; Hauer, D; Martin, L N; Bohm, R P

    1995-01-01

    The simian immunodeficiency virus (SIV) macaque model of AIDS has provided a valuable system with which to investigate vaccine approaches for protection against human immunodeficiency virus type 1 (HIV-1) infection. In particular, the ability of macaques persistently infected with attenuated infectious molecular clones of SIV to resist challenge with the pathogenic parental swarm has conclusively demonstrated that protective immunity can be achieved by immunization prior to exposure. The breadth of these protective responses and the immunological correlates of protection, however, have not been identified. In addition, vaccine studies have mainly employed lymphocyte-tropic strains of HIV-1 and SIV. Recent studies have implicated macrophage-tropic strains in the transmission of HIV-1 and have suggested that these virus strains should be examined in vaccine strategies. Macrophage-tropic viruses may confer additional advantages in the induction of protective immunity by replication in antigen-presenting cells. In this study, the immune response of rhesus macaques inoculated with an attenuated macrophage-tropic recombinant of SIVmac239 (SIV/17E-Cl) was evaluated with respect to protective immunity by heterologous challenge at various times after infection. Vigorous type-specific neutralizing-antibody responses restricted to SIV/17E-Cl were evident by 2 weeks postinfection. By 7 months, however, cross-reactive neutralizing antibodies emerged which neutralized not only SIV/17E-Cl but also the heterologous primary isolate SIV/DeltaB670. Challenge of SIV/17E-Cl-infected monkeys with SIV/DeltaB670 at various times postinfection demonstrated that protective responses were associated with the appearance of cross-reactive neutralizing antibodies. Furthermore, passive transfer of sera from SIV/17E-Cl-infected animals passively protected two of four naive recipients. PMID:7707496

  7. Potent activity of 2'-beta-fluoro-2',3'-dideoxyadenosine against human immunodeficiency virus type 1 infection in hu-PBL-SCID mice.

    PubMed Central

    Ruxrungtham, K; Boone, E; Ford, H; Driscoll, J S; Davey, R T; Lane, H C

    1996-01-01

    A new antiretroviral agent, 2'-beta-fluoro-2',3'-dideoxyadenosine (FddA), is an acid-stable compound whose triphosphate form is a potent reverse transcriptase inhibitor with in vitro anti-human immunodeficiency virus (HIV) activity and a favorable pharmacokinetic profile. Severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice) provide a useful small-animal model for HIV research. In the present study we utilized this experimental system for the in vivo evaluation of the anti-HIV activity of this new compound when administered prior to infection. Initial studies revealed that, following a challenge with 50 100% tissue culture infective doses of HIV type 1 lymphadenopathy-associated virus, 39 of 42 (93%) control mice developed HIV infection, as evidenced by positive coculture or positive PCR. Administration of zidovudine decreased the infection rate to 5 of 16 (31%), while administration of FddA decreased the infection rate to 0 of 44 (0%). In follow-up controlled studies, the anti-HIV activity of FddA was confirmed, with 18 of 20 control mice showing evidence of HIV infection, compared with 4 of 20 FddA-treated mice. In addition to having direct anti-HIV effects, FddA was found to have a protective effect on human CD4+ T cells in the face of HIV infection. Mice treated with FddA were found to have a significantly higher percentage of CD4+ T cells than controls (10.3% +/- 3.4% versus 0.27% +/- 0.21%; P = 0.01). Thus, FddA, with its potent anti-HIV activity in vivo, high oral bioavailability, long intracellular half-life, and ability to preserve CD4+ cells in the presence of HIV, appears to be a promising agent for clinical investigation. PMID:8891146

  8. Lithium Jet Neutralizer to Improve Negative Ion Neutral Beam Performance

    SciTech Connect

    Grisham, L. R. [Princeton Plasma Physics Laboratory, P.O. Box 451, Princeton, New Jersey 08543 (United States)

    2009-03-12

    Fusion neutral beam systems have conventionally used gas cells of the beam isotope as neutralizers. In the design of negative ion beam systems for ITER, and likely also for future reactors, the large gas efflux arising from these cells can lead to many problems. We discuss the possibility of decreasing the gas load by using a lithium jet neutralizer, which would also afford higher neutralization efficiency.

  9. Lithium Jet Neutralizer to Improve Negative Ion Neutral Beam Performance

    NASA Astrophysics Data System (ADS)

    Grisham, L. R.

    2009-03-01

    Fusion neutral beam systems have conventionally used gas cells of the beam isotope as neutralizers. In the design of negative ion beam systems for ITER, and likely also for future reactors, the large gas efflux arising from these cells can lead to many problems. We discuss the possibility of decreasing the gas load by using a lithium jet neutralizer, which would also afford higher neutralization efficiency.

  10. 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

  11. Human immunodeficiency viruses: SIV infection in wild gorillas

    Microsoft Academic Search

    Fran van Heuverswyn; Yingying Li; Cecile Neel; Elizabeth Bailes; Brandon F. Keele; Weimin Liu; Severin Loul; Christelle Butel; Florian Liegeois; Yanga Bienvenue; Eitel Mpoudi Ngolle; Paul M. Sharp; George M. Shaw; Eric Delaporte; Beatrice H. Hahn; Martine Peeters

    2006-01-01

    Chimpanzees (Pan troglodytes troglodytes) from west central Africa are recognized as the reservoir of simian immunodeficiency viruses (SIVcpzPtt) that have crossed at least twice to humans: this resulted in the AIDS pandemic (from human immunodeficiency virus HIV-1 group M) in one instance and infection of just a few individuals in Cameroon (by HIV-1 group N) in another. A third HIV-1

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

    Microsoft Academic Search

    WOLFGANG HOFMANN; DAVID SCHUBERT; JASON LABONTE; LINDA MUNSON; SUSAN GIBSON; JONATHAN SCAMMELL; PAUL FERRIGNO; JOSEPH SODROSKI

    1999-01-01

    By using replication-defective vectors derived from human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIVmac), and murine leukemia virus (MuLV), all of which were pseudotyped with the vesicular stomatitis virus (VSV) G glycoprotein, the efficiency of postentry, early infection events was examined in target cells of several mammalian species. Titers of HIV-1 vectors were significantly lower than those of

  13. Gene Therapy for RAG-deficient Severe Combined Immunodeficiency

    Microsoft Academic Search

    K. Pike

    2007-01-01

    Severe combined immunodeficiency (SCID) is a rare \\u000aclass of primary, inherited, immunodeficiency causing infants to \\u000asuffer from persistent diarrhea, opportunistic infections and a \\u000afailure to thrive. RAG proteins play a crucial role in the initiation \\u000aof V(D)J recombination of immunoglobulin (Ig) and T-cell receptor \\u000a(TCR) gene segments. Inactivating mutations in RAG1 or RAG2 lead to a \\u000adevelopmental block at early

  14. The molecular basis of X-linked immunodeficiency disease

    Microsoft Academic Search

    C. Kinnon; R. Levinsky

    1992-01-01

    Summary The molecular bases of the X-linked immunodeficiency diseases remain largely undetermined. Two of the genes involved in these diseases have been isolated, namely the genes for X-linked chronic granulomatous disease and properdin deficiency, and substantial progress has now been made in identifying the genes which are defective in the other five diseases, Wiskott-Aldrich syndrome, X-linked severe combined immunodeficiency, X-linked

  15. Molecular and genetic basis of X-linked immunodeficiency disorders

    Microsoft Academic Search

    Jennifer M. Puck

    1994-01-01

    Summary Within a short time interval the specific gene defects causing three X-linked human immunodeficiencies, agammaglobulinemia (XLA), hyper-IgM syndrome (HIGM), and severe combined immunodeficiency (XSCID), have been identified. These represent the first human disease phenotypes associated with each of three gene families already recognized to be important in lymphocyte development and signaling: XLA is caused by mutations of a B

  16. Common variable immunodeficiency (CVID) presenting with malabsorption due to giardiasis.

    PubMed

    Onba?i, Kevser; Gün?ar, Fulya; Sin, Aytül Z; Ardeniz, Omür; Kokuluda?, Ali; Sebik, Filiz

    2005-06-01

    Common variable immunodeficiency is characterized with B-cell and T-cell dysfunction and hypogammaglobulinemia. Recurrent bacterial infections, such as otitis media, chronic sinusitis and recurrent pneumonia due to diminished immunoglobulin (Ig) levels and impaired antibody production are frequently observed in common variable immunodeficiency. Almost half of the patients with common variable immunodeficiency have problems related to the gastrointestinal system. A 39-year-old woman was referred to our department with the complaint of chronic diarrhea. She had experienced diarrhea without mucus or blood in the last year and had lost 30 kg. In her medical history, she had suffered from recurrent upper and lower respiratory infections like sinusitis, otitis media and pneumonia since childhood. Serum immunoglobulin levels were low. There were no parasites or ova in her stool examinations. Esophagogastroduodenoscopy detected widespread macroscopic nodular appearance on duodenum, and biopsies from the duodenum revealed giardiasis invading the tissue. She was diagnosed as common variable immunodeficiency. After metronidazole therapy and intravenous immunoglobulin infusion was started, her diarrhea attacks ceased and she regained her normal weight. Common gastrointestinal system problems in patients with common variable immunodeficiency are lactose intolerance, lymphoid hyperplasia/diffuse lymphoid infiltration, loss of villi and infection, especially with Giardia lamblia. Giardiasis may lead to severe mucosal flattening and sometimes to lymphoid hyperplasia at the lamina propria of the duodenum. Medical history should be evaluated carefully regarding recurrent respiratory infections. In such cases with chronic diarrhea, common variable immunodeficiency should be kept in mind as a possible cause. PMID:16252205

  17. Envelope Variants Circulating as Initial Neutralization Breadth Developed in Two HIV-Infected Subjects Stimulate Multiclade Neutralizing Antibodies in Rabbits

    PubMed Central

    Malherbe, Delphine C.; Pissani, Franco; Sather, D. Noah; Guo, Biwei; Pandey, Shilpi; Sutton, William F.; Stuart, Andrew B.; Robins, Harlan; Park, Byung; Krebs, Shelly J.; Schuman, Jason T.; Kalams, Spyros; Hessell, Ann J.

    2014-01-01

    ABSTRACT Identifying characteristics of the human immunodeficiency virus type 1 (HIV-1) envelope that are effective in generating broad, protective antibodies remains a hurdle to HIV vaccine design. Emerging evidence of the development of broad and potent neutralizing antibodies in HIV-infected subjects suggests that founder and subsequent progeny viruses may express unique antigenic motifs that contribute to this developmental pathway. We hypothesize that over the course of natural infection, B cells are programmed to develop broad antibodies by exposure to select populations of emerging envelope quasispecies variants. To test this hypothesis, we identified two unrelated subjects whose antibodies demonstrated increasing neutralization breadth against a panel of HIV-1 isolates over time. Full-length functional env genes were cloned longitudinally from these subjects from months after infection through 2.6 to 5.8 years of infection. Motifs associated with the development of breadth in published, cross-sectional studies were found in both subjects. We compared the immunogenicity of envelope vaccines derived from time points obtained during and after broadening of neutralization activity within these subjects. Rabbits were coimmunized four times with selected multiple gp160 DNAs and gp140-trimeric envelope proteins. The affinity of the polyclonal response increased as a function of boosting. The most rapid and persistent neutralization of multiclade tier 1 viruses was elicited by envelopes that were circulating in plasma at time points prior to the development of 50% neutralization breadth in both human subjects. The breadth elicited in rabbits was not improved by exposure to later envelope variants. These data have implications for vaccine development in describing a target time point to identify optimal envelope immunogens. IMPORTANCE Vaccine protection against viral infections correlates with the presence of neutralizing antibodies; thus, vaccine components capable of generating potent neutralization are likely to be critical constituents in an effective HIV vaccine. However, vaccines tested thus far have elicited only weak antibody responses and very modest, waning protection. We hypothesized that B cells develop broad antibodies by exposure to the evolving viral envelope population and tested this concept using multiple envelopes from two subjects who developed neutralization breadth within a few years of infection. We compared different combinations of envelopes from each subject to identify the most effective immunogens and regimens. In each subject, use of HIV envelopes circulating during the early development and maturation of breadth generated more-potent antibodies that were modestly cross neutralizing. These data suggest a new approach to identifying envelope immunogens that may be more effective in generating protective antibodies in humans. PMID:25210191

  18. Neutral particle beam intensity controller

    DOEpatents

    Dagenhart, W.K.

    1984-05-29

    The neutral beam intensity controller is based on selected magnetic defocusing of the ion beam prior to neutralization. The defocused portion of the beam is dumped onto a beam dump disposed perpendicular to the beam axis. Selective defocusing is accomplished by means of a magnetic field generator disposed about the neutralizer so that the field is transverse to the beam axis. The magnetic field intensity is varied to provide the selected partial beam defocusing of the ions prior to neutralization. The desired focused neutral beam portion passes along the beam path through a defining aperture in the beam dump, thereby controlling the desired fraction of neutral particles transmitted to a utilization device without altering the kinetic energy level of the desired neutral particle fraction. By proper selection of the magnetic field intensity, virtually zero through 100% intensity control of the neutral beam is achieved.

  19. Neutral Equations of Mixed Type

    E-print Network

    Lamb, Charles

    2012-12-31

    In this dissertation we consider neutral equations of mixed type. In particular, we con- sider the associated linear Fredholm theory and nerve fiber models that are written as systems of neutral equations of mixed type. ...

  20. CD4-Mimetic Small Molecules Sensitize Human Immunodeficiency Virus to Vaccine-Elicited Antibodies

    PubMed Central

    Madani, Navid; Princiotto, Amy M.; Schön, Arne; LaLonde, Judith; Feng, Yu; Freire, Ernesto; Park, Jongwoo; Courter, Joel R.; Jones, David M.; Robinson, James; Liao, Hua-Xin; Moody, M. Anthony; Permar, Sallie; Haynes, Barton; Smith, Amos B.; Wyatt, Richard

    2014-01-01

    ABSTRACT Approaches to prevent human immunodeficiency virus (HIV-1) transmission are urgently needed. Difficulties in eliciting antibodies that bind conserved epitopes exposed on the unliganded conformation of the HIV-1 envelope glycoprotein (Env) trimer represent barriers to vaccine development. During HIV-1 entry, binding of the gp120 Env to the initial receptor, CD4, triggers conformational changes in Env that result in the formation and exposure of the highly conserved gp120 site for interaction with the coreceptors, CCR5 and CXCR4. The DMJ compounds (+)-DMJ-I-228 and (+)-DMJ-II-121 bind gp120 within the conserved Phe 43 cavity near the CD4-binding site, block CD4 binding, and inhibit HIV-1 infection. Here we show that the DMJ compounds sensitize primary HIV-1, including transmitted/founder viruses, to neutralization by monoclonal antibodies directed against CD4-induced (CD4i) epitopes and the V3 region, two gp120 elements involved in coreceptor binding. Importantly, the DMJ compounds rendered primary HIV-1 sensitive to neutralization by antisera elicited by immunization of rabbits with HIV-1 gp120 cores engineered to assume the CD4-bound state. Thus, small molecules like the DMJ compounds may be useful as microbicides to inhibit HIV-1 infection directly and to sensitize primary HIV-1 to neutralization by readily elicited antibodies. IMPORTANCE Preventing HIV-1 transmission is a priority for global health. Eliciting antibodies that can neutralize many different strains of HIV-1 is difficult, creating problems for the development of a vaccine. We found that certain small-molecule compounds can sensitize HIV-1 to particular antibodies. These antibodies can be elicited in rabbits. These results suggest an approach to prevent HIV-1 sexual transmission in which a virus-sensitizing microbicide is combined with a vaccine. PMID:24696475

  1. Sensitivity of human immunodeficiency virus to bicyclam derivatives is influenced by the three-dimensional structure of gp120.

    PubMed Central

    De Vreese, K; Van Nerum, I; Vermeire, K; Anné, J; De Clercq, E

    1997-01-01

    The bicyclams are a new class of anti-human immunodeficiency virus (anti-HIV) compounds targeted at viral entry. From marker rescue experiments, it appears that the envelope gp120 glycoprotein plays an important role in the anti-HIV activity of the bicyclams. Bicyclam-resistant strains contain a number of amino acid changes scattered over the V2 to V5 region of gp120. Experiments aimed at estimating the relative importance of particular amino acid changes with regard to the overall resistance pattern are described. The sequences of some partially bicyclam-resistant virus strains, obtained during the resistance development process, were analyzed, and the corresponding 50% effective concentrations were determined. Selected mutations observed in bicyclam-resistant strains were introduced in the wild-type background by site-directed mutagenesis. In addition, some amino acids were back-mutated to their wild-type counterparts in an otherwise JM3100-resistant strain. The sensitivities of these mutant viruses to bicyclams were determined. Construction of chimeric viruses, carrying the V3 loop of JM3100-resistant virus in a wild-type HIV type 1 HXB2 background, enabled us to investigate the importance of the mutations in the V3 loop of JM3100-resistant virus. From the results described in the report, it can be concluded that single amino acid substitutions do not influence the observed resistance to JM3100. Also, the mutations in the V3 loop are not sufficient to engender even a partially resistant phenotype. We postulate that the overall conformation of gp120 determines the degree of sensitivity or resistance of HIV strains to bicyclams. PMID:9420029

  2. Neutral beams for mirrors

    SciTech Connect

    Fink, J.H.

    1983-08-31

    An important demonstration of negative ion technology is proposed for FY92 in the MFTF-..cap alpha..+T, an upgrade of the Mirror Fusion Test Facility at the Lawrence Livermore National Laboratory. This facility calls for 200-keV negative ions to form neutral beams that generate sloshing ions in the reactor end plugs. Three different beam lines are considered for this application. Their advantages and disadvantages are discussed.

  3. Antihypertensive neutral lipid

    DOEpatents

    Snyder, Fred L. (Oak Ridge, TN); Blank, Merle L. (Oak Ridge, TN)

    1986-01-01

    The invention relates to the discovery of a class of neutral acetylated ether-linked glycerolipids having the capacity to lower blood pressure in warm-blooded animals. This physiological effect is structure sensitive requiring a long chain alkyl group at the sn-1 position and a short carbon chain acyl group (acetyl or propionyl) at the sn-2 position, and a hydroxyl group at the sn-3 position.

  4. Neutral Buoyancy Simulator Test

    NASA Technical Reports Server (NTRS)

    1995-01-01

    A diver tests a secondary camera and maneuvering platform in Marshall's Neutral Buoyancy Simulator (NBS).The secondary camera will be beneficial for recording repairs and other extra vehicular activities (EVA) the astronuats will perform while making repairs on the Hubble Space Telescope (HST). The maneuvering platform was developed to give the astronauts something to stand on while performing maintenance tasks. These platforms were developed to be mobile so that the astronauts could move them to accommadate different sites.

  5. Characterization of Simian Immunodeficiency Virus SIVSM\\/Human Immunodeficiency Virus Type 2 Vpx Function in Human Myeloid Cells

    Microsoft Academic Search

    Caroline Goujon; Vanessa Arfi; Thomas Pertel; Jeremy Luban; Julia Lienard; Dominique Rigal; Jean-Luc Darlix; Andrea Cimarelli

    2008-01-01

    Human immunodeficiency virus type 2 (HIV-2)\\/simian immunodeficiency virus SIVSM Vpx is incorporated into virion particles and is thus present during the early steps of infection, when it has been reported to influence the nuclear import of viral DNA. We recently reported that Vpx promoted the accumulation of full-length viral DNA following the infection of human monocyte-derived dendritic cells (DCs). This

  6. Inhibition of human immunodeficiency virus type 1 (HIV-1) nuclear import via Vpr-Importin {alpha} interactions as a novel HIV-1 therapy

    SciTech Connect

    Suzuki, Tatsunori [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Yamamoto, Norio [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Department of General Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Nonaka, Mizuho; Hashimoto, Yoshie; Matsuda, Go; Takeshima, Shin-nosuke [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Matsuyama, Megumi; Igarashi, Tatsuhiko; Miura, Tomoyuki [Institute for Virus Research, Kyoto University, Kyoto 606-8507 (Japan); Tanaka, Rie; Kato, Shingo [Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582 (Japan); Aida, Yoko [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)], E-mail: aida@riken.jp

    2009-03-20

    The development of multidrug-resistant viruses compromises the efficacy of anti-human immunodeficiency virus (HIV) therapy and limits treatment options. Therefore, new targets that can be used to develop novel antiviral agents need to be identified. One such target is the interaction between Vpr, one of the accessory gene products of HIV-1 and Importin {alpha}, which is crucial, not only for the nuclear import of Vpr, but also for HIV-1 replication in macrophages. We have identified a potential parent compound, hematoxylin, which suppresses Vpr-Importin {alpha} interaction, thereby inhibiting HIV-1 replication in a Vpr-dependent manner. Analysis by real-time PCR demonstrated that hematoxylin specifically inhibited nuclear import step of pre-integration complex. Thus, hematoxylin is a new anti-HIV-1 inhibitor that targets the nuclear import of HIV-1 via the Vpr-Importin {alpha} interaction, suggesting that a specific inhibitor of the interaction between viral protein and the cellular factor may provide a new strategy for HIV-1 therapy.

  7. Diagnostics of fast neutral beams

    Microsoft Academic Search

    Alok Ranjan

    2008-01-01

    As device dimensions continue to shrink, charging damage during reactive ion etching (RIE) has become a serious concern. Fast neutral beams with energies of tens to hundreds of eV may be useful for mitigating charging damage. For neutral beam processing to be viable, however, the beam energy, flux and directionality must be comparable to those in RIE. Characterization of neutral

  8. Neutrality between Government and Religion.

    ERIC Educational Resources Information Center

    Mawdsley, Ralph D.

    1996-01-01

    The overall guiding principle of neutrality between government and religion masks a tension that exists between free exercise of religion and establishment of religion. Reviews the development and current status of "Lemon" as a test for neutrality; proposes a new test for neutrality, evenhandedness, that is common to both the Free Exercise and…

  9. Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01

    SciTech Connect

    Zhou, Tongqing; Georgiev, Ivelin; Wu, Xueling; Yang, Zhi-Yong; Dai, Kaifan; Finzi, Andrés; Kwon, Young Do; Scheid, Johannes F.; Shi, Wei; Xu, Ling; Yang, Yongping; Zhu, Jiang; Nussenzweig, Michel C.; Sodroski, Joseph; Shapiro, Lawrence; Nabel, Gary J.; Mascola, John R.; Kwong, Peter D. (NIH); (Rockefeller); (DFCI)

    2010-08-26

    During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.

  10. Elimination of nonspecific cytomegalovirus immunoglobulin M activities in the enzyme-linked immunosorbent assay by using anti-human immunoglobulin G.

    PubMed Central

    Joassin, L; Reginster, M

    1986-01-01

    Direct enzyme-linked immunosorbent assay methods offer several advantages in assessing past or recent exposure to cytomegalovirus (CMV) infection, but there persist many pitfalls in the use of these methods for determining specific immunoglobulin M (IgM). The efficiency of absorption of sera by IgG-coated latex beads, aggregated human IgG, or Staphylococcus aureus, i.e., for removing nonspecific CMV IgM activities, was evaluated in comparison with the effect of an anti-human IgG hyperimmune serum. Large routine series comprising serum samples from patients of various clinical groups and healthy individuals were examined. The CMV IgM-positive samples were at first treated with latex or aggregated IgG, but these absorptions left too many CMV IgM-positive individuals. S. aureus increased the nonspecific activity of some sera and, in other cases, removed or impaired specific IgM activities. The anti-IgG treatment caused the disappearance of nonspecific CMV IgM activities that had resisted the other treatments, whereas specific activities remained intact. Utilizing this method, only 1.03% of the routine series patients remained CMV IgM positive by the enzyme-linked immunosorbent assay, a figure in good agreement with a mean probability of CMV antibody acquisition of 0.33% for the population living in Belgium. On the other hand, in a series of patients who were investigated for serological response to several viruses, eight individuals displayed multiple IgM activities after anti-IgG treatment. In these cases, most IgM activities were found in patients who had IgG toward the related antigen for a long time before transient IgM was detected. This result implies that to assess a diagnosis of primary infection, it is necessary to examine serial specimens for IgG acquisition accompanying specific IgM. PMID:3007570

  11. Polarographic direct determination and homogeneous immunoassay of anti-human serum albumin (HSA) by parallel catalytic hydrogen wave of anti-HSA or HSA.

    PubMed

    Song, Jun-Feng; Liu, Yang-Qin; Guo, Wei

    2003-03-15

    Human serum albumin (HSA) or anti-human serum albumin (anti-HSA) yields a catalytic hydrogen wave at about -1.85V (vs Ag/AgCl) in 0.25M NH(3).H(2)O-NH(4)Cl (pH 8.58) buffer. When 1.0 x 10(-2)M K(2)S(2)O(8) is present, the catalytic hydrogen wave is further catalyzed, producing a parallel catalytic wave of hydrogen as catalyst in nature, termed the parallel catalytic hydrogen wave. The sensitivity of the parallel catalytic hydrogen wave is higher by two orders of magnitude than that of the catalytic hydrogen wave. Using the parallel catalytic hydrogen wave of anti-HSA or HSA in the presence of K(2)S(2)O(8), two sensitive methods for the determination of anti-HSA were developed. One is a direct determination based on the parallel catalytic hydrogen wave of anti-HAS itself, and the other is a homogeneous immunoassay based on measuring the decrease of the peak current of the parallel catalytic hydrogen wave of HSA after homogeneous immunoreaction of HSA with anti-HSA. In the direct determination, the second-order derivative peak current of the parallel catalytic hydrogen wave of anti-HSA itself is rectilinear to its titer in the range from 1:1.0 x 10(7) to 1:8.4 x 10(6). In the homogeneous immunoassay, the decrease in the second-order derivative peak current of the parallel catalytic hydrogen wave of HSA is linearly related to the added anti-HSA in the titer range from 1:3.0 x 10(7) to 1:6.0 x 10(6). These assays are highly sensitive and rapid in operation and can be used to evaluate such antigens and their antibodies as those that could yield the parallel catalytic hydrogen wave. PMID:12654307

  12. A fusion intermediate gp41 immunogen elicits neutralizing antibodies to HIV-1.

    PubMed

    Lai, Rachel P J; Hock, Miriam; Radzimanowski, Jens; Tonks, Paul; Hulsik, David Lutje; Effantin, Gregory; Seilly, David J; Dreja, Hanna; Kliche, Alexander; Wagner, Ralf; Barnett, Susan W; Tumba, Nancy; Morris, Lynn; LaBranche, Celia C; Montefiori, David C; Seaman, Michael S; Heeney, Jonathan L; Weissenhorn, Winfried

    2014-10-24

    The membrane-proximal external region (MPER) of the human immunodeficiency virus, type 1 (HIV-1) envelope glycoprotein subunit gp41 is targeted by potent broadly neutralizing antibodies 2F5, 4E10, and 10E8. These antibodies recognize linear epitopes and have been suggested to target the fusion intermediate conformation of gp41 that bridges viral and cellular membranes. Anti-MPER antibodies exert different degrees of membrane interaction, which is considered to be the limiting factor for the generation of such antibodies by immunization. Here we characterize a fusion intermediate conformation of gp41 (gp41(int)-Cys) and show that it folds into an elongated ? 12-nm-long extended structure based on small angle x-ray scattering data. Gp41(int)-Cys was covalently linked to liposomes via its C-terminal cysteine and used as immunogen. The gp41(int)-Cys proteoliposomes were administered alone or in prime-boost regimen with trimeric envelope gp140(CA018) in guinea pigs and elicited high anti-gp41 IgG titers. The sera interacted with a peptide spanning the MPER region, demonstrated competition with broadly neutralizing antibodies 2F5 and 4E10, and exerted modest lipid binding, indicating the presence of MPER-specific antibodies. Although the neutralization potency generated solely by gp140(CA018) was higher than that induced by gp41(int)-Cys, the majority of animals immunized with gp41(int)-Cys proteoliposomes induced modest breadth and potency in neutralizing tier 1 pseudoviruses and replication-competent simian/human immunodeficiency viruses in the TZM-bl assay as well as responses against tier 2 HIV-1 in the A3R5 neutralization assay. Our data thus demonstrate that liposomal gp41 MPER formulation can induce neutralization activity, and the strategy serves to improve breadth and potency of such antibodies by improved vaccination protocols. PMID:25160627

  13. Reduced intensity transplantation for primary immunodeficiency disorders.

    PubMed

    Veys, Paul

    2011-06-22

    Studies so far indicate that reduced intensity transplantation (RIT) may have an important role in treating patients with primary immunodeficiency disease (PID). Unlike more standard approaches, such regimens can be used without severe toxicity in patients with severe pulmonary or hepatic disease. RIT also offers the advantage that long-term sequelae such as infertility or growth retardation may be avoided or reduced. RIT appears to be most appropriate for those patients with significant co-morbidities (eg T cell deficiencies) and those undergoing unrelated donor haematopoietic cell transplantation. More studies are required using pharmacokinetic monitoring (eg busulphan, treosulfan and alemtuzumab) and varying stem cell sources to optimise graft vs marrow reactions and minimise graft vs host disease. In certain PID patients RIT will be the "first step" towards establishing donor cell engraftment; second infusions of donor stem cells, donor lymphocyte infusions, or a second myeloablative HCT, which appears to be well tolerated, may be required in some patients with low level donor chimerism or graft rejection. PMID:22053273

  14. 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

  15. Immunodeficiency and laser magnetic therapy in urology

    NASA Astrophysics Data System (ADS)

    Maati, Moufagued; Rozanov, Vladimir V.; Avdoshin, V. P.

    1996-11-01

    The importance of immunodeficiency problem has increased last time not only due to AIDS appearance, but also to a great extent as a result of the development and active practical use of the methods of immunology parameters investigations. Al great pharmaceutical firms are organizing the process of creating the drugs, influencing on the different phases of immunity, but unfortunately, the problem of their adverse effect and connected complications is till today a milestone. A great number of investigations, proving a good effect of laser-magnetic therapy concerning immune system have been done today. There is, in particular, changing of blood counts and immunologic tests after intravenous laser irradiation of blood. Intravenous laser irradiation of blood results in increasing of lymphocytes, T-immuno stimulation, stabilization of t-lymphocyte subpopulation, increasing of t-lymphocyte helper activity and decreasing of suppressor one.Under this laser action number of circulating immune complexes is decreased, and blood serum bactericide activity and lisozyme number are increased.

  16. The acquired immunodeficiency syndrome: an ultrastructural study.

    PubMed

    Sidhu, G S; Stahl, R E; el-Sadr, W; Cassai, N D; Forrester, E M; Zolla-Pazner, S

    1985-04-01

    Blood and a variety of tissues from 97 patients with the acquired immunodeficiency syndrome (AIDS) and 25 with the AIDS prodrome were studied ultrastructurally. Tubuloreticular structures (TRS) were found in 85 per cent of the patients with AIDS and in 92 per cent of those with the prodrome. Test tube and ring-shaped forms (TRF), found in 41 per cent of the patients with AIDS and in 8 per cent of those with the prodrome, increased with disease progression. Among the patients with AIDS, as the number of sites examined per case increased, the incidence of TRS and TRF tended to approach 100 per cent, suggesting that they are present in all patients with AIDS. Other changes seen frequently were immunologic capping of blood lymphocytes, intramitochondrial iron in blood reticulocytes and marrow normoblasts, megakaryocytic immaturity and platelet phagocytosis, collections of membranous rings in hepatocytic cytoplasm, suggestive of non-A, non-B hepatitis, and proliferations and engorgement of hepatic Ito cells with lipid. The data suggest that TRS and TRF can be used as diagnostic and prognostic markers. PMID:3872253

  17. Common Variable Immunodeficiency: Etiological and Treatment Issues

    PubMed Central

    Deane, Sean; Selmi, Carlo; Naguwa, Stanley M.; Teuber, Suzanne S.; Gershwin, M. Eric

    2009-01-01

    One of the great advances in clinical medicine was the recognition of the pleomorphism of the immune response and the multiple afferent and efferent limbs of antigen processing and responsiveness. A significant contribution to this understanding was derived from studies of human immunodeficiency states, including both inherited and acquired syndromes. Amongst these syndromes, one of the most common, and least understood, is common variable immune deficiency (CVID). CVID is a syndrome that leads to a reduction in serum immunoglobulins and complications including recurrent infections. Management includes immunoglobulin replacement therapy; however, patients with CVID are at risk for complications of exogenous immunoglobulin administration as well as CVID-associated diseases such as autoimmune processes and malignancies. To assess the current state of knowledge in the field, we performed a literature review of a total of 753 publications covering the period of 1968 until 2008. From this list, 189 publications were selected for discussion. In this review, we demonstrate that while the molecular basis of CVID in many cases remains incompletely understood, significant strides have been made and it is now clear that there is involvement of several pathways of immune activation, with contributions from both T and B cells. Furthermore, despite the current gaps in our knowledge of the molecular pathogenesis of the syndrome, there have been dramatic advances in management that have led to improved survival and significantly reduced morbidity in affected patients. PMID:19571563

  18. How I treat severe combined immunodeficiency.

    PubMed

    Gaspar, H Bobby; Qasim, Waseem; Davies, E Graham; Rao, Kanchan; Amrolia, Persis J; Veys, Paul

    2013-11-28

    Severe combined immunodeficiency (SCID) arises from different genetic defects associated with lymphocyte development and function and presents with severe infections. Allogeneic hematopoietic stem cell transplantation is an extremely effective way of restoring immunity in these individuals. Numerous multicenter studies have identified the factors determining successful outcome, and survival for SCID has shown great improvement. Advances in understanding the genetic basis of disease also mean that we increasingly tailor transplant protocols to the specific SCID form. Wherever possible, we attempt to transplant SCID patients without the use of cytoreductive conditioning, but it is clear that this is only successful for specific SCID forms and, although survival is good, in specific patients there are ongoing humoral defects. We aim to use matched related and unrelated donors (including cord blood) whenever possible and have limited the use of mismatched haploidentical donors. The development of autologous hematopoietic stem cell gene therapy provides another treatment of the X-linked and adenosine deaminase-deficient forms of SCID, and we discuss how we have integrated gene therapy into our treatment strategy. These developments together with the advent of universal newborn screening for SCID should allow for a highly favorable outcome for this otherwise lethal condition. PMID:24113871

  19. The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells

    PubMed Central

    Gupta, Sandeep; Gach, Johannes S.; Becerra, Juan C.; Phan, Tran B.; Pudney, Jeffrey; Moldoveanu, Zina; Joseph, Sarah B.; Landucci, Gary; Supnet, Medalyn Jude; Ping, Li-Hua; Corti, Davide; Moldt, Brian; Hel, Zdenek; Lanzavecchia, Antonio; Ruprecht, Ruth M.; Burton, Dennis R.; Mestecky, Jiri; Anderson, Deborah J.; Forthal, Donald N.

    2013-01-01

    The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown. Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody. We found that the combination of acidic pH and Env-specific IgG, including that from cervicovaginal and seminal fluids of HIV-1-infected individuals, augmented transcytosis across epithelial cells as much as 20-fold compared with Env-specific IgG at neutral pH or non-specific IgG at either pH. Enhanced transcytosis was observed with clinical HIV-1 isolates, including transmitted/founder strains, and was eliminated in Fc neonatal receptor (FcRn)-knockdown epithelial cells. Non-neutralizing antibodies allowed similar or less transcytosis than neutralizing antibodies. However, the ratio of total:infectious virus was higher for neutralizing antibodies, indicating that they allowed transcytosis while blocking infectivity of transcytosed virus. Immunocytochemistry revealed abundant FcRn expression in columnar epithelia lining the human endocervix and penile urethra. Acidity and Env-specific IgG enhance transcytosis of virus across epithelial cells via FcRn and could facilitate translocation of virus to susceptible target cells following sexual exposure. PMID:24278022

  20. Characteristics and clinical significance of a stabilization assay to detect specific antibodies to reverse transcriptase of human immunodeficiency virus.

    PubMed Central

    Morita, M; Suzuki, T; Nakajima, K; Shiozawa, C; Gill, M J; Hoshino, H

    1995-01-01

    Antibodies against reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) have been detected in seropositive subjects by immunoprecipitation, Western immunoblotting, and neutralization assay. Recently, we noticed that the antibodies against RT stabilized RT upon heat inactivation, and we have developed a stabilization assay of RT antibody. Briefly, the RT of HIV-1 is completely inactivated by incubation at 56 degrees C for 20 min, but this inactivation is inhibited in the presence of a specific antibody directed against this molecule. We examined the specificity and clinical significance of this stabilization assay. HIV-1 antibody-positive sera stabilized HIV-1 RT but not HIV-2 RT, whereas half of these sera cross-neutralized HIV-2 RT. Antibody titers against RT determined by the neutralization assay and the stabilization assay were compared with clinical characteristics. Antibodies against HIV-1 RT were much more frequently detected by the stabilization assay than by the neutralization assay. Statistically significant associations were found between stabilizing antibody titer and CD4+ cell number in peripheral blood of patients and also between antibody titer and CD4+/CD8+ ratios. These results indicate that our new stabilization assay to detect specific antibodies against RT of HIV-1 is useful as a clinical marker of infection and progress of the disease. PMID:8548538

  1. Role of a Putative gp41 Dimerization Domain in Human Immunodeficiency Virus Type 1 Membrane Fusion

    SciTech Connect

    Liu, J.; Deng, Y; Li, Q; Dey, A; Moore, J; Lu, M

    2010-01-01

    The entry of human immunodeficiency virus type 1 (HIV-1) into a target cell entails a series of conformational changes in the gp41 transmembrane glycoprotein that mediates the fusion of the viral and target cell membranes. A trimer-of-hairpins structure formed by the association of two heptad repeat (HR) regions of the gp41 ectodomain has been implicated in a late step of the fusion pathway. Earlier native and intermediate states of the protein are postulated to mediate the antiviral activity of the fusion inhibitor enfuvirtide and of broadly neutralizing monoclonal antibodies (NAbs), but the details of these structures remain unknown. Here, we report the identification and crystal structure of a dimerization domain in the C-terminal ectodomain of gp41 (residues 630 to 683, or C54). Two C54 monomers associate to form an asymmetric, antiparallel coiled coil with two distinct C-terminal {alpha}-helical overhangs. This dimer structure is conferred largely by interactions within a central core that corresponds to the sequence of enfuvirtide. The mutagenic alteration of the dimer interface severely impairs the infectivity of Env-pseudotyped viruses. Moreover, the C54 structure binds tightly to both the 2F5 and 4E10 NAbs and likely represents a potential intermediate conformation of gp41. These results should enhance our understanding of the molecular basis of the gp41 fusogenic structural transitions and thereby guide rational, structure-based efforts to design new fusion inhibitors and vaccine candidates intended to induce broadly neutralizing antibodies.

  2. Neutral beam injection system

    SciTech Connect

    Duesing, G.; Altmann, H.; Falter, H.; Goede, A.; Haange, R.; Hemsworth, R.S.; Kupschus, P.; Stork, D.; Thompson, E.

    1987-01-01

    The development of the neutral injection (NI) system for the Joint European Torus and its status in 1985 are reported. First the system parameters are discussed and the layout is described, followed by a summary of the physics design calculations, the development, production, and testing of the components and the subsystem assembly. The system commissioning is presented, including a description of the function and the realization of the NI test bed. A summary of performance predictions for 80-keV beam heating experiments, and of the experimental evidence on balanced versus coinjection, is presented. The operational experience with the first injector and the plasma physics results obtained so far are summarized.

  3. Pulsed field sample neutralization

    DOEpatents

    Appelhans, Anthony D. (Idaho Falls, ID); Dahl, David A. (Idaho Falls, ID); Delmore, James E. (Idaho Falls, ID)

    1990-01-01

    An apparatus and method for alternating voltage and for varying the rate of extraction during the extraction of secondary particles, resulting in periods when either positive ions, or negative ions and electrons are extracted at varying rates. Using voltage with alternating charge during successive periods to extract particles from materials which accumulate charge opposite that being extracted causes accumulation of surface charge of opposite sign. Charge accumulation can then be adjusted to a ratio which maintains a balance of positive and negative charge emission, thus maintaining the charge neutrality of the sample.

  4. Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection

    PubMed Central

    MacDuff, Donna A; Reese, Tiffany A; Kimmey, Jacqueline M; Weiss, Leslie A; Song, Christina; Zhang, Xin; Kambal, Amal; Duan, Erning; Carrero, Javier A; Boisson, Bertrand; Laplantine, Emmanuel; Israel, Alain; Picard, Capucine; Colonna, Marco; Edelson, Brian T; Sibley, L David; Stallings, Christina L; Casanova, Jean-Laurent; Iwai, Kazuhiro; Virgin, Herbert W

    2015-01-01

    Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine ?-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies. DOI: http://dx.doi.org/10.7554/eLife.04494.001 PMID:25599590

  5. Frequent Transmission of Immunodeficiency Viruses among Bobcats and Pumas?

    PubMed Central

    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. PMID:17670835

  6. Frequent transmission of immunodeficiency viruses among bobcats and pumas.

    PubMed

    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

    2007-10-01

    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. PMID:17670835

  7. Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection.

    PubMed

    MacDuff, Donna A; Reese, Tiffany A; Kimmey, Jacqueline M; Weiss, Leslie A; Song, Christina; Zhang, Xin; Kambal, Amal; Duan, Erning; Carrero, Javier A; Boisson, Bertrand; Laplantine, Emmanuel; Israel, Alain; Picard, Capucine; Colonna, Marco; Edelson, Brian T; Sibley, L David; Stallings, Christina L; Casanova, Jean-Laurent; Iwai, Kazuhiro; Virgin, Herbert W

    2015-01-01

    Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine ?-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies. PMID:25599590

  8. Genetics Home Reference: T-cell immunodeficiency, congenital alopecia, and nail dystrophy

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > T-cell immunodeficiency, congenital alopecia, and nail dystrophy On this ... Glossary definitions Reviewed August 2014 What is T-cell immunodeficiency, congenital alopecia, and nail dystrophy? T-cell ...

  9. Absence of porcine interferon alpha secreting cells in severe combined immunodeficiency (SCID) mice

    E-print Network

    Paris-Sud XI, Université de

    Short note Absence of porcine interferon alpha secreting cells in severe combined immunodeficiency (SCID) mice inoculated with porcine leukocytes Igor Šplíchal Ji&jadnr;í Šinkoraa Zuzana of NIPC, severe combined immunodeficiency (SCID) mice were reconstituted with porcine leukocyte

  10. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. 866...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification . The in vitro HIV drug resistance genotype assay...

  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

    ...Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis...Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis...for reducing unexpected transmission of HIV, HBV and HCV from deceased and living...

  12. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. 866...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification . The in vitro HIV drug resistance genotype assay...

  13. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. 866...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification . The in vitro HIV drug resistance genotype assay...

  14. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. 866...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay...

  15. 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...Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis...for reducing unexpected transmission of HIV, HBV and HCV from deceased and living...

  16. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. 866...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification . The in vitro HIV drug resistance genotype assay...

  17. A significant role for anti-human leukocyte antigen antibodies and antibody-mediated rejection in the biopsy-for-cause population.

    PubMed

    Banasik, M; Ko?cielska-Kasprzak, K; Myszka, M; Bartoszek, D; Zabi?ska, M; Boraty?ska, M; Kami?ska, D; Mazanowska, O; Zmonarski, S; Krajewska, M; Ha?o?, A; Dawiskiba, T; Nowakowska, B; Klinger, M

    2014-10-01

    The role of anti-human leukocyte antigen (HLA) antibodies and antibody-mediated rejection is well known, but our comprehension and the preventive measures we take seem to be insufficient. One of the major causes of premature renal transplant loss is recepients' immunologic hyperactivity to donors' antigens. Monitoring of humoral alloreactivity gives hope for early diagnosis and adequate therapy. The goal of our analysis was the assessment of the influence of anti-HLA antibodies on the function and survival of transplants. In our study we included 60 consecutive renal transplant recipients who had a renal transplant biopsy-for-cause performed due to insufficiency. Transplant biopsies were performed between the 7th day and 12th year (median, 2 years) after transplantation. Anti-HLA antibodies were present in 20 patients (33%). The patients were divided into 2 groups according the presence of anti-HLA antibodies. In a 12-month observation, 10/20 (50%) patients in the anti-HLA(+) group returned to dialysis in contrast with 7/40 (17.5%; P = .014) in the anti-HLA(-) group. Also, 8/10 (80%) of the anti-HLA(+) patients who lost the transplant had anti-HLA Abs class II and only 2/10 (20%) had anti-HLA Abs class I. Anti-HLA antibodies were specific to a donor (donor-specific antibodies [DSA]) in 8/10 (80%) of the patients who lost the transplant. Anti-HLA antibodies appeared de novo in 50% of patients who lost the transplant. Nonadherence was suspected in 50% of patients. Acute humoral rejection occurred in 1 patient. Also, 8/10 (90%) developed chronic active humoral rejection. Our study revealed that graft loss in the renal transplant biopsy-for-cause population with the presence of anti-HLA Abs during a 12-month observation reached 50%. Nonadherence in these patients was very high and amounted to 50%. Monitoring of renal transplant recipients and individualization of therapy considering humoral activity should prolong renal graft survival. PMID:25380878

  18. Antifungal prophylaxis during neutropenia and immunodeficiency.

    PubMed Central

    Lortholary, O; Dupont, B

    1997-01-01

    Fungal infections represent a major source of morbidity and mortality in patients with almost all types of immunodeficiencies. These infections may be nosocomial (aspergillosis) or community acquired (cryptococcosis), or both (candidiasis). Endemic mycoses such as histoplasmosis, coccidioidomycosis, and penicilliosis may infect many immunocompromised hosts in some geographic areas and thereby create major public health problems. With the wide availability of oral azoles, antifungal prophylactic strategies have been extensively developed. However, only a few well-designed studies involving strict criteria have been performed, mostly in patients with hematological malignancies or AIDS. In these situations, the best dose and duration of administration of the antifungal drug often remain to be determined. In high-risk neutropenic or bone marrow transplant patients, fluconazole is effective for the prevention of superficial and/or systemic candidal infections but is not always able to prolong overall survival and potentially selects less susceptible or resistant Candida spp. Primary prophylaxis against aspergillosis remains investigative. At present, no standard general recommendation for primary antifungal prophylaxis can be proposed for AIDS patients or transplant recipients. However, for persistently immunocompromised patients who previously experienced a noncandidal systemic fungal infection, prolonged suppressive antifungal therapy is often indicated to prevent a relapse. Better strategies for controlling immune deficiencies should also help to avoid some potentially life-threatening deep mycoses. When prescribing antifungal prophylaxis, physicians should be aware of the potential emergence of resistant strains, drug-drug interactions, and the cost. Well-designed, randomized, multicenter clinical trials in high-risk immunocompromised hosts are urgently needed to better define how to prevent severe invasive mycoses. PMID:9227863

  19. Nodular Regenerative Hyperplasia in Common Variable Immunodeficiency

    PubMed Central

    Fuss, Ivan J.; Friend, Julia; Yang, Zhiqong; He, Ping; Hooda, Lubna; Boyer, James; Xi, Liqiang; Raffeld, Mark; Kleiner, David E.; Heller, Theo; Strober, Warren

    2013-01-01

    Purpose Patients with Common Variable Immunodeficiency (CVID) are subject to the development of a liver disease syndrome known as nodular regenerative hyperplasia (NRH). The purpose of this study was to define the characteristics and course of this complication of CVID. Methods CVID patients were evaluated by retrospective and prospective clinical course review. Liver biopsy specimens were evaluated for evidence of NRH and studied via RT-PCR for cytokine analysis. Results NRH in our CVID patient population occurred in approximately 5% of the 261 patients in our total CVID study group, initially presenting in most cases with an elevated alkaline phosphatase level. While in some patients the disease remained static, in a larger proportion a more severe disease developed characterized by portal hypertension, the latter leading to hypersplenism with neutropenia and thrombocytopenia and, in some cases, to ascites. In addition, a substantial proportion of patients either developed or presented initially with an autoimmune hepatitis-like (AIH-like) liver disease that resulted in severe liver dysfunction and, in most cases to death due to infections. The liver histologic findings in these AIH-like patients were characterized by underlying NRH pattern with superimposed interface hepatitis, lymphocytic infiltration and fibrosis. Immunologic studies of biopsies of NRH patients demonstrated the presence of infiltrating T cells producing IFN-?, suggesting that the NRH is due to an autoimmune process. Conclusion Overall, these studies provide evidence that NRH may not be benign but, can be a severe and potentially fatal disease complication of CVID that merits close monitoring and intervention. PMID:23420139

  20. Absence of cytotoxic antibody to human immunodeficiency virus-infected cells in humans and its induction in animals after infection or immunization with purified envelope glycoprotein gp120

    SciTech Connect

    Nara, P.L.; Robey, W.G.; Gonda, M.A.; Carter, S.G.; Fischinger, P.J.

    1987-06-01

    The presence of antibody-dependent complement-mediated cytotoxicity (ACC) was assessed in humans and chimpanzees, which are capable of infection with human immunodeficiency virus isolate HTLV-IIIb, and examined in the goat after immunization with the major viral glycoprotein (gp120) of HTLV-IIIb. In infected humans no antibody mediating ACC was observed regardless of the status of disease. Even healthy individuals with high-titer, broadly reactive, neutralizing antibodies has no ACC. In contrast, chimpanzees infected with HTLV-IIIb, from whom virus could be isolated, not only had neutralizing antibody but also antibodies broadly reactive in ACC, even against distantly related human immunodeficiency virus isolates, as well as against their own reisolated virus. In the goat, the gp120 of HTLV-IIIb induced a highly type-specific response as measured by both ACC and flow cytofluorometry of live infected H9 cells. Normal human cells were not subject to ACC by animal anti-HTLV-III gp120-specific sera. Induction of ACC and neutralizing antibody were closely correlated in the animal experimental models but not in humans. The presence of ACC in gp120-inoculated goats and HTLV-III-infected chimpanzees represent a qualitative difference that may be important in the quest for the elicitation of a protective immunity in humans.

  1. Neutral Evolution of Mutational Robustness

    NASA Astrophysics Data System (ADS)

    van Nimwegen, Erik; Crutchfield, James P.; Huynen, Martijn

    1999-08-01

    We introduce and analyze a general model of a population evolving over a network of selectively neutral genotypes. We show that the population's limit distribution on the neutral network is solely determined by the network topology and given by the principal eigenvector of the network's adjacency matrix. Moreover, the average number of neutral mutant neighbors per individual is given by the matrix spectral radius. These results quantify the extent to which populations evolve mutational robustness--the insensitivity of the phenotype to mutations--and thus reduce genetic load. Because the average neutrality is independent of evolutionary parameters--such as mutation rate, population size, and selective advantage--one can infer global statistics of neutral network topology by using simple population data available from in vitro or in vivo evolution. Populations evolving on neutral networks of RNA secondary structures show excellent agreement with our theoretical predictions.

  2. Possible transmission of human immunodeficiency virus-1 infection from an elite controller to a patient who progressed to acquired immunodeficiency syndrome: a case report

    PubMed Central

    2012-01-01

    Introduction Most individuals infected with human immunodeficiency virus-1, in the absence of antiretroviral therapy, exhibit persistent virus replication and declining CD4+ cell numbers, and progress to acquired immunodeficiency syndrome within 10?years of infection. Elite controllers are rare individuals with human immunodeficiency virus-1 infection who can maintain undetectable plasma virus levels and remain asymptomatic without antiretroviral therapy. It has been proposed that elite controllers benefit from being infected with attenuated human immunodeficiency virus-1 variants. Case presentation A 31-year-old African woman presented with human immunodeficiency virus-1 infection during pregnancy and was diagnosed with acquired immunodeficiency syndrome. Subsequently, her husband, a 31-year-old African man, was tested and found to be seropositive for human immunodeficiency virus-1. His plasma human immunodeficiency virus-1 ribonucleic acid level was found to be below the limit of detection of the clinical assay. Conclusion This report provides evidence for the first described case of human immunodeficiency virus-1 infection possibly transmitted from an elite controller to a patient who progressed to acquired immunodeficiency syndrome. This observation strengthens the case against avirulence as a mechanism that protects elite controllers. PMID:22967353

  3. Late Onset Combined Immunodeficiency Presenting with Recurrent Pneumocystis jiroveci Pneumonia

    PubMed Central

    Baraboutis, Ioannis G.; Karnesis, Lazaros

    2014-01-01

    Late onset combined immunodeficiency (LOCID) is a recently described variant of common variable immunodeficiency (CVID), involving adult patients presenting with opportunistic infections and/or low CD4+ lymphocyte counts. A 36-year-old male with unremarkable past medical history presented with fever, respiratory failure, and lymphocytopenia. He was found to have Pneumocystis jiroveci pneumonia (PJP), subsequently complicated by recurrent hospital-acquired Pseudomonas aeruginosa pneumonia and immune reconstitution phenomena, attributed to restoration of immunoglobulin levels. Clinicians should be aware of LOCID, which could be confused with HIV infection/AIDS or idiopathic CD4 lymphocytopenia. In the English bibliography there is only one case report, where PJP was the initial presentation of CVID (that case would probably be classified as LOCID). Phenomena of immune reconstitution are described in various settings, including primary immunodeficiency, manifesting as temporary clinical and radiologic deterioration and leading to misperceptions of therapeutic failure and/or presence of alternative/additional diagnoses. PMID:24799913

  4. [Combined immunodeficiency with cutaneous manifestations associated with DOCK8 mutation].

    PubMed

    Cantisano, Claudio; Díaz, Héctor; Balbaryski, Jeanette; Oleastro, Matías; Quiroz, Héctor; Gaddi, Eduardo

    2014-08-01

    Different primary immunodeficiencies present increased levels of IgE and cutaneous infections of viral etiology. We report a case of a 2 y, 8 m old boy with combined immunodeficiency, dermatitis and disseminated molluscum contagiosum. The patient presented high titers of IgE, eosinophilia and pronounced TCD8 lymphopenia. Impaired proliferation assays and abnormal antibody response to vaccination were found. Normal results of ZAP-70 protein, NK function, and HLA I levels, to test quantitatives and functional defects of cytotoxic cells, lead us to suspect a mutation in DOCK8 gene. Positive result in molecular study together with clinical and immunology features in the patient confirmed the diagnosis of this new immunodeficiency, being to the authors' knowledge the first case recorded in a paediatric hospital in our country. PMID:24955914

  5. 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

  6. Immunodeficiency and autoimmune enterocolopathy linked to NFAT5 haploinsufficiency.

    PubMed

    Boland, Brigid S; Widjaja, Christella E; Banno, Asoka; Zhang, Bing; Kim, Stephanie H; Stoven, Samantha; Peterson, Michael R; Jones, Marilyn C; Su, H Irene; Crowe, Sheila E; Bui, Jack D; Ho, Samuel B; Okugawa, Yoshinaga; Goel, Ajay; Marietta, Eric V; Khosroheidari, Mahdieh; Jepsen, Kristen; Aramburu, Jose; López-Rodríguez, Cristina; Sandborn, William J; Murray, Joseph A; Harismendy, Olivier; Chang, John T

    2015-03-15

    The link between autoimmune diseases and primary immunodeficiency syndromes has been increasingly appreciated. Immunologic evaluation of a young man with autoimmune enterocolopathy and unexplained infections revealed evidence of immunodeficiency, including IgG subclass deficiency, impaired Ag-induced lymphocyte proliferation, reduced cytokine production by CD8(+) T lymphocytes, and decreased numbers of NK cells. Genetic evaluation identified haploinsufficiency of NFAT5, a transcription factor regulating immune cell function and cellular adaptation to hyperosmotic stress, as a possible cause of this syndrome. Inhibition or deletion of NFAT5 in normal human and murine cells recapitulated several of the immune deficits identified in the patient. These results provide evidence of a primary immunodeficiency disorder associated with organ-specific autoimmunity linked to NFAT5 deficiency. PMID:25667416

  7. Chronic enteric virus infection in two T-cell immunodeficient children.

    PubMed

    Wood, D J; David, T J; Chrystie, I L; Totterdell, B

    1988-04-01

    Enteric virus infections were studied in two children with congenital T-cell immunodeficiency. One patient (LC) with cartilage hair hypoplasia developed persistent diarrhea and malabsorption following acute gastroenteritis. Electron microscope (EM) examination of feces revealed excretion of rotavirus for more than 450 days with concurrent astrovirus infection for at least 225 days, associated with the persistent diarrhea. Prolonged infection with poliovirus type 2 following vaccination had previously been noted in this patient. The second patient (DT), with the CHARGE association and DiGeorge syndrome, had two episodes of loose stools. EM of fecal extracts demonstrated rotavirus excretion for at least 66 days following the initial episode. Virus-specific immune responses were assayed in these two patients. LC showed a poor serum neutralizing antibody response to polio vaccination, no detectable antibody response (by immune EM and ELISA) to rotavirus, and no detectable antibody response to astrovirus (by immune EM). Rotavirus specific cell mediated immunity was also not detectable. DT showed no detectable serum antibody response to rotavirus (by ELISA). Rotavirus isolates from both patients were found to be group A viruses and were further analyzed by polyacrylamide gel electrophoresis. Atypical genome profiles, with multiple additional bands between segments 3-7 of the normal rotavirus profile, were obtained throughout the course of each illness, including the earliest specimens available (day 41, LC; day 7, DT). These results indicate that chronic virus infection of the gut can occur in patients with T-cell immunodeficiency. Such chronic infection may be associated with persistent diarrhea and can cause considerable problems of management. PMID:2835434

  8. Common variable immunodeficiency and isosporiasis: first report case.

    PubMed

    Silva, Gisele Barbosa E; Fernandes, Karla Pereira; Segundo, Gesmar Rodrigues Silva

    2012-12-01

    We report a severe case of diarrhea in a 62-year-old female HIV-negative patient from whom Giardia lamblia and Isospora belli were isolated. Because unusual and opportunistic infections should be considered as criteria for further analysis of immunological status, laboratory investigations led to a diagnosis of common variable immunodeficiency (CVID). This is the first reported case of isosporiasis in a patient with CVID and illustrates the importance of being aware of a possible link, particularly in relation to primary immunodeficiency. PMID:23295886

  9. Common variable immunodeficiency disorder - An uncommon cause for bronchiectasis.

    PubMed

    Panigrahi, Manoj Kumar

    2014-10-01

    Bronchiectasis continues to be a common respiratory problem of varied etiology. Common variable immunodeficiency disorder (CVID) is an uncommon cause for bronchiectasis. However, the prevalence of bronchiectasis remains very high in patients with CVID. This remains largely an underdiagnosed entity as primary immunodeficiency is not suspected in adults as a cause of bronchiectasis and hence, serum immunoglobulin (Ig) levels are not measured routinely. In addition to bronchiectasis, patients with CVID usually present with various extrapulmonary symptoms. I report here a case of young man who presented with bronchiectasis and multisystem complains who was diagnosed as CVID. PMID:25378851

  10. Distinct Evolutionary Pressures Underlie Diversity in Simian Immunodeficiency Virus and Human Immunodeficiency Virus Lineages

    PubMed Central

    Apetrei, Cristian; Santiago, Mario L.; Li, Yingying; Gautam, Rajeev; Pandrea, Ivona; Shaw, George M.; Hahn, Beatrice H.; Letvin, Norman L.; Nabel, Gary J.

    2012-01-01

    Simian immunodeficiency virus (SIV) infection of rhesus macaques causes immune depletion and disease closely resembling human AIDS and is well recognized as the most relevant animal model for the human disease. Experimental investigations of viral pathogenesis and vaccine protection primarily involve a limited set of related viruses originating in sooty mangabeys (SIVsmm). The diversity of human immunodeficiency virus type 1 (HIV-1) has evolved in humans in about a century; in contrast, SIV isolates used in the macaque model evolved in sooty mangabeys over millennia. To investigate the possible consequences of such different evolutionary histories for selection pressures and observed diversity in SIVsmm and HIV-1, we isolated, sequenced, and analyzed 20 independent isolates of SIVsmm, including representatives of 7 distinct clades of viruses isolated from natural infection. We found SIVsmm diversity to be lower overall than HIV-1 M group diversity. Reduced positive selection (i.e., less diversifying evolution) was evident in extended regions of SIVsmm proteins, most notably in Gag p27 and Env gp120. In addition, the relative diversities of proteins in the two lineages were distinct: SIVsmm Env and Gag were much less diverse than their HIV-1 counterparts. This may be explained by lower SIV-directed immune activity in mangabeys relative to HIV-1-directed immunity in humans. These findings add an additional layer of complexity to the interpretation and, potentially, to the predictive utility of the SIV/macaque model, and they highlight the unique features of human and simian lentiviral evolution that inform studies of pathogenesis and strategies for AIDS vaccine design. PMID:23055550

  11. Neutralization tests on the SERT 2 spacecraft

    NASA Technical Reports Server (NTRS)

    Kerslake, W. R.; Domitz, S.

    1979-01-01

    Neutralization test data obtained on the SERT 2 spacecraft are presented. Tests included ion beam neutralization of a thruster by a close (normal design) neutralizer as well as by a distant (1 meter) neutralizer. Parameters affecting neutralization, such as neutralizer bias voltage, neutralizer anode voltage, local spacecraft plasma density, and solar array voltage configuration were varied and changes in plasma potentials were measured. A plasma model is presented as an approximation of observed results.

  12. Four nightmares for net neutrality

    Microsoft Academic Search

    Shane Greenstein

    2006-01-01

    What is the economic substance behind net neutrality, the populist policy debate du jour? The authors assesses the basic economics behind net neutrality. To be sure, this debate has many arcane facets. For example, a couple years ago the FCC legally exempted US broadband firms - cable modem and DSL providers - from what are known as \\

  13. The delusions of net neutrality

    Microsoft Academic Search

    Andrew Odlyzko

    2008-01-01

    Service providers argue that if net neutrality is not enforced, they will have sufficient incentives to build special high-quality channels that will take the Internet to the next level of its evolution. But what if they do get their wish, net neutrality is consigned to the dustbin, and they do build their new services, but nobody uses them? If the

  14. Net neutrality and investment incentives

    Microsoft Academic Search

    Jay Pil Choi; Byung-Cheol Kim

    2010-01-01

    This article analyzes the effects of net neutrality regulation on investment incentives for Internet service providers (ISPs) and content providers (CPs), and their implications for social welfare. Concerning the ISPs' investment incentives, we find that capacity expansion decreases the sale price of the priority right under the discriminatory regime. Thus, contrary to ISPs' claims that net neutrality regulations would have

  15. Neutral atom imaging at Mercury

    Microsoft Academic Search

    A. Mura; S. Orsini; A. Milillo; A. M. Di Lellis; E. De Angelis

    2006-01-01

    The feasibility of neutral atom detection and imaging in the Hermean environment is discussed in this study. In particular, we consider those energetic neutral atoms (ENA) whose emission is directly related to solar wind entrance into Mercury's magnetosphere. In fact, this environment is characterised by a weak magnetic field; thus, cusp regions are extremely large if compared to the Earth's

  16. ccsd00002065, Ultracold Neutral Plasmas

    E-print Network

    the electrical interaction energy between the charged particles exceeds the average kinetic energy. This reverses macroscopic particles [6], or non-neutral trapped ion plasmas [7] that are laser-cooled until they freeze, with decay rates. (A) Neutral atoms are laser cooled and trapped in a magneto- optical trap (MOT) operating

  17. Electric Trapping of Neutral Atoms

    Microsoft Academic Search

    Fujio Shimizu; Makoto Morinaga

    1992-01-01

    Two- and three-dimensional trappings of neutral atoms by an electric field are discussed. It is shown that a harmonic potential produced by the second-order Stark effect around a saddle point of the electric field intensity can be used to trap laser-cooled neutral atoms.

  18. Neutral theory and community ecology

    Microsoft Academic Search

    J. Chave

    2004-01-01

    I review the mathematical and biological aspects of Hubbell's (2001) neutral theory of species abundance for ecological communities, and clarify its historical connections with closely related approaches in population genetics. A selective overview of the empirical evidence for and against this theory is provided, with a special emphasis on tropical plant communities. The neutral theory predicts many of the basic

  19. NEUTRAL-BEAM INJECTION

    SciTech Connect

    Kunkel, W.B.

    1980-06-01

    The emphasis in the preceding chapters has been on magnetic confinement of high temperature plasmas. The question of production and heating of such plasmas has been dealt with relatively more briefly. It should not be inferred, however, that these matters must therefore be either trivial or unimportant. A review of the history reveals that in the early days all these aspects of the controlled fusion problem were considered to be on a par, and were tackled simultaneously and with equal vigor. Only the confinement problem turned out to be much more complex than initially anticipated, and richer in challenge to the plasma physicist than the questions of plasma production and heating. On the other hand, the properties of high-temperature plasmas and plasma confinement can only be studied experimentally after the problems of production and of heating to adequate temperatures are solved. It is the purpose of this and the next chapter to supplement the preceding discussions with more detail on two important subjects: neutral-beam injection and radio-frequency heating. These are the major contenders for heating in present and future tokamak and mirror fusion experiments, and even in several proposed reactors. For neutral beams we emphasize here the technology involved, which has undergone a rather remarkable development. The physics of particle and energy deposition in the plasma, and the discussion of the resulting effects on the confined plasma, have been included in previous chapters, and some experimental results are quoted there. Other heating processes of relevance to fusion are mentioned elsewhere in this book, in connection with the experiments where they are used: i.e. ohmic heating, adiabatic compression heating, and alpha-particle heating in Chapter 3 by H.P. Furth; more ohmic heating in Chapter 7, and shock-implosion heating, laser heating, and relativistic-electron beam heating in Chapter 8, both by W. E. Quinn. These methods are relatively straightforward in their physics and their technology, or in any case they are considered to be adequately covered by these other authors.

  20. Analysis of the cross-reactive anti-gp120 antibody population in human immunodeficiency virus-infected asymptomatic individuals.

    PubMed Central

    Hariharan, K; Nara, P L; Caralli, V M; Norton, F L; Haigwood, N; Kang, C Y

    1993-01-01

    This study was undertaken to analyze the specificity and neutralizing properties of cross-reactive anti-gp120 antibodies (Abs) in the sera of two human immunodeficiency virus (HIV)-infected asymptomatic individuals. Two panels of murine monoclonal anti-idiotype Abs (anti-id MAbs) were established against cross-reactive polyclonal anti-gp120 Abs purified from HIV+ sera by sequential affinity chromatography using gp120SF2- and gp120IIIB-Sepharose columns. These panels of anti-id MAbs were then used to affinity purify idiotype-positive (Id+) anti-gp120 Abs from HIV+ sera. The recovery of each of these Id+ Abs by purification indicated that several idiotypically distinct cross-reactive anti-gp120 Abs are present in sera over a wide range of concentrations. Immunological and biological studies showed that although all of the Id+ Abs were reactive against gp120SF2 and gp120IIIB, they exhibited unique epitope specificities and distinct neutralizing activities. Most of the Id+ Abs were directed against epitopes in the CD4 attachment site (CD4 site epitopes) of gp120 and exhibited a spectrum of broadly neutralizing activities. On the other hand, a minor population of Id+ Abs showed specificity for the V3 region of gp120 and exhibited limited cross-neutralizing activities. Together, these studies indicate that the CD4 site epitope-specific Abs are heterogeneous with respect to their clonality, neutralizing activity, and concentration in sera. This heterogeneity suggests that anti-gp120 Abs to the CD4 attachment site are developed in response to multiple overlapping epitopes present on the original virus isolate and/or epitopes on mutated variants which emerged over time. PMID:7678311

  1. Functional and immunologic characterization of human immunodeficiency virus type 1 envelope glycoproteins containing deletions of the major variable regions.

    PubMed Central

    Wyatt, R; Sullivan, N; Thali, M; Repke, H; Ho, D; Robinson, J; Posner, M; Sodroski, J

    1993-01-01

    Deletions of the major variable regions (V1/V2, V3, and V4) of the human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein were created to study the role of these regions in function and antigenicity. Deletion of the V4 region disrupted processing of the envelope glycoprotein precursor. In contrast, the deletion of the V1/V2 and/or V3 regions yielded processed exterior envelope glycoproteins that retained the ability to interact with the gp41 transmembrane glycoprotein and the CD4 receptor. Shedding of the gp120 exterior glycoprotein by soluble CD4 was observed for the mutant with the V3 deletion but did not occur for the V1/V2-deleted mutant. None of the deletion mutants formed syncytia or supported virus entry. Importantly, the affinity of neutralizing antibodies directed against the CD4-binding region for the multimeric envelope glycoprotein complex was increased dramatically by the removal of both the V1/V2 and V3 structures. These results indicate that, in addition to playing essential roles in the induction of membrane fusion, the major variable regions mask conserved neutralization epitopes of the HIV-1 gp120 glycoprotein from antibodies. These results explain the temporal pattern associated with generation of HIV-1-neutralizing antibodies following infection and suggest stratagems for eliciting improved immune responses to conserved gp120 epitopes. Images PMID:8331723

  2. Reticular Erythematous Mucinosis Associated with Human Immunodeficiency Virus Infection

    Microsoft Academic Search

    E. Daudén; P. F. Peñas; G. F. Buezo; J. Fraga; A. García-Diez

    1995-01-01

    We report the case of a 56-year-old woman with reticular erythematous mucinosis (REM). During her workup infection with the human immunodeficiency virus (HIV) was detected. She developed a cerebral toxoplasmosis, salmonella sp. bacteremia and oral ulcerations with the presence of type I herpes simplex virus and cytomegalovirus. The relation of REM with the deposition of mucin in AIDS patients’ bone

  3. Sino-orbital Aspergillosis in Acquired Immunodeficiency Syndrome

    Microsoft Academic Search

    Thomas E. Johnson; Roy R. Casiano; Jan W. Kronish; David T. Tse; Melissa Meldrum; Warren Chang

    1999-01-01

    Objective: To describe the clinical features, causes, im- aging characteristics, treatment, and outcome of pa- tients with the acquired immunodeficiency syndrome (AIDS) and sino-orbital aspergillosis. Design: Records of 5 patients were reviewed. Results of imaging and histopathologic examinations and clinical courses of the patients were studied. Results: There were 3 women and 2 men (mean age, 34.0 years). All had

  4. Gene Therapy for Immunodeficiency Due to Adenosine Deaminase Deficiency

    Microsoft Academic Search

    Alessandro Aiuti; Federica Cattaneo; Stefania Galimberti; Ulrike Benninghoff; Barbara Cassani; Luciano Callegaro; Samantha Scaramuzza; Grazia Andolfi; Massimiliano Mirolo; Immacolata Brigida; Antonella Tabucchi; Filippo Carlucci; Martha Eibl; Memet Aker; Shimon Slavin; Hamoud Al-Mousa; Abdulaziz Al Ghonaium; Alina Ferster; Andrea Duppenthaler; Luigi Notarangelo; Uwe Wintergerst; Rebecca H. Buckley; Marco Bregni; Sarah Marktel; Maria Grazia Valsecchi; Paolo Rossi; Fabio Ciceri; Roberto Miniero; Claudio Bordignon; Maria-Grazia Roncarolo

    2009-01-01

    Background We investigated the long-term outcome of gene therapy for severe combined immu- nodeficiency (SCID) due to the lack of adenosine deaminase (ADA), a fatal disorder of purine metabolism and immunodeficiency. Methods We infused autologous CD34+ bone marrow cells transduced with a retroviral vec- tor containing the ADA gene into 10 children with SCID due to ADA deficiency who lacked

  5. Rational Design of Drugs That Induce Human Immunodeficiency Virus Replication

    Microsoft Academic Search

    Dean H. Hamer; Sven Bocklandt; Louise McHugh; Tae-Wook Chun; Peter M. Blumberg; Dina M. Sigano; Victor E. Marquez

    2003-01-01

    Drugs that induce human immunodeficiency virus type 1 (HIV-1) replication could be used in combination with highly active antiretroviral therapy (HAART) to reduce the size of the latent reservoir that is in part responsible for viral persistence. Protein kinase C (PKC) is a logical target for such drugs because it activates HIV-1 transcription through multiple mechanisms. Here we show that

  6. Fraunhofer lines in the solar spectrum and immunodeficiency problems

    NASA Astrophysics Data System (ADS)

    Kondratyev, K. Ya.; Fedchenko, P. P.

    2004-05-01

    The importance of the presence of Fraunhofer lines in the solar spectrum for development of immunodeficiency has been demonstrated. In vitro and in vivo tests of illumination within Mg lines have proved the possibility to reduce the level of HIV/AIDS development.

  7. Promoting Early Detection of Human Immunodeficiency Virus Infection Among Adolescents

    Microsoft Academic Search

    Mary Jane Rotheram-Borus; Donna Futterman

    2000-01-01

    W hile a significant and increasing number of adolescents are infected with the hu- man immunodeficiency virus (HIV), few youth are identified as seropositive and even fewer are linked to medical care and social services. If more youth were identified, transmission to sexual partners and offspring would be reduced and individuals could benefit from treatment. Prior to initiating wide-scale early

  8. Functional domains in the feline immunodeficiency virus nucleocapsid protein

    Microsoft Academic Search

    Mariana L. Manrique; Mar??a L. Rauddi; Silvia A. González; José L. Affranchino

    2004-01-01

    Ret roviral nucleocapsid (NC) proteins are small Gag-derived products containing one or two zinc finger motifs that mediate genomic RNA packaging into virions. In this study, we addressed the role of the feline immunodeficiency virus (FIV) NC protein in the late stages of virus replication by analyzing the assembly phenotype of FIV NC mutant viruses and the RNA binding activity

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

    PubMed

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

    2010-07-01

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

  10. The German national registry for primary immunodeficiencies (PID)

    PubMed Central

    Gathmann, B; Goldacker, S; Klima, M; Belohradsky, B H; Notheis, G; Ehl, S; Ritterbusch, H; Baumann, U; Meyer-Bahlburg, A; Witte, T; Schmidt, R; Borte, M; Borte, S; Linde, R; Schubert, R; Bienemann, K; Laws, H-J; Dueckers, G; Roesler, J; Rothoeft, T; Krüger, R; Scharbatke, E C; Masjosthusmann, K; Wasmuth, J-C; Moser, O; Kaiser, P; Groß-Wieltsch, U; Classen, C F; Horneff, G; Reiser, V; Binder, N; El-Helou, S M; Klein, C; Grimbacher, B; Kindle, G

    2013-01-01

    In 2009, a federally funded clinical and research consortium (PID–NET, http://www.pid-net.org) established the first national registry for primary immunodeficiencies (PID) in Germany. The registry contains clinical and genetic information on PID patients and is set up within the framework of the existing European Database for Primary Immunodeficiencies, run by the European Society for Primary Immunodeficiencies. Following the example of other national registries, a central data entry clerk has been employed to support data entry at the participating centres. Regulations for ethics approvals have presented a major challenge for participation of individual centres and have led to a delay in data entry in some cases. Data on 630 patients, entered into the European registry between 2004 and 2009, were incorporated into the national registry. From April 2009 to March 2012, the number of contributing centres increased from seven to 21 and 738 additional patients were reported, leading to a total number of 1368 patients, of whom 1232 were alive. The age distribution of living patients differs significantly by gender, with twice as many males than females among children, but 15% more women than men in the age group 30 years and older. The diagnostic delay between onset of symptoms and diagnosis has decreased for some PID over the past 20 years, but remains particularly high at a median of 4 years in common variable immunodeficiency (CVID), the most prevalent PID. PMID:23607573

  11. 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"…

  12. Extranodal marginal zone (MALT) lymphoma in common variable immunodeficiency

    Microsoft Academic Search

    I. M. Desar; M. Keuter; J. M. M. Raemaekers; J. B. M. J. Jansen

    2006-01-01

    We describe two patients with common variable immunodeficiency (CVID) who developed extranodal marginal zone lymphoma (formerly described as mucosa-associated lymphoid tissue lymphoma or MALT lymphoma). One patient, with documented pernicious anaemia and chronic atrophic gastritis with metaplasia, developed a Helicobacter pylori-positive extranodal marginal zone lymphoma in the stomach. Three triple regimens of antibiotics were necessary to eliminate the H. pylori,

  13. Bacterial prostatitis in patients infected with the human immunodeficiency virus.

    PubMed

    Leport, C; Rousseau, F; Perronne, C; Salmon, D; Joerg, A; Vilde, J L

    1989-02-01

    Bacterial prostatitis was diagnosed in 17 of 209 human immunodeficiency virus-infected men hospitalized from October 1985 to October 1987. A history of urogenital disease was found in 13 of 17 patients. Clinical signs of prostatitis were present in 16 of 17 patients, including fever in 13, urinary symptoms in 11 and tender prostate on rectal palpation in 7. Bacteriuria was found in 14 of the 17 patients. Prostatic ultrasound examination showed an abscess in 11 of 16 patients studied. Prostatitis was diagnosed at autopsy in 1 patient. Within 6 weeks after onset of antimicrobial therapy 9 of 13 patients were cured and 4 of 13 did not respond to therapy. Among the 7 patients followed for more than 2 months after the end of antimicrobial therapy 5 had relapse. The prevalence of bacterial prostatitis among human immunodeficiency virus-infected patients increased from 3 per cent in asymptomatic human immunodeficiency virus-infected patients to 14 per cent in patients with the acquired immunodeficiency syndrome. PMID:2643725

  14. Cryptococcal prostatic abscess associated with the acquired immunodeficiency syndrome.

    PubMed

    Mamo, G J; Rivero, M A; Jacobs, S C

    1992-09-01

    A case of cryptococcal prostatic abscess in a 28-year old man with the acquired immunodeficiency syndrome is presented. This is a unique presentation of a cryptococcal prostatic infection and of a prostatic abscess. The diagnosis and management are discussed, and the literature is reviewed. PMID:1512849

  15. Inhibition of Human Immunodeficiency Virus Replication by Antisense Oligodeoxynucleotides

    Microsoft Academic Search

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

    1988-01-01

    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

  16. Molecular characterization and heterogeneity of feline immunodeficiency virus isolates

    Microsoft Academic Search

    N. Maki; T. Miyazawa; M. Fukasawa; A. Hasegawa; M. Hayami; K. Miki; T. Mikami

    1992-01-01

    Summary We have molecularly cloned the complete genomic DNA of TM2 strain of feline immunodeficiency virus (FIV) isolated in Japan and compared its nucleotide and the deduced amino acid sequence with those of previously described U.S. isolates, FIV Petaluma and FIV PPR. The infectious molecular clone of FIV TM2 is different from FIV Petaluma in host cell range; the clone

  17. Genetics Home Reference: X-linked severe combined immunodeficiency

    MedlinePLUS

    ... names Glossary definitions Reviewed May 2009 What is X-linked SCID? X-linked severe combined immunodeficiency (SCID) is an ... do not live beyond infancy. How common is X-linked SCID? X-linked SCID is the most common form ...

  18. Factors Associated With Incident Human Immunodeficiency VirusDementia

    E-print Network

    and intravenous drug use3 are associated with a greater risk of developing dementia. There has been someFactors Associated With Incident Human Immunodeficiency Virus­Dementia Yaakov Stern, PhD; Michael P; for the Dana Consortium on the Therapy of HIV­Dementia and Related Cognitive Disorders Background: Antecedents

  19. Nonexotic Neutral Gauge Bosons

    E-print Network

    Thomas Appelquist; Bogdan A. Dobrescu; Adam R. Hopper

    2003-07-17

    We study theoretical and experimental constraints on electroweak theories including a new color-singlet and electrically-neutral gauge boson. We first note that the electric charges of the observed fermions imply that any such Z' boson may be described by a gauge theory in which the Abelian gauge groups are the usual hypercharge along with another U(1) component in a kinetic-diagonal basis. Assuming that the observed quarks and leptons have generation-independent U(1) charges, and that no new fermions couple to the standard model gauge bosons, we find that their U(1) charges form a two-parameter family consistent with anomaly cancellation and viable fermion masses, provided there are at least three right-handed neutrinos. We then derive bounds on the Z' mass and couplings imposed by direct production and Z-pole measurements. For generic charge assignments and a gauge coupling of electromagnetic strength, the strongest lower bound on the Z' mass comes from Z-pole measurements, and is of order 1 TeV. If the new U(1) charges are proportional to B-L, however, there is no tree-level mixing between the Z and Z', and the best bounds come from the absence of direct production at LEPII and the Tevatron. If the U(1) gauge coupling is one or two orders of magnitude below the electromagnetic one, these bounds are satisfied for most values of the Z' mass.

  20. Is science metaphysically neutral?

    PubMed

    Fry, Iris

    2012-09-01

    This paper challenges the claim that science is metaphysically neutral upheld by contenders of the separation of peacefully co-existent science and religion and by evolutionary theists. True, naturalistic metaphysical claims can neither be refuted nor proved and are thus distinct from empirical hypotheses. However, metaphysical assumptions not only regulate the theoretical and empirical study of nature, but are increasingly supported by the growing empirical body of science. This historically evolving interaction has contributed to the development of a naturalistic worldview that renounces the necessity of a transcendent god and of purposeful design. The thesis presented here differs not only from the claims of the "separatists" and of evolutionary theists. In pointing to the metaphysical aspects of science, I also criticize the failure of some evolutionary naturalists to distinguish between empirical and metaphysical contentions. Most important, based on the examination of science suggested here, creationists' false accusation that science is only a naturalistic dogma is refuted. Finally, the difficulties involved in the position endorsed here for the public support of evolution are acknowledged, taking into account the high religious profile of the American society and the social and political context in the US and in other countries. PMID:22771725

  1. 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.

  2. Differences in HIV Type 1 Neutralization Breadth in 2 Geographically Distinct Cohorts in Africa.

    PubMed

    Bandawe, Gama P; Moore, Penny L; Werner, Lise; Gray, Elin S; Sheward, Daniel J; Madiga, Maphuti; Nofemela, Andile; Thebus, Ruwayhida; Marais, Jinny C; Maboko, Leonard; Abdool Karim, Salim S; Hoelscher, Michael; Morris, Lynn; Williamson, Carolyn

    2015-05-01

    To investigate whether distinct populations have differing human immunodeficiency virus type 1 (HIV) neutralizing antibody responses, we compared 20 women from Tanzania's HIV Superinfection Study (HISIS) cohort, who were infected multiple HIV subtypes, and 22 women from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) cohort, who were infected exclusively with HIV subtype C. By 2 years after infection, 35% of HISIS subjects developed neutralization breadth, compared with 9% of CAPRISA subjects (P = .0131). Cumulative viral loads between 3 and 12 months were higher in the HISIS group (P = .046) and strongly associated with breadth (P < .0001). While viral load was the strongest predictor, other factors may play a role, as the odds of developing breadth remained higher in HISIS even after correction for viral load. PMID:25398460

  3. Sequential injection immunoassay for human bone morphogenic protein-7 using an immunoreactor immobilized with anti-human bone morphogenic protein-7 antibody--CdSe/ZnS quantum dot conjugates.

    PubMed

    Kim, Chun-Kwang; Duong, Hong Dinh; Rhee, Jong Il

    2013-07-01

    The detection of human bone morphogenic protein-7 (BMP-7) was achieved using a sequential injection immunoassay (SIIA) system. The SIIA system is based on the binding between BMP-7 and anti-human BMP-7 (AbBMP7)-CdSe/ZnS quantum dot (QD) conjugates immobilized onto a glass disk or an optical fiber, using fluorescence detection at excitation and emission wavelengths of 470 nm and 580 nm, respectively. The AbBMP7-QD conjugates were prepared by conjugating anti-human BMP-7 antibody (AbBMP7) to hydrophilic CdSe/ZnS core/shell quantum dots (QDs). The SIIA system was fully automated using software written in the LabVIEW™ development environment. The analytical performance of the SIIA system was characterized with a number of variables such as carrier flow rate and elution buffer. Under partially optimized operating conditions, the SIIA system had a linear calibration graph at up to 10.0 ng mL(-1) BMP-7 (R(2)?0.975) and a sample frequency of two samples per hour. The SIIA system with an optical fiber immunosensor was used to detect and quantify BMP-7 in spiked real samples obtained from a biological process with recoveries in the range of 95-102%. PMID:23790295

  4. Parental Consanguinity and the Risk of Primary Immunodeficiency Disorders: Report from the Kuwait National Primary Immunodeficiency Disorders Registry

    Microsoft Academic Search

    Waleed Al-Herz; Kamal K. Naguib; Luigi D. Notarangelo; Raif S. Geha; Amal Alwadaani

    2011-01-01

    Background: It is proposed that consanguineous marriages increase the risk of primary immunodeficiency disorders (PID). The aim of this study is to review the frequency and pattern of parental consanguinity among PID patients and to determine its effects on the distribution of different PID, the patients’ performance status and the risk of death. Method: The data was obtained from the

  5. Relationship of the human immunodeficiency virus type 1 gp120 third variable loop to a component of the CD4 binding site in the fourth conserved region.

    PubMed Central

    Wyatt, R; Thali, M; Tilley, S; Pinter, A; Posner, M; Ho, D; Robinson, J; Sodroski, J

    1992-01-01

    Neutralizing antibodies that recognize the human immunodeficiency virus gp120 exterior envelope glycoprotein and are directed against either the third variable (V3) loop or conserved, discontinuous epitopes overlapping the CD4 binding region have been described. Here we report several observations that suggest a structural relationship between the V3 loop and amino acids in the fourth conserved (C4) gp120 region that constitute part of the CD4 binding site and the conserved neutralization epitopes. Treatment of the gp120 glycoprotein with ionic detergents resulted in a V3 loop-dependent masking of both linear C4 epitopes and discontinuous neutralization epitopes overlapping the CD4 binding site. Increased recognition of the native gp120 glycoprotein by an anti-V3 loop monoclonal antibody, 9284, resulted from from single amino acid changes either in the base of the V3 loop or in the gp120 C4 region. These amino acid changes also resulted in increased exposure of conserved epitopes overlapping the CD4 binding region. The replication-competent subset of these mutants exhibited increased sensitivity to neutralization by antibody 9284 and anti-CD4 binding site antibodies. The implied relationship of the V3 loop, which mediates post-receptor binding steps in virus entry, and components of the CD4 binding region may be important for the interaction of these functional gp120 domains and for the observed cooperativity of neutralizing antibodies directed against these regions. Images PMID:1279195

  6. Generation of infectious feline immunodeficiency virus (FIV) encoding FIV/human immunodeficiency virus chimeric protease.

    PubMed

    Lin, Ying-Chuan; Torbett, Bruce E; Elder, John H

    2010-07-01

    Feline immunodeficiency virus (FIV) and human immunodeficiency virus type 1 (HIV-1) proteases (PRs) share only 23% amino acid identity and exhibit distinct specificities yet have very similar 3-dimensional structures. Chimeric PRs in which HIV residues were substituted in structurally equivalent positions in FIV PR were prepared in order to study the molecular basis of PR specificity. Previous in vitro analyses showed that such substitutions dramatically altered the inhibitor specificity of mutant PRs but changed the rate and specificity of Gag cleavage so that chimeric FIVs were not infectious. Chimeric PRs encoding combinations of the I37V, N55M, M56I, V59I, L97T, I98P, Q99V, and P100N mutations were cloned into FIV Gag-Pol, and those constructs that best approximated the temporal cleavage pattern generated by wild-type FIV PR, while maintaining HIV-like inhibitor specificity, were selected. Two mutations, M56I and L97T, were intolerant to change and caused inefficient cleavage at NC-p2. However, a mutant PR with six substitutions (I37V, N55M, V59I, I98P, Q99V, and P100N) was selected and placed in the context of full-length FIV-34TF10. This virus, termed YCL6, had low-level infectivity ex vivo, and after passage, progeny that exhibited a higher growth rate emerged. The residue at the position of one of the six mutations, I98P, further mutated on passage to either P98H or P98S. Both PRs were sensitive to the HIV-1 PR inhibitors lopinavir (LPV) and darunavir (DRV), as well as to the broad-based inhibitor TL-3, with 50% inhibitory concentrations (IC(50)) of 30 to 40 nM, consistent with ex vivo results obtained using mutant FIVs. The chimeras offer an infectivity system with which to screen compounds for potential as broad-based PR inhibitors, define structural parameters that dictate specificity, and investigate pathways for drug resistance development. PMID:20410281

  7. 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.

  8. Trustworthiness as a Limitation on Network Neutrality

    E-print Network

    Schneider, Fred B.

    ............................................................................ D. Trustworthiness and Wireless Net Neutrality.................. IV. KEEPING TRUSTWORTHINESS591 Trustworthiness as a Limitation on Network Neutrality Aaron J. Burstein* Fred B. Schneider** I TRUSTWORTHINESS THROUGH THE NETWORK NEUTRALITY DEBATE

  9. Diagnostics of fast neutral beams

    NASA Astrophysics Data System (ADS)

    Ranjan, Alok

    As device dimensions continue to shrink, charging damage during reactive ion etching (RIE) has become a serious concern. Fast neutral beams with energies of tens to hundreds of eV may be useful for mitigating charging damage. For neutral beam processing to be viable, however, the beam energy, flux and directionality must be comparable to those in RIE. Characterization of neutral beams in terms of flux and energy distributions is therefore of critical importance. In the neutral beam source implemented in this study, positive ions generated in an inductively coupled argon plasma were extracted through a metal (or silicon) neutralization grid with high aspect ratio holes (or trenches). Ions suffering grazing angle collisions with the inside surface of the grid holes turned into fast neutrals. The fast neutral energy distribution (NED) was measured by ionizing a small fraction of the fast neutrals using an electron beam, and detecting the resulting ions with an electrostatic parallel-plate ion energy analyzer. Calorimetry was employed to deduce the flux of fast neutrals and residual ions. The neutral energy distribution shifted to lower energies compared to the corresponding residual ion energy distribution. The neutralization efficiency increased with power, decreased with the imposed plasma potential (controlled by an electrode). The residual ion flux decreased with increasing hole diameter and hole aspect ratio. The fast neutral flux first increased and then decreased as the hole diameter was increased. These results were explained based on plasma molding inside the grid holes. The effect of surface roughness of the grid walls on the energy distribution and flux of fast neutrals and residual ions was also studied. With a nearly atomically smooth Si grid, a small fraction of fast neutrals was observed at energies nearly equal to the maximum ion energy. For the metal grids, with rougher surfaces, the highest energy neutrals were well below the maximum ion energy. These observations were explained in terms of the type of scattering (specular vs. non-specular) that occurs when ions are converted into fast neutrals. A new diagnostic based on fast atom-atom ionization was developed to measure the energy distribution of a fast neutral beam. The ionized species (produced by fast atom-atom ionization in chamber of controlled background pressure) current was measured as a function of energy with a gridded energy analyzer. A pulsed-plasma technique was implemented to achieve a nearly monoenergetic ion beam. Ion energy was controlled by a DC bias, applied on an electrode in contact with the plasma, during part of the afterglow period. The energy spread was 3.3 eV (FWHM) for a peak residual ion beam energy of 101.5 eV. For a grid with smooth surfaces, NED peak at 86 eV with an energy spread of 14 eV. Energy shifts and broadening of NED were explained by specular reflection and distribution of angle of incidence of ions at the grid hole surfaces.

  10. Human immunodeficiency virus type-1 reverse transcriptase and ribonuclease H as substrates of the viral protease.

    PubMed Central

    Tomasselli, A. G.; Sarcich, J. L.; Barrett, L. J.; Reardon, I. M.; Howe, W. J.; Evans, D. B.; Sharma, S. K.; Heinrikson, R. L.

    1993-01-01

    A study has been made of the susceptibility of recombinant constructs of reverse transcriptase (RT) and ribonuclease H (RNase H) from human immunodeficiency virus type 1 (HIV-1) to digestion by the HIV-1 protease. At neutral pH, the protease attacks a single peptide bond, Phe440-Tyr441, in one of the protomers of the folded, active RT/RNase H (p66/p66) homodimer to give a stable, active heterodimer (p66/p51) that is resistant to further hydrolysis (Chattopadhyay, D., et al., 1992, J. Biol. Chem. 267, 14227-14232). The COOH-terminal p15 fragment released in the process, however, is rapidly degraded by the protease by cleavage at Tyr483-Leu484 and Tyr532-Leu533. In marked contrast to this p15 segment, both p66/p51 and a folded RNase H construct are stable to breakdown by the protease at neutral pH. It is only at pH values around 4 that these latter proteins appear to unfold and, under these conditions, the heterodimer undergoes extensive proteolysis. RNase H is also hydrolyzed at low pH, but cleavage takes place primarily at Gly436-Ala437 and at Phe440-Tyr441, and only much more slowly at residues 483, 494, and 532. This observation can be reconciled by inspection of crystallographic models of RNase H, which show that residues 483, 494, and 532 are relatively inaccessible in comparison to Gly436 and Phe440. Our results fit a model in which the p66/p66 homodimer exists in a conformation that mirrors that of the heterodimer, but with a p15 segment on one of the protomers that is structurally disordered to the extent that all of its potential HIV protease cleavage sites are accessible for hydrolysis. PMID:7507754

  11. A neutral lithium beam source

    Microsoft Academic Search

    Xiaodong Zhang; Zhengmin Wang; Liqun Hu

    1994-01-01

    A low energy neutral lithium beam source with energy about 6 keV and a neutral beam equivalent current of 20 ?A\\/cm2 has been developed in ASIPP in order to measure the density gradient and the fluctuations in the edge plasma of the HT-6M tokamak. In the source, lithium ions are extracted from a solid emitter (?-eucryptite), focused in a two-tube

  12. Influence of random genetic drift on human immunodeficiency virus type 1 env evolution during chronic infection.

    PubMed Central

    Shriner, Daniel; Shankarappa, Raj; Jensen, Mark A; Nickle, David C; Mittler, John E; Margolick, Joseph B; Mullins, James I

    2004-01-01

    Human immunodeficiency virus type 1 (HIV-1) has high replication and mutation rates that generate large census populations and high levels of genetic variation. We examined the roles of natural selection, population growth, random genetic drift, and recombination in shaping the variation in 1509 C2-V5 env sequences derived from nine men with chronic HIV-1 infection. These sequences were obtained from clinical visits that reflect the first 6-13.7 years of infection. Pairwise comparisons of nonsynonymous and synonymous distances, Tajima's D test, Fu and Li's D* test, and a test of recurrent mutation revealed evidence for episodes of nonneutral evolution in a total of 22 out of 145 blood samples, representing six of the nine individuals. Using three coalescent-based maximum-likelihood estimators, we found viral effective population sizes in all nine individuals to be approximately 10(3). We also show that a previous estimate of the effective population size of approximately 10(5) based on rare haplotype frequencies decreases to approximately 10(3) upon correcting a biased sampling procedure. We conclude that the genetic variation in these data sets can be explained by a predominance of random genetic drift of neutral mutations with brief episodes of natural selection that were frequently masked by recombination. PMID:15082537

  13. Serological responses in chimpanzees inoculated with human immunodeficiency virus glycoprotein (gp120) subunit vaccine

    SciTech Connect

    Arthur, L.O.; Pyle, S.W.; Nara, P.L.; Bess, J.W. Jr.; Gonda, M.A.; Kelliher, J.C.; Gilden, R.V.; Robey, W.G.; Bolognesi, D.P.; Gallo, R.C.

    1987-12-01

    The major envelope glycoprotein of a human immunodeficiency virus (HIV) has been purified and was utilized as a prototype vaccine in chimpanzees. The 120,000-dalton glycoprotein (gp120) was purified from membranes of human T-lymphotropic virus (HTLV)-IIIB-infected cells and the final preparation contained low levels to no detectable HTLV-IIIB core antigen (p24) and low levels of endotoxin. Chimpanzees inoculated with gp120 responded by developing antibodies that precipitated radiolabeled gp120 and neutralized in vitro infection of HTLV-IIIB. Antibodies to HTLV-IIIB p24 were not detected in the gp120-immunized chimpanzees. Peripheral blood leukocytes from the vaccinated animals were examined for T4/sup +/ and T8/sup +/ cells, and no decrease in the T4/T8 ratio was found, indicating that immunization with a ligand (gp120) that binds to T4 has not detectable adverse effect on the population of T4/sup +/ cells. The only current animal model that can be reproducibly infected with HIV is the chimpanzee. Immunization of chimpanzees with HIV proteins will provide an experimental system for testing the effectiveness of prototype vaccines for preventing HIV infection in vivo.

  14. Mucosal model of immunization against human immunodeficiency virus type 1 with a chimeric influenza virus.

    PubMed Central

    Muster, T; Ferko, B; Klima, A; Purtscher, M; Trkola, A; Schulz, P; Grassauer, A; Engelhardt, O G; García-Sástre, A; Palese, P

    1995-01-01

    Previously, we constructed a chimeric influenza virus that expresses the highly conserved amino acid sequence ELDKWA of gp41 of human immunodeficiency virus type 1 (HIV-1). Antisera elicited in mice by infection with this chimeric virus showed neutralizing activity against distantly related HIV-1 isolates (T. Muster, R. Guinea, A. Trkola, M. Purtscher, A. Klima, F. Steindl, P. Palese, and H. Katinger, J. Virol. 68:4031-4034, 1994). In the present study, we demonstrated that intranasal immunizations with this chimeric virus are also able to induce a humoral immune response at the mucosal level. The immunized mice had ELDKWA-specific immunoglobulins A in respiratory, intestinal, and vaginal secretions. Sustained levels of these secretory immunoglobulins A were detectable for more than 1 year after immunization. The results show that influenza virus can be used to efficiently induce secretory antibodies against antigens from foreign pathogens. Since long-lasting mucosal immunity in the genital and intestinal tracts might be essential for protective immunity against HIV-1, influenza virus appears to be a promising vector for HIV-1-derived immunogens. PMID:7474077

  15. Prevention of infection by a granulocyte-macrophage colony-stimulating factor co-expressing DNA/modified vaccinia Ankara simian immunodeficiency virus vaccine.

    PubMed

    Lai, Lilin; Kwa, Suefen; Kozlowski, Pamela A; Montefiori, David C; Ferrari, Guido; Johnson, Welkin E; Hirsch, Vanessa; Villinger, Francois; Chennareddi, Lakshmi; Earl, Patricia L; Moss, Bernard; Amara, Rama Rao; Robinson, Harriet L

    2011-07-01

    A simian immunodeficiency virus (SIV) vaccine coexpressing granulocyte-macrophage colony stimulating factor (GM-CSF) prevented infection in 71% of macaques that received 12 rectal challenges. The SIVsmE660 challenge had the tropism of incident human immunodeficiency virus (HIV) infections and a similar genetic distance from the SIV239 vaccine as intraclade HIV isolates. The heterologous prime-boost vaccine regimen used recombinant DNA for priming and recombinant modified vaccinia Ankara for boosting. Co-expression of GM-CSF in the DNA prime enhanced the avidity of elicited immunoglobulin G for SIV envelope glycoproteins, the titers of neutralizing antibody for easy-to-neutralize SIV isolates, and antibody-dependent cellular cytotoxicity. Impressively, the co-expressed GM-CSF increased vaccine-induced prevention of infection from 25% in the non-GM-CSF co-expressing vaccine group to 71% in the GM-CSF co-expressing vaccine group. The prevention of infection showed a strong correlation with the avidity of the elicited Env-specific antibody for the Env of the SIVsmE660 challenge virus (r = 0.9; P < .0001). PMID:21628671

  16. Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals

    SciTech Connect

    Sutjipto, S.; Pedersen, N.C.; Miller, C.J.; Gardner, M.B.; Hanson, C.V.; Gettie, A.; Jennings, M.; Higgins, J.; Marx, P.A. (Univ. of California, Davis (USA))

    1990-05-01

    Eight rhesus macaques were immunized four times over a period of 8 months with a psoralen-UV-light-inactivated whole simian immunodeficiency virus vaccine adjuvanted with threonyl muramyl dipeptide. Eight unvaccinated control animals received adjuvant alone. Only the vaccinated animals made antibodies before challenge exposure to the viral core and envelope as determined by Western blotting (immunoblotting) and virus-neutralizing antibodies. Ten days after the final immunization, one-half of the vaccinated and nonvaccinated monkeys were challenged exposed intravenously (i.v.) and one-half were challenge exposed via the genital mucosa with virulent simian immunodeficiency virus. All of the nonvaccinated control monkeys became persistently infected. In spite of preexisting neutralizing antibodies and an anamnestic antibody response, all of the immunized monkeys also became persistently infected. However, there was evidence that the clinical course in immunized i.v. infected animals was delayed. All four mock-vaccinated i.v. challenge-exposed animals died with disease from 3 to 9 months postchallenge. In contrast, only one of four vaccinated i.v. challenge-exposed monkeys had died by 11 months postchallenge.

  17. Transfer of rheumatoid arthritis into severe combined immunodeficient mice. The pathogenetic implications of T cell populations oligoclonally expanding in the rheumatoid joints.

    PubMed Central

    Mima, T; Saeki, Y; Ohshima, S; Nishimoto, N; Matsushita, M; Shimizu, M; Kobayashi, Y; Nomura, T; Kishimoto, T

    1995-01-01

    To investigate the pathogenicity of T cells infiltrating in the rheumatoid joints, mononuclear cells (MNC), predominantly T cells, isolated from either synovial fluid or synovial tissues of the patients with RA were transferred into severe combined immunodeficient (SCID) mice by intraarticular injections. According to our observations in this experimental system, patients with RA could be classified into at least two groups. In one group of patients, the infiltrating MNC induced synovial hyperplasia in the recipient SCID mice (the positive group). Whereas, in the other group no synovial hyperplasia was observed (the negative group). The induction of synovial hyperplasia observed in the positive group was prevented by an anti-human CD3 antibody (OKT3), indicating T cell mediation. Analysis of T cell receptor (TCR) V beta usage by reverse transcriptase polymerase chain reaction in the infiltrating MNC transferred into SCID mice revealed a marked skew towards the preferential use of certain V beta genes, which was not seen in the peripheral blood MNC, in only the positive group. The patterns of TCR/V beta skew were not uniform among the patients. The analysis of the PCR-amplified genes of such skewed TCR/ V beta by single strand conformational polymorphism showed distinct bands, indicating that the T cell populations expanding in rheumatoid joints of the positive group were oligoclonal. Furthermore, the enrichment of the T cell populations expressing such skewed TCR/V beta by in vitro stimulation of peripheral blood MNC of the patients with the relevant superantigen enabled the induction of synovial hyperplasia in the SCID mice. These results suggest that the pathogenic T cells could be activated locally in rheumatoid joints by certain antigens in some, but not in all patients with RA. Images PMID:7560066

  18. Romiplostim as early treatment of immune thrombocytopenia with severe immunodeficiency

    PubMed Central

    Palandri, Francesca; Polverelli, Nicola; Lifrieri, Francesca; Catani, Lucia; Giannini, Maria Benedetta; Baccarani, Michele; Vianelli, Nicola

    2012-01-01

    Immunosuppressive agents are the standard therapeutic approach for immune thrombocy-topenia (ITP). Their prolonged use may increase the risk of infectious complications, particularly when the patient is already at higher infectious risk. In this setting, the use of drugs with a mechanism of action alternative to immunosuppression, like thrombopoietin receptor agonists (TRAs), may find particular indication. We report the unique case of a patient with severe immunodeficiency and ITP, who experienced a serious infectious complication while on steroids treatment, and who was successfully treated with Romiplostim second-line. The present experience supports the effectiveness and safety of TRAs as early treatment of ITP patients with drug-induced immunodeficiency or with active infections. PMID:22826792

  19. Progress and prospects: gene therapy for inherited immunodeficiencies.

    PubMed

    Qasim, W; Gaspar, H B; Thrasher, A J

    2009-11-01

    Haematopoietic stem cell transplantation (HSCT) is now widely used to treat primary immunodeficiencies (PID). For patients with specific disorders (severe combined immunodeficiency (SCID)-X1, adenosine deaminase deficiency (ADA)-SCID, X-chronic granulomatous disease (CGD) and Wiskott-Aldrich Syndrome (WAS)) who lack a suitable human leukocyte antigen (HLA)-matched donor, gene therapy has offered an important alternative treatment option. The success of gene therapy can be attributed, in part, to the selective advantage offered to gene-corrected cells, the avoidance of graft-versus-host disease and to the use of pre-conditioning in patients with chemotherapy to facilitate engraftment of corrected cells. Adverse events have been encountered and this has led to detailed characterization of retroviral vector integration profiles. A new generation of self-inactivating retroviral and lentiviral vectors have been designed to address these safety concerns, and are at an advanced stage of preparation for the next phase of clinical testing. PMID:19776764

  20. The neuropathogenesis of feline immunodeficiency virus infection: Barriers to overcome

    PubMed Central

    Fletcher, Nicola F.; Meeker, Rick B.; Hudson, Lola C.; Callanan, John J.

    2010-01-01

    Feline immunodeficiency virus (FIV), like human immunodeficiency virus (HIV)-1, is a neurotropic lentivirus, and both natural and experimental infections are associated with neuropathology. FIV enters the brain early following experimental infection, most likely via the blood-brain and blood-cerebrospinal fluid barriers. The exact mechanism of entry, and the factors that influence this entry, are not fully understood. As FIV is a recognised model of HIV-1 infection, understanding such mechanisms is important, particularly as HIV enters the brain early in infection. Furthermore, the development of strategies to combat this central nervous system (CNS) infection requires an understanding of the interactions between the virus and the CNS. In this review the results of both in vitro and in vivo FIV studies are assessed in an attempt to elucidate the mechanisms of viral entry into the brain. PMID:20418131

  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. Acquired immunodeficiency syndrome associated with blood-product transfusions

    SciTech Connect

    Jett, J.R.; Kuritsky, J.N.; Katzmann, J.A.; Homburger, H.A.

    1983-11-01

    A 53-year-old white man had fever, malaise, and dyspnea on exertion. His chest roentgenogram was normal, but pulmonary function tests showed impaired diffusion capacity and a gallium scan showed marked uptake in the lungs. Results of an open-lung biopsy documented Pneumocystis carinii pneumonia. Immunologic test results were consistent with the acquired immunodeficiency syndrome. The patient denied having homosexual contact or using intravenous drugs. Twenty-nine months before the diagnosis of pneumocystis pneumonia was made, the patient had had 16 transfusions of whole blood, platelets, and fresh-frozen plasma during coronary artery bypass surgery at another medical center. This patient is not a member of any currently recognized high-risk group and is believed to have contracted the acquired immunodeficiency syndrome from blood and blood-product transfusions.

  3. Romiplostim as early treatment of immune thrombocytopenia with severe immunodeficiency.

    PubMed

    Palandri, Francesca; Polverelli, Nicola; Lifrieri, Francesca; Catani, Lucia; Giannini, Maria Benedetta; Baccarani, Michele; Vianelli, Nicola

    2012-05-10

    Immunosuppressive agents are the standard therapeutic approach for immune thrombocy-topenia (ITP). Their prolonged use may increase the risk of infectious complications, particularly when the patient is already at higher infectious risk. In this setting, the use of drugs with a mechanism of action alternative to immunosuppression, like thrombopoietin receptor agonists (TRAs), may find particular indication. We report the unique case of a patient with severe immunodeficiency and ITP, who experienced a serious infectious complication while on steroids treatment, and who was successfully treated with Romiplostim second-line. The present experience supports the effectiveness and safety of TRAs as early treatment of ITP patients with drug-induced immunodeficiency or with active infections. PMID:22826792

  4. Clinical aspects of feline immunodeficiency and feline leukemia virus infection.

    PubMed

    Hartmann, Katrin

    2011-10-15

    Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with a global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FIV can cause an acquired immunodeficiency syndrome that increases the risk of developing opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia) and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less important as a deadly infectious agent as in the last 20 years prevalence has been decreasing in most countries. PMID:21807418

  5. Newborn screening for primary immunodeficiencies: beyond SCID and XLA.

    PubMed

    Borte, Stephan; Wang, Ning; Oskarsdóttir, Sólveig; von Döbeln, Ulrika; Hammarström, Lennart

    2011-12-01

    Primary immunodeficiencies (PID) encompass more than 250 disease entities, including phagocytic disorders, complement deficiencies, T cell defects, and antibody deficiencies. While differing in clinical severity, early diagnosis and treatment is of considerable importance for all forms of PID to prevent organ damage and life-threatening infections. During the past few years, neonatal screening assays have been developed to detect diseases hallmarked by the absence of T or B lymphocytes, classically seen in severe combined immunodeficiencies (SCID) and X-linked agammaglobulinemia (XLA). As described in this review, a reduction or lack of T and B cells in newborns is also frequently found in several other forms of PID, requiring supplemental investigation and involving the development of additional technical platforms in order to help classify abnormal screening results. PMID:22236436

  6. Inhibition of human immunodeficiency virus type-1 integrase by curcumin

    Microsoft Academic Search

    Abhijit Mazumder; Krishnamachari Raghavan; John Weinstein; Kurt W. Kohn; Yves Pommier

    1995-01-01

    Curcumin (diferuloylmethane) is the yellow pigment in turmeric (Curcuma longa L.) that is widely used as a spice, food coloring (curry) and preservative. Curcumin exhibits a variety of pharmacological effects including antitumor, anti-inflammatory, and anti-infectious activities and is currently in clinical trials for AIDS patients. The effects of curcumin have been determined on purified human immunodeficiency virus type 1 (HIV-1)

  7. Urinary Tract Infections in Male Veterans With Human Immunodeficiency Virus

    PubMed Central

    Eccles-Radtke, Caitlin; Rector, Thomas S.; Cutting, Andrea; Drekonja, Dimitri M.

    2014-01-01

    Treatment duration for men with urinary tract infection (UTI) and human immunodeficiency virus (HIV) infection is unknown. Fiscal year 2009 Veterans Affairs administrative data were used to compare men with HIV and UTI with non-HIV men with UTI. Antimicrobial selection and duration were similar. Shorter treatment (?7 days) did not affect recurrence, suggesting that treatment beyond 7 days may be unnecessary. PMID:25734168

  8. Neuropathogenesis of Simian Immunodeficiency Virus infection in macaque monkeys

    Microsoft Academic Search

    Vito G Sasseville; Andrew A Lackner

    1997-01-01

    Patients infected with human immunodeficiency virus (HIV) develop immunologic dysfunction and multiorgan inflammatory diseases directly associated with HIV-1 infection. Of these inflammatory diseases, the most devastating to the HIV-infected patient is involvement of the central nervous system (CNS). The pathogenesis of the clinical syndrome observed in these patients, termed HIV-associated dementia, remains poorly understood. However, as most of the detectable

  9. The acquired immunodeficiency syndrome (AIDS): Memorandum from a WHO Meeting*

    PubMed Central

    1985-01-01

    An International Conference on Acquired Immunodeficiency Syndrome (AIDS), sponsored by the United States Department of Health and Human Services and the World Health Organization, was held in Atlanta on 15-17 April 1985. More than 3000 participants from 50 countries attended. This conference was followed by a meeting organized by WHO on 18-19 April where the participants reviewed the information presented at the conference and assessed its international health implications, which are described in this Memorandum. PMID:3878739

  10. Gene Therapy of X-Linked Severe Combined Immunodeficiency

    Microsoft Academic Search

    Salima Hacein-Bey-Abina; Alain Fischer; Marina Cavazzana-Calvoa

    2002-01-01

    Severe combined immunodeficiency (SCID) conditions appear to be the best possible candidates for a gene therapy approach.\\u000a Transgene expression by lymphocyte precursors should confer to these cells a selective growth advantage that gives rise to\\u000a long-lived T-lymphocytes. This rationale was used as a basis for a clinical trial of the SCID-X1 disorder caused by common\\u000a ? (?c) gene mutations. This

  11. Gastrointestinal complications of congenital immunodeficiency states. The surgeon's role.

    PubMed Central

    Mulholland, M W; Delaney, J P; Foker, J E; Leonard, A S; Simmons, R L

    1983-01-01

    Ninety-one congenitally immunodeficient patients treated from 1972 to 1981 were reviewed to assess the incidence and nature of gastrointestinal complications. Thirty-three of these patients (36%) developed 59 complications. Patients with immunodeficiencies characterized by neutrophil dysfunction--chronic granulomatous disease (20 patients) and cyclic neutropenia (eight patients)--developed 22 surgical infections, 22 of which required operation. In patients with neutrophil defects, postoperative morbidity was frequent and severe. Gastrointestinal symptoms were common in patients with isolated defects of B or T lymphocytes. Ten of forty-one patients with congenital hypogammaglobulinemia developed gastrointestinal complications, as did one of four patients with DiGeorge Syndrome, and the single patient with secretory IgA deficiency. However, operation was not required for these patients with isolated disorders of lymphocyte function. Patients with combined B and T cell disorders developed gastrointestinal disease, requiring operative therapy at intermediate rates. Gastrointestinal symptoms developed in four of nine patients with severe combined immunodeficiency and three of eight with Wiskott-Aldrich syndrome. Operative therapy was required in two of these seven symptomatic patients. PMID:6605728

  12. [Infection due to Mycobacterium bovis in common variable immunodeficiency].

    PubMed

    Herrera-Sánchez, Diana Andrea; Castilla-Rodríguez, Jaisel Luz; Castrejón-Vázquez, María Isabel; Vargas-Camaño, María Eugenia; Medina-Torres, Edgar Alejandro; Blancas-Galicia, Lizbeth; Espinosa-Padilla, Sara Elva

    2015-01-01

    Common variable immunodeficiency (CVID) is an heterogeneous group of disorders characterized by impaired antibody production. It shows a wide spectrum of manifestations including severe and recurrent respiratory infections (Streptococcus pneumoniae, Haemophilus) and gastrointestinal (Campylobacter jejuni, rotavirus and Giardia lamblia). Viral infections caused by herpes zoster, cytomegalovirus (CMV) and hepatitis C are rare. The opportunistic agents such as CMV, Pneumocystis jirovecii, cryptococcus and atypical mycobacteria have been reported as isolated cases. This paper reports the case of a 38-year-old female patient, who began six years before with weight loss of 7 kg in six months, fatigue, weakness, sweating, fever and abdominal pain. Furthermore, patient had intestinal obstruction and abdominal CT showed mesenteric lymph growth. The mesenteric lymph node biopsy revealed positives Mycobacterium PCR, Ziehl-Neelsen staining and culture for M. bovis. In the laparotomy postoperative period was complicated with nosocomial pneumonia, requiring mechanical ventilation and tracheostomy. Two years later, she developed right renal abscess that required surgical drainage, once again with a positive culture for Mycobacterium bovis. She was referred to highly specialized hospital and we documented panhypogammaglobulinemia and lymphopenia. Secondary causes of hypogammaglobulinemia were ruled out and common variable immunodeficiency (CVID) was confirmed, we started IVIG replacement. Four years later she developed mixed cellularity Hodgkin's lymphoma. Until today she continues with IVIG and chemotherapy. This report of a patient with CVID and Mycobacterium bovis infection, a unusual association, shows the cellular immunity susceptibility in this immunodeficiency, additional to the humoral defect. PMID:25758115

  13. Common variable immunodeficiency and autoimmunity--an inconvenient truth.

    PubMed

    Xiao, Xiao; Miao, Qi; Chang, Christopher; Gershwin, M Eric; Ma, Xiong

    2014-08-01

    Coexisting morbidities in CVID include bronchiectasis, autoimmunity and malignancies. The incidence of autoimmune disease in CVID patients may approach 20% of cases. The most common autoimmune disease found in CVID patients is autoimmune cytopenia, but rheumatoid arthritis, lupus, and now primary biliary cirrhosis have also been reported. The coexistence of immunodeficiency and autoimmunity appears paradoxical, since one represents a hypoimmune state and the other a hyperimmune state. However, this paradox may not actually be all that implausible due to the complex nature of immune cells, signaling pathways and their interactions. The cellular alterations in combined variable immunodeficiency include a range of T and B cell abnormalities. Selective immune derangements found in CVID include a downregulation of regulatory T cells (Treg cells), accelerated T cell apoptosis, abnormal cytokine production secondary to cytokine gene polymorphisms and increased autoreactive B cell production. The impact of these abnormalities on T and B cell interaction may not only explain the immunodeficiency but also the development of autoimmunity in select groups of patients with CVID. The variability in the clinical manifestations of CVID as a result of this immune interaction suggests that CVID is not one disease but many. This is important because it follows that the treatment of CVID may not always be the same, but may need to be directed specifically towards each individual patient. PMID:24747700

  14. Soluble CD4 enhances simian immunodeficiency virus SIVagm infection.

    PubMed Central

    Werner, A; Winskowsky, G; Kurth, R

    1990-01-01

    The CD4 molecule is expressed on T-helper cells and serves as the cellular receptor for the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and for the simian immunodeficiency viruses SIVmac and SIVagm. HIV-1, HIV-2, and SIVmac infectivity can be blocked by monoclonal antibodies (MAbs) directed against the CD4 molecule and by soluble CD4 proteins (sCD4). In the present study, we demonstrated not only lack of inhibition, but 10- to 100-fold sCD4-dependent enhancement of SIVagm infectivity of human T-cell lymphoma lines, although SIVagm infection was blocked by MAbs OKT4a and Leu3a. SIVagm enhancement with sCD4 was suppressed by MAbs OKT4a and Leu3a to levels observed without addition of sCD4. The infectivity of all four tested SIVagm variants was enhanced by sCD4 on all tested lymphoma cell lines. These results suggest a second step (second or secondary receptor) required for enhancing virus entry into the cell and may have serious implications for approaches to the treatment of acquired immunodeficiency syndrome on the basis of modified sCD4 molecules. PMID:1700834

  15. Health Related Quality of Life in Common Variable Immunodeficiency

    PubMed Central

    Quinti, Isabella; Di Pietro, Cristina; Martini, Helene; Pesce, Anna Maria; Lombardi, Francesca; Baumghartner, Maddalena; Colantuono, Stefania; Milito, Cinzia

    2012-01-01

    Purpose To quantify the health related quality of life in primary immunodeficiency patients. Materials and Methods We used generic health status and general psychological health questionnaires to determine the range of issues that needed to be considered in examining the burden of common variable immunodeficiency (CVID). Results The health status of patients with CVID was lower than that observed in normal subjects. Overall, Role-Physical and General Health scales correlated with a poorer clinical status. Surprisingly, the duration of disease did not influence health status. Being female, older, General Health Questionnaire-positive and alexithymic proved to be major risk factors associated with a poor health status. Patients with chronic lung disease and chronic diarrhea had the lowest values on the Medical Outcome Study, Short Form SF-36 (SF-36) scales. Disease severity perception was associated with the General Health Questionnaire and alexithymia status. Limitations in daily activities as a result of lower physical health were the major problems facing common variable immunodeficiency patients. Conclusion Our data underlined the importance of conducting a periodical health related quality of life assessment on patients with primary antibody deficiencies and, moreover, stressed the necessity of providing psychological support to at risk patients. PMID:22477006

  16. Ralstonia pickettii-Induced Ataxia in Immunodeficient Mice

    PubMed Central

    Berard, Marion; Medaille, Christine; Simon, Meredith; Serre, Stéphanie; Pritchett-Corning, Kathleen; Dangles-Marie, Virginie

    2009-01-01

    We report here the characterization of an asymmetric ataxia syndrome (head tilt and circling, with death in the most severe cases) demonstrated by profoundly immunodeficient mice housed at the Institut Curie SPF facility. The immune system of the affected mice had been genetically modified so that they were deficient in both B and T cells. Extensive bacteriologic, parasitic, serologic, and histopathologic analysis of the affected animals and their healthy controls led us to identify Ralstonia pickettii as the causative agent of the ataxic syndrome. The outbreak was managed through a test-and-cull process. Even though they also carried Ralstonia pickettii, immunocompetent mice that were kept in the same facility, did not show any of the signs that were expressed by their immunodeficient counterparts. This case highlights the difficulty of maintaining immunocompetent and immunodeficient mice in the same microbiologic unit and the importance of enlarging the spectrum of health monitoring to opportunistic agents when investigating clinical cases in populations of immunocompromised rodents. PMID:19389312

  17. Neutralization of porcine endogenous retrovirus by antibodies against the membrane-proximal external region of the transmembrane envelope protein.

    PubMed

    Waechter, Alexander; Eschricht, Magdalena; Denner, Joachim

    2013-03-01

    Immunization of different species including goats, rats, hamsters and guinea pigs with the recombinant ectodomain of the transmembrane envelope (TM) protein p15E of porcine endogenous retrovirus (PERV) has been shown to result in the production of virus-neutralizing antibodies. The sera recognize two groups of epitopes, one located in the fusion peptide-proximal region (FPPR) and the second in the membrane-proximal external region (MPER) of p15E. Most interestingly, the epitopes in the MPER are similar to epitopes in the TM protein gp41 of human immunodeficiency virus type 1 (HIV-1) recognized by mAbs 2F5 and 4E10, which broadly neutralize HIV-1. To study which epitope and which antibody population are involved in the process of neutralization of PERV, this study generated a new antiserum in a goat using an elongated ectodomain of p15E. The immune serum neutralized PERV at a higher titre and recognized broader epitopes in the FPPR and MPER of p15E. For the first time, antibody subpopulations were isolated from this serum using affinity chromatography with immobilized proteins and peptides corresponding to the FPPR and MPER of p15E. Only the affinity-purified antibodies specifically binding the MPER neutralized PERV, indicating that, as in the case of HIV-1, the MPER is an important target of neutralizing activity. PMID:23223617

  18. Combined immunodeficiency develops with age in Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (ICF2).

    PubMed

    von Bernuth, Horst; Ravindran, Ethiraj; Du, Hang; Fröhler, Sebastian; Strehl, Karoline; Krämer, Nadine; Issa-Jahns, Lina; Amulic, Borko; Ninnemann, Olaf; Xiao, Mei-Sheng; Eirich, Katharina; Kölsch, Uwe; Hauptmann, Kathrin; John, Rainer; Schindler, Detlev; Wahn, Volker; Chen, Wei; Kaindl, Angela M

    2014-10-21

    The autosomal recessive immunodeficiency-centromeric instability-facial anomalies syndrome (ICF) is characterized by immunodeficiency, developmental delay, and facial anomalies. ICF2, caused by biallelic ZBTB24 gene mutations, is acknowledged primarily as an isolated B-cell defect. Here, we extend the phenotype spectrum by describing, in particular, for the first time the development of a combined immune defect throughout the disease course as well as putative autoimmune phenomena such as granulomatous hepatitis and nephritis. We also demonstrate impaired cell-proliferation and increased cell death of immune and non-immune cells as well as data suggesting a chromosome separation defect in addition to the known chromosome condensation defect. PMID:25330735

  19. Energetic Neutral Atom Precipitation (ENAP)

    NASA Technical Reports Server (NTRS)

    Tinsley, B. A.

    1988-01-01

    The Energetic Neutral Atom Precipitation experiment is scheduled to be flown on the Atmospheric Laboratory for Applications and Science (ATLAS 1) NASA mission. The objective of this experiment is to measure very faint emissions at nighttime arising from fluxes of energetic neutral atoms in the thermosphere. These energetic atoms have energies ranging up to about 50 keV, and arise from ions of hydrogen, helium, and oxygen trapped in the inner magnetosphere. Some of these ions become neutralized in charge exchange reactions with neutral hydrogen in the hydrogen geocorona that extends through the region. The ions are trapped on magnetic field lines which cross the equatorial plane at 2 to 6 earth radii distance, and they mirror at a range of heights on these field lines, extending down to the thermosphere at 500 km altitude. The ATLAS 1 measurements will not be of the neutral atoms themselves but of the optical emission produced by those on trajectories that intersect the thermosphere. The ENAP measurements are to be made using the Imaging Spectrometric Observatory (ISO) which is being flown on the ATLAS mission primarily for daytime spectral observations, and the ENAP measurements will all be nighttime measurements because of the faintness of the emissions and the relatively low level of magnetic activity expected.

  20. Protein Microarrays: A New Tool for the Study of Autoantibodies in Immunodeficiency

    PubMed Central

    Rosenberg, Jacob M.; Utz, Paul J.

    2015-01-01

    Autoimmunity is highly coincident with immunodeficiency. In a small but growing number of primary immunodeficiencies, autoantibodies are diagnostic of a given disease and implicated in disease pathogenesis. In order to improve our understanding of the role of autoantibodies in immunodeficiencies and to discover novel autoantibodies, new proteomic tools are needed. Protein microarrays have the ability to screen for reactivity to hundreds to many thousands of unique autoantigens simultaneously on a single chip using minimal serum input. Here, we review different types of protein microarrays and how they can be useful in framing the study of primary and secondary immunodeficiencies. PMID:25904912

  1. In Vivo Distribution of the Human Immunodeficiency Virus\\/Simian Immunodeficiency Virus Coreceptors: CXCR4, CCR3, and CCR5

    Microsoft Academic Search

    LINQI ZHANG; TIAN HE; ANDREW TALAL; GLORIA WANG; SARAH S. FRANKEL

    We have evaluated the in vivo distribution of the major human immunodeficiency virus\\/simian immunode- ficiency virus (HIV\\/SIV) coreceptors, CXCR4, CCR3, and CCR5, in both rhesus macaques and humans. T lymphocytes and macrophages in both lymphoid and nonlymphoid tissues are the major cell populations expressing HIV\\/SIV coreceptors, reaffirming that these cells are the major targets of HIV\\/SIV infection in vivo. In

  2. Cross-protection against mucosal simian immunodeficiency virus (SIVsm) challenge in human immunodeficiency virus type 2-vaccinated cynomolgus monkeys

    Microsoft Academic Search

    Lilian Walther-Jallow; Charlotta Nilsson; Johan So; Barbro Ma; Peter Biberfeld; Per Bo; Jonathan Heeney; Gunnel Biberfeld; Rigmor Thorstensson

    In this study we compared the efficacy of live attenuated human immunodeficiency virus type 2 (HIV-2) vaccine alone versus boosting with live non-pathogenic HIV-2 following priming with ALVAC HIV-2 (recombinant canarypox virus expressing HIV-2 env, gag and pol). Six monkeys were first inoculated intravenously with live HIV-2SBL-6669 and 7 to 10 months later were challenged intrarectally with 10 MID50 of

  3. Primary Immunodeficiency Diseases: An Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency

    PubMed Central

    Al-Herz, Waleed; Bousfiha, Aziz; Casanova, Jean-Laurent; Chapel, Helen; Conley, Mary Ellen; Cunningham-Rundles, Charlotte; Etzioni, Amos; Fischer, Alain; Franco, Jose Luis; Geha, Raif S.; Hammarström, Lennart; Nonoyama, Shigeaki; Notarangelo, Luigi Daniele; Ochs, Hans Dieter; Puck, Jennifer M.; Roifman, Chaim M.; Seger, Reinhard; Tang, Mimi L. K.

    2011-01-01

    We report the updated classification of primary immunodeficiency diseases, compiled by the ad hoc Expert Committee of the International Union of Immunological Societies. As compared to the previous edition, more than 15 novel disease entities have been added in the updated version. For each disorders, the key clinical and laboratory features are provided. This updated classification is meant to help in the diagnostic approach to patients with these diseases. PMID:22566844

  4. Market Share Game with adversarial Access providers : A Neutral and a Non-neutral Network

    E-print Network

    Paris-Sud XI, Université de

    . We analyze the effects of net neutrality on the charged price and offered QoS as behaviours of APsMarket Share Game with adversarial Access providers : A Neutral and a Non-neutral Network Analysis in the network-neutrality research. In this paper, we study the implication of non-neutrality on the competition

  5. Comparison of Search Engines Non-Neutral and Neutral Pierre Coucheney

    E-print Network

    Paris-Sud XI, Université de

    Comparison of Search Engines Non-Neutral and Neutral Behaviors Pierre Coucheney Inria Rennes to model two situations of a non-neutral search engine behavior, which can rank the link propositions ac Terms Economics, Neutrality, Search engines 1. INTRODUCTION Network neutrality has become a very hot

  6. Human monoclonal antibodies that neutralize vaccine and wild-type poliovirus strains.

    PubMed

    Puligedda, Rama Devudu; Kouiavskaia, Diana; Adekar, Sharad P; Sharma, Rashmi; Devi Kattala, Chandana; Rezapkin, Gennady; Bidzhieva, Bella; Dessain, Scott K; Chumakov, Konstantin

    2014-08-01

    An essential requirement for eradication of poliomyelitis is the elimination of circulating vaccine derived polioviruses (cVDPV) and polioviruses excreted by chronically infected individuals with immunodeficiencies (iVDPV). As part of a post-eradication risk management strategy, a human monoclonal antibody (mAb) therapeutic could play a role in halting excretion in asymptomatic carriers and could be used, in combination with vaccines and antiviral drugs, to protect polio-exposed individuals. Cross-neutralizing mAbs may be particularly useful, as they would reduce the number of mAbs needed to create a comprehensive PV therapeutic. We cloned a panel of IgG mAbs from OPV-vaccinated, IPV-boosted healthy subjects. Many of the mAbs had potent neutralizing activities against PV wild-type (WT) and Sabin strains, and two of the mAbs, 12F8 and 1E4, were significantly cross-reactive against types 1 and 2 and types 1 and 3, respectively. Mapping the binding epitopes using strains resistant to neutralization (escape mutants) suggested that cross-specific PV binding epitopes may primarily reside within the canyon region, which interacts with the cellular receptor molecule CD155 and the cross-neutralizing chimpanzee/human mAb, A12. Despite their close proximity, the epitopes for the 12F8 and 1E4 mAbs on Sabin 1 were not functionally identical to the A12 epitope. When tested together, 12F8 and 1E4 neutralized a diverse panel of clinically relevant PV strains and did not exhibit interference. Virus mutants resistant to the anti-poliovirus drug V-073 were also neutralized by the mAbs. The 12F8 and 1E4 mAbs may suitable for use as anti-PV therapeutics. PMID:24824031

  7. In Vitro Neutralization of Low Dose Inocula at Physiological Concentrations of a Monoclonal Antibody Which Protects Macaques against SHIV Challenge

    PubMed Central

    Davis, David; Koornstra, Wim; Fagrouch, Zahra; Verschoor, Ernst J.; Heeney, Jonathan L.; Bogers, Willy M. J. M.

    2013-01-01

    Background Passive transfer of antibodies can be protective in the simian human immunodeficiency virus (SHIV) – rhesus macaque challenge model. The human monoclonal antibody IgG1 b12 neutralizes human immunodeficiency type 1 (HIV-1) in vitro and protects against challenge by SHIV. Our hypothesis is that neutralizing antibodies can only completely inactivate a relatively small number of infectious virus. Methods And Findings We have used GHOST cell assays to quantify individual infectious events with HIV-1SF162 and its SHIV derivatives: the relatively neutralization sensitive SHIVSF162P4 isolate and the more resistant SHIVSF162P3. A plot of the number of fluorescent GHOST cells with increasing HIV-1SF162 dose is not linear. It is likely that with high-dose inocula, infection with multiple virus produces additive fluorescence in individual cells. In studies of the neutralization kinetics of IgG1 b12 against these isolates, events during the absorption phase of the assay, as well as the incubation phase, determine the level of neutralization. It is possible that complete inactivation of a virus is limited to the time it is exposed on the cell surface. Assays can be modified so that neutralization of these very low doses of virus can be quantified. A higher concentration of antibody is required to neutralize the same dose of resistant SHIVSF162P3 than the sensitive SHIVSF162P4. In the absence of selection during passage, the density of the CCR5 co-receptor on the GHOST cell surface is reduced. Changes in the CD4 : CCR5 density ratio influence neutralization. Conclusions Low concentrations of IgG1 b12 completely inactivate small doses of the neutralization resistant SHIV SF162P3. Assays need to be modified to quantify this effect. Results from modified assays may predict protection following repeated low-dose shiv challenges in rhesus macaques. It should be possible to induce this level of antibody by vaccination so that modified assays could predict the outcome of human trials. PMID:23977339

  8. A novel human anti-interleukin-1? neutralizing monoclonal antibody showing in vivo efficacy.

    PubMed

    Goh, Angeline X H; Bertin-Maghit, Sebastien; Ping Yeo, Siok; Ho, Adrian W S; Derks, Heidi; Mortellaro, Alessandra; Wang, Cheng-I

    2014-01-01

    The pro-inflammatory cytokine interleukin (IL)-1? is a clinical target in many conditions involving dysregulation of the immune system; therapeutics that block IL-1? have been approved to treat diseases such as rheumatoid arthritis (RA), neonatal onset multisystem inflammatory diseases, cryopyrin-associated periodic syndromes, active systemic juvenile idiopathic arthritis. Here, we report the generation and engineering of a new fully human antibody that binds tightly to IL-1? with a neutralization potency more than 10 times higher than that of the marketed antibody canakinumab. After affinity maturation, the derived antibody shows a>30-fold increased affinity to human IL-1? compared with its parent antibody. This anti-human IL-1? IgG also cross-reacts with mouse and monkey IL-1?, hence facilitating preclinical development. In a number of mouse models, this antibody efficiently reduced or abolished signs of disease associated with IL-1? pathology. Due to its high affinity for the cytokine and its potency both in vitro and in vivo, we propose that this novel fully human anti-IL-1? monoclonal antibody is a promising therapeutic candidate and a potential alternative to the current therapeutic arsenal. PMID:24671001

  9. Designer antigens for elicitation of broadly neutralizing antibodies against HIV

    PubMed Central

    Kok, Tuckweng; Gaeguta, Adriana; Finnie, John; Gorry, Paul R; Churchill, Melissa; Li, Peng

    2014-01-01

    Broadly neutralizing antibodies (bNAbs) are a consistent protective immune correlate in human immunodeficiency virus (HIV) patients as well as in passive immunotherapy studies. The inability to elicit bNAbs is the core reason underlining the repeated failures in traditional HIV vaccine research. Rare monoclonal bNAbs against HIV, however, have been produced. The significance of producing and studying more monoclonal bNAbs against HIV is underlined by its capability of defining critical epitopes for antigen designs aimed at the development of a serum-neutralizing HIV vaccine. In this regard, traditional antigen preparations have failed. There is a need to clearly advocate the concept, and systematic study, of more sophisticated ‘designer antigens' (DAGs), which carry epitopes that can lead to the elicitation of bNAbs. Using an extremely efficient cell-to-cell HIV infection model for the preparation of HIV prefusion intermediates, we have investigated a novel and systematic approach to produce (not screen for) potential bNAbs against HIV. We have established the concept and the experimental system for producing formaldehyde-fixed HIV DAGs that carry temperature-arrested prefusion intermediates. These prefusion intermediates are structures on the cell surface after viral attachment and receptor engagement but before fully functional viral entry. Using defined HIV prefusion DAGs, we have produced monoclonal antibodies (mAbs) specific to novel epitopes on HIV prefusion intermediates. These mAbs do not react with the static/native surface HIV or cellular antigens, but react with the DAGs. This is a paradigm shift from the current mainstream approach of screening elite patients' bNAbs. PMID:25505973

  10. Effects of anti-gp120 monoclonal antibodies on CD4 receptor binding by the env protein of human immunodeficiency virus type 1.

    PubMed Central

    Linsley, P S; Ledbetter, J A; Kinney-Thomas, E; Hu, S L

    1988-01-01

    Monoclonal antibodies (MAbs) to defined peptide epitopes on gp120 from human immunodeficiency virus type 1 were used to investigate the involvement of their epitopes in gp120 binding to the CD4 receptor. Recombinant vaccinia viruses were constructed that expressed either full-length gp120 (v-ED6), or a truncated gp120 lacking 44 amino acids at the carboxyl terminus (v-ED4). Binding of these glycoproteins to the CD4 receptor was detected directly with metabolically labeled gp120 or indirectly with the gp120 MAbs. Truncated gp120 from v-ED4 bound to CD4-positive cells less than 1/12 as well as gp120 from v-ED6, indicating that the C-terminal region of gp120, which is conserved in numerous isolates of human immunodeficiency virus type 1, is critical for CD4 binding. However, MAb 110-1, which recognizes a peptide contained in the region deleted from v-ED4 (amino acids 489 through 511), did not inhibit binding of gp120 to CD4. MAb 110-1 also reacted with gp120 bound to the CD4 receptor, indicating that the epitope for this antibody does not directly interact with CD4. A second MAb, 110-4, which recognizes a peptide epitope located between amino acids 303 and 323 and has potent viral neutralizing activity, also bound to gp120 on the CD4 receptor. Furthermore, pretreatment of gp120 with MAb 110-4 at concentrations approximately 1,000-fold higher than those required for complete virus neutralization inhibited subsequent CD4 binding by only about 65%. Taken together, these data suggest that neutralization mediated by antibody 110-4 does not result from binding of this MAb to the CD4-binding site of gp120. Images PMID:2458487

  11. 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

    ...information related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1.486...information related to infection with the human immunodeficiency virus to public health authorities. (a) In the...

  12. 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

    ...information related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1.486...information related to infection with the human immunodeficiency virus to public health authorities. (a) In the...

  13. 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

    ...information related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1.486...information related to infection with the human immunodeficiency virus to public health authorities. (a) In the...

  14. Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia

    MedlinePLUS

    ... X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (often shortened to XMEN ) On ... X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically known by the acronym ...

  15. Mechanism of Human Immunodeficiency Virus Type 1 Resistance to Monoclonal Antibody b12 That Effectively Targets the Site of CD4 Attachment?

    PubMed Central

    Wu, Xueling; Zhou, Tongqing; O'Dell, Sijy; Wyatt, Richard T.; Kwong, Peter D.; Mascola, John R.

    2009-01-01

    The region of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 that engages its primary cellular receptor CD4 forms a site of vulnerability to neutralizing antibodies. The monoclonal antibody b12 exploits the conservation and accessibility of the CD4-binding site to neutralize many, though not all, HIV-1 isolates. To understand the basis of viral resistance to b12, we used the atomic-level definition of b12-gp120 contact sites to study a panel of diverse circulating viruses. A combination of sequence analysis, computational modeling, and site-directed mutagenesis was used to determine the influence of amino acid variants on binding and neutralization by b12. We found that several substitutions within the dominant b12 contact surface, called the CD4-binding loop, mediated b12 resistance, and that these substitutions resided just proximal to the known CD4 contact surface. Hence, viruses varied in key b12 contact residues that are proximal to, but not part of, the CD4 contact surface. This explained how viral isolates were able to evade b12 neutralization while maintaining functional binding to CD4. In addition, some viruses were resistant to b12 despite minimal sequence variation at b12 contact sites. Such neutralization resistance usually could be reversed by alterations at residues thought to influence the quaternary configuration of the viral envelope spike. To design immunogens that elicit neutralizing antibodies directed to the CD4-binding site, researchers need to address the antigenic variation within this region of gp120 and the restricted access to the CD4-binding site imposed by the native configuration of the trimeric viral envelope spike. PMID:19692465

  16. Net neutrality: A user's guide

    Microsoft Academic Search

    Paul Ganley; Ben Allgrove

    2006-01-01

    Net neutrality is a complex issue that has generated intense levels of political discussion in the United States, but which has yet to attract significant attention from regulators in the UK. Nevertheless, the question of whether network operators should be prevented from blocking or prioritising certain network traffic or traffic from particular sources is a significant one for a wide range

  17. Net Neutrality... Seriously this Time

    Microsoft Academic Search

    Daniel J. Weitzner

    2008-01-01

    The net neutrality debate began a few years ago, prematurely, with overheated rhetoric about potential disasters for the Internet but little in the way of real threats requiring immediate government action. Beginning around May 2007, one of the largest ISPs in the US, Comcast, began a program of discriminatory blocking of certain Internet communications protocols. The blocking has focused on

  18. The Economics of Net Neutrality

    Microsoft Academic Search

    Robert W. Hahn; Scott Wallsten

    2006-01-01

    Robert Hahn and Scott Wallsten argue that mandating net neutrality, like most other forms of price regulation, is poor policy; instead, the government should focus on creating competition in the broadband market by liberalizing more spectrum and reducing entry barriers created by certain local regulations.

  19. Net Neutrality Paradox: Regulator's Dilemma

    Microsoft Academic Search

    Khalid Rafique; Chunhui Yuan; Muhammad Saeed

    2011-01-01

    Internet has emerged as a disruptive force for the conventional communication model. Internet evolution as the most effective communication medium paved the way for convergent communication services and new business models. The growing incidents of internet service discrimination (1) and service Blockade (2) has once again revived the debate of resolving the old issue of Network neutrality (3). The recent

  20. MSFC Skylab neutral buoyancy simulator

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The use of a neutral buoyancy simulator for developing extravehicular activity systems and for training astronauts in weightless activities is discussed. The construction of the facility and the operations are described. The types of tests and the training activities conducted in the simulator are reported. Photographs of the components of the simulator and actual training exercises are included.

  1. NEUTRALIZED DRIFT COMPRESSION EXPERIMENTS (NDCX)

    Microsoft Academic Search

    P. K. Roy; W. L. Waldron; S. S. Yu; P. A. Seidl; E. Henestroza; A. Anders; D. Baca; J. Barnard; F. M. Bieniosek; R. J. Briggs; C. Celata; J. Coleman; R. C. Davidson; P. C. Efthimion; S. Eylon; A. Friedman; E. P. Gilson; W. G. Greenway; D. P. Grote; I. Kaganovich; M. Leitner; B. G. Logan; H. Qin; L. L. Reginato; A. B. Sefkow; W. M. Sharp; C. Thoma; D. R. Welch

    Intense ion beams offer an attractive approach to heating dense matter uniformly to extreme conditions, because their energy deposition is nearly classical and volumetric. Simultaneous transverse and longitudinal beam compression in a neutralizing plasma medium, along with rapid beam acceleration, are being studied as a means of generating such beams for warm dense matter (WDM) and high energy density physics

  2. Self-neutralized ion beam

    SciTech Connect

    Salvadori, M. C.; Teixeira, F. S. [Institute of Physics, University of Sao Paulo, C.P. 66318, CEP 05315-970 Sao Paulo S.P. (Brazil); Nikolaev, A.; Savkin, K. P.; Oks, E. M. [High Current Electronics Institute, Russian Academy of Sciences, Tomsk 634055 (Russian Federation); Spaedtke, P. [Gesellschaft fuer Schwerionenforschung, D-64291 Darmstadt (Germany); Yu, K. M.; Brown, I. G. [Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States)

    2011-10-15

    A vacuum arc ion source provides high current beams of metal ions that have been used both for accelerator injection and for ion implantation, and in both of these applications the degree of space charge neutralization of the beam is important. In accelerator injection application, the beam from the ion source may be accelerated further (post-acceleration), redirected by a bending magnet(s), or focused with magnetic or electrostatic lenses, and knowledge of the beam space charge is needed for optimal design of the optical elements. In ion implantation application, any build-up of positive charge in the insulating targets must be compensated by a simultaneous flux of cold electrons so as to provide overall charge neutrality of the target. We show that in line-of-sight ion implantation using a vacuum arc ion source, the high current ion beam carries along its own background sea of cold electrons, and this copious source of electrons provides a ''self-neutralizing'' feature to the beam. Here we describe experiments carried out in order to demonstrate this effect, and we provide an analysis showing that the beam is space-charge-neutralized to a very high degree.

  3. Low energy neutral atom imaging

    SciTech Connect

    McComas, D.J.; Funsten, H.O.; Gosling, J.T.; Moore, K.R.; Thomsen, M.F.

    1992-01-01

    Energetic neutral atom (ENA) and low energy neutral atom (LENA) imaging of space plasmas are emerging new technology which promises to revolutionize the way we view and understand large scale space plasma phenomena and dynamics. ENAs and LENAs are produced in the magnetosphere by charge exchange between energetic and plasma ions and cold geocoronal neutrals. While imaging techniques have been previously developed for observing ENAs, with energies above several tens of keV, most of the ions found in the terrestrial magnetosphere have lower energies. We recently suggested that LENAs could be imaged by first converting the neutrals to ions and then electrostatically analyzing them to reject the UV background. In this paper we extend this work to examine in detail the sensor elements needed to make an LENA imager. These elements are (1) a biased collimator to remove the ambient plasma ions and electrons and set the azimuthal field-of-view; (2) a charge modifier to convert a portion of the incident LENAs to ions; (3) an electrostatic analyzer to reject UV light and set the energy passband; and (4) a coincidence detector to measure converted LENAs while rejecting noise and penetrating radiation. We also examine the issue of LENA imager sensitivity and describe ways of optimizing sensitivity in the various sensor components. Finally, we demonstrate in detail how these general considerations are implemented by describing one relatively straightforward design based on a hemispherical electrostatic analyzer.

  4. Consistent Patterns of Change during the Divergence of Human Immunodeficiency Virus Type 1 Envelope from That of the Inoculated Virus in Simian/Human Immunodeficiency Virus-Infected Macaques

    PubMed Central

    Blay, W.M.; Gnanakaran, S.; Foley, B.; Doria-Rose, N. A.; Korber, B. T.; Haigwood, N. L.

    2006-01-01

    We have analyzed changes to proviral Env gp120 sequences and the development of neutralizing antibodies (NAbs) during 1 year of simian/human immunodeficiency virus SHIV-89.6P infection in 11 Macaca nemestrina macaques. Seven macaques had significant env divergence from that of the inoculum, and macaques with greater divergence had higher titers of homologous NAbs. Substitutions in sequons encoding potential N-linked glycosylation sites (PNGs) were among the first to be established, although overall the total number of sequons did not increase significantly. The majority (19 of 23) of PNGs present in the inoculum were conserved in the sequences from all macaques. Statistically significant variations in PNGs occurred in multiple macaques within constrained regions we term “hot spots,” resulting in the selection of sequences more similar to the B consensus. These included additions on V1, the N-terminal side of V4, and the outer region of C2. Complex mutational patterns resulted in convergent PNG shifts in V2 and V5. Charge changes in Env V1V2, resulting in a net acidic charge, and a proline addition in V5 occurred in several macaques. Molecular modeling of the 89.6P sequence showed that the conserved glycans lie on the silent face of Env and that many are proximal to disulfide bonds, while PNG additions and shifts are proximal to the CD4 binding site. Nonsynonymous-to-synonymous substitution ratios suggest that these changes result from selective pressure. This longitudinal and cross-sectional study of mutations in human immunodeficiency virus (HIV) env in the SHIV background provides evidence that there are more constraints on the configuration of the glycan shield than were previously appreciated. PMID:16379001

  5. Presentation of Severe Combined Immunodeficiency with Respiratory Syncytial Virus and Pneumocystis Co-infection.

    PubMed

    Domínguez-Pinilla, Nerea; Allende-Martínez, Luis; Corral Sánchez, María Dolores; de Inocencio Arocena, Jaime; González-Granado, Luis Ignacio

    2015-04-01

    Severe combined immunodeficiency can cause severe, life-threatening viral, bacterial and fungal infections at an early age. We report a case of a 4-month-old boy with co-infection by respiratory syncytial virus and Pneumocystis jiroveci infection that led to recognition of severe combined immunodeficiency. PMID:25247585

  6. Induction of AIDS in Rhesus Monkeys by Molecularly Cloned Simian Immunodeficiency Virus

    Microsoft Academic Search

    Harry Kestler; Toshiaki Kodama; Douglas Ringler; Marta Marthas; Niels Pedersen; Andrew Lackner; Dean Regier; Prabhat Sehgal; Muthiah Daniel; Norval King; Ronald Desrosiers

    1990-01-01

    Better understanding of the pathogenesis of acquired immunodeficiency syndrome (AIDS) would be greatly facilitated by a relevant animal model that uses molecularly cloned virus of defined sequence to induce the disease. Such a system would also be of great value for AIDS vaccine research. An infectious molecular clone of simian immunodeficiency virus (SIV) was identified that induces AIDS in common

  7. Induction of Mucosal and Systemic Immunity to a Recombinant Simian Immunodeficiency Viral Protein

    Microsoft Academic Search

    T. Lehner; L. A. Bergmeier; C. Panagiotidi; L. Tao; R. Brookes; L. S. Klavinskis; P. Walker; J. Walker; R. G. Ward; L. Hussain; A. J. H. Gearing; S. E. Adams

    1992-01-01

    Heterosexual transmission through the cervico-vaginal mucosa is the principal route of human immunodeficiency virus (HIV) infection in Africa and is increasing in the United States and Europe. Vaginal immunization with simian immunodeficiency virus (SIV) had not yet been studied in nonhuman primates. Immune responses in macaques were investigated by stimulation of the genital and gut-associated lymphoid tissue with a recombinant,

  8. Immediate Zidovudine Treatment Protects Simian Immunodeficiency Virus-Infected Newborn Macaques against Rapid Onset of AIDS

    Microsoft Academic Search

    KOEN K. A. VAN ROMPAY; MOSES G. OTSYULA; MARTA L. MARTHAS; CHRISTOPHER J. MILLER; MICHAEL B. MCCHESNEY; ANDNIELS C. PEDERSEN

    1995-01-01

    Simian immunodeficiency virus (SIV) infection of newborn rhesus macaques is a practical animal model of pediatric AIDS. Intravenous inoculation of rhesus newborns with uncloned SIVmac resulted in a high virus load, no antiviral immune responses, severe immunodeficiency, and a high mortality rate within 3 months. In contrast, immediate oral zidovudine (AZT) treatment of SIV-inoculated rhesus newborns either prevented infection or

  9. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity

    Microsoft Academic Search

    John W. Shiver; Tong-Ming Fu; Ling Chen; Danilo R. Casimiro; Mary-Ellen Davies; Robert K. Evans; Zhi-Qiang Zhang; Adam J. Simon; Wendy L. Trigona; Sheri A. Dubey; Lingyi Huang; Virginia A. Harris; Romnie S. Long; Xiaoping Liang; Larry Handt; William A. Schleif; Lan Zhu; Daniel C. Freed; Natasha V. Persaud; Liming Guan; Kara S. Punt; Aimin Tang; Minchun Chen; Keith A. Wilson; Kelly B. Collins; Gwendolyn J. Heidecker; V. Rose Fernandez; Helen C. Perry; Joseph G. Joyce; Karen M. Grimm; James C. Cook; Paul M. Keller; Denise S. Kresock; Henryk Mach; Robert D. Troutman; Lynne A. Isopi; Donna M. Williams; Zheng Xu; Kathryn E. Bohannon; David B. Volkin; David C. Montefiori; Ayako Miura; Georgia R. Krivulka; Michelle A. Lifton; Marcelo J. Kuroda; Jörn E. Schmitz; Norman L. Letvin; Michael J. Caulfield; Andrew J. Bett; Rima Youil; David C. Kaslow; Emilio A. Emini

    2002-01-01

    Recent studies of human immunodeficiency virus type 1 (HIV-1) infection in humans and of simian immunodeficiency virus (SIV) in rhesus monkeys have shown that resolution of the acute viral infection and control of the subsequent persistent infection are mediated by the antiviral cellular immune response. We comparatively assessed several vaccine vector delivery systems-three formulations of a plasmid DNA vector, the

  10. Mutation of Unique Region of Bruton's Tyrosine Kinase in Immunodeficient XID Mice

    Microsoft Academic Search

    David J. Rawlings; Douglas C. Saffran; Satoshi Tsukada; David A. Largaespada; J. Christopher Grimaldi; Lucie Cohen; Randolph N. Mohr; J. Fernando Bazan; Maureen Howard; Neal G. Copeland; Nancy A. Jenkins; Owen N. Witte

    1993-01-01

    The cytoplasmic tyrosine kinase, Bruton's tyrosine kinase (Btk, formerly bpk or atk), is crucial for B cell development. Loss of kinase activity results in the human immunodeficiency, X-linked agammaglobulinemia, characterized by a failure to produce B cells. In the murine X-linked immunodeficiency (XID), B cells are present but respond abnormally to activating signals. The Btk gene, btk, was mapped to

  11. AIDS . Author manuscript Non-AIDS-defining deaths and immunodeficiency in the era of combination

    E-print Network

    Paris-Sud XI, Université de

    AIDS . Author manuscript Page /1 12 Non-AIDS-defining deaths and immunodeficiency in the era immunodeficiency is associated with the most frequent non-AIDS-defining causes of death, in the era of combination (71,230 person-years follow-up), 597 died, 333 (55.7 ) from non-AIDS-defining causes. Non-AIDS

  12. Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants

    Microsoft Academic Search

    Jennifer Powers; Diana M Truitt; Michael G Kishko; Janelle C Arthur; Fred W Peyerl; Marcelo J Kuroda; Darci A Gorgone; Michelle A Lifton; Carol I Lord; Vanessa M Hirsch; David C Montefiori; Angela Carville; Keith G Mansfield; Kevin J Kunstman; Steven M Wolinsky; Norman L Letvin; Dan H Barouch

    2005-01-01

    Viral escape from cytotoxic T lymphocytes (CTLs) can undermine immune control of human immunodeficiency virus 1. It is therefore important to assess the stability of viral mutations in CTL epitopes after transmission to naive hosts. Here we demonstrate the persistence of mutations in a dominant CTL epitope after transmission of simian immunodeficiency virus variants to major histocompatibility complex–matched rhesus monkeys.

  13. Human cancer growth and therapy in immunodeficient mouse models.

    PubMed

    Shultz, Leonard D; Goodwin, Neal; Ishikawa, Fumihiko; Hosur, Vishnu; Lyons, Bonnie L; Greiner, Dale L

    2014-07-01

    Since the discovery of the "nude" mouse more than 40 years ago, investigators have attempted to model human tumor growth in immunodeficient mice. Here, we summarize how the field has advanced over the ensuing years owing to improvements in the murine recipients of human tumors. These improvements include the discovery of the scid mutation and development of targeted mutations in the recombination-activating genes 1 and 2 (Rag1(null), Rag2(null)) that severely cripple the adaptive immune response of the murine host. More recently, mice deficient in adaptive immunity have been crossed with mice bearing targeted mutations designed to weaken the innate immune system, ultimately leading to the development of immunodeficient mice bearing a targeted mutation in the gene encoding the interleukin 2 (IL2) receptor common ? chain (IL2rg(null), also known in humans as cytokine receptor common subunit ?). The IL2rg(null) mutation has been used to develop several immunodeficient strains of mice, including the NOD-scid IL2rg(null) (NSG) strain. Using NSG mice as human xenograft recipients, it is now possible to grow almost all types of primary human tumors in vivo, including most solid tumors and hematological malignancies that maintain characteristics of the primary tumor in the patient. Programs to optimize patient-specific therapy using patient-derived xenograft tumor growth in NSG mice have been established at several institutions, including The Jackson Laboratory. Moreover, NSG mice can be engrafted with functional human immune systems, permitting for the first time the potential to study primary human tumors in vivo in the presence of a human immune system. PMID:24987146

  14. Increased titers of neutralizing antibodies after immunization with both envelope proteins of the porcine endogenous retroviruses (PERVs).

    PubMed

    Denner, Joachim; Mihica, Debora; Kaulitz, Danny; Schmidt, Christa-Maria

    2012-01-01

    Despite enormous difficulties to induce antibodies neutralizing HIV-1, especially broadly neutralizing antibodies directed against the conserved membrane proximal external region (MPER) of the transmembrane envelope protein, such antibodies can be easily induced in the case of gammaretroviruses, among them the porcine endogenous retroviruses (PERVs). In addition to neutralizing antibodies directed against the transmembrane envelope protein p15E, neutralizing antibodies were also induced by immunization with the surface envelope protein gp70. PERVs represent a special risk for xenotransplantation using pig tissues or organs since they are integrated in the genome of all pigs and infect human cells and a vaccine may protect from transmission to the recipient. To investigate the effect of simultaneous immunization with both proteins in detail, a study was performed in hamsters. Gp70 and p15E of PERV were produced in E. coli, purified and used for immunization. All animals developed binding antibodies against the antigens used for immunization. Sera from animals immunized with p15E recognized epitopes in the MPER and the fusion peptide proximal region (FPPR) of p15E. One MPER epitope showed a sequence homology to an epitope in the MPER of gp41 of HIV-1 recognized by broadly neutralizing antibodies found in HIV infected individuals. Neutralizing antibodies were detected in all sera. Most importantly, sera from animals immunized with gp70 had a higher neutralizing activity when compared with the sera from animals immunized with p15E and sera from animals immunized with gp70 together with p15E had a higher neutralizing activity compared with sera from animals immunized with each antigen alone. These immunization studies are important for the development of vaccines against other retroviruses including the human immunodeficiency virus HIV-1. PMID:23126255

  15. Reticular erythematous mucinosis associated with human immunodeficiency virus infection.

    PubMed

    Daudén, E; Peñas, P F; Buezo, G F; Fraga, J; García-Diez, A

    1995-01-01

    We report the case of a 56-year-old woman with reticular erythematous mucinosis (REM). During her workup infection with the human immunodeficiency virus (HIV) was detected. She developed a cerebral toxoplasmosis, salmonella sp. bacteremia and oral ulcerations with the presence of type I herpes simplex virus and cytomegalovirus. The relation of REM with the deposition of mucin in AIDS patients' bone marrow and HIV infection is discussed. To our knowledge, this is the first report where REM is associated with HIV disease. PMID:8520066

  16. Beware the lymphopenia: a case of severe combined immunodeficiency.

    PubMed

    Mehr, Sam; Kakakios, Alyson; Shaw, Peter; Webster, Richard; Kemp, Andrew

    2011-08-01

    We present a case of a 2-month-old boy with partially treated meningitis and suspected Pneumocystis carinii pneumonia. A full blood count revealed profound lymphopenia. The child was diagnosed with adenosine deaminase deficiency, a rare cause of severe combined immunodeficiency (SCID). SCID is an immunological emergency and must be considered in any lymphopaenic infant with opportunistic infection. We discuss adenosine deaminase-deficient SCID, which can involve multiple systems and in which other treatment options apart from bone marrow transplant are available. PMID:21843190

  17. Human immunodeficiency virus can productively infect cultured human glial cells.

    PubMed Central

    Cheng-Mayer, C; Rutka, J T; Rosenblum, M L; McHugh, T; Stites, D P; Levy, J A

    1987-01-01

    Six isolates of the human immunodeficiency virus (HIV) showed differences in their ability to productively infect glioma-derived cell lines and early-passage human brain cell cultures. Susceptibility to HIV infection correlated well with the expression of the astrocyte marker glial fibrillary acidic protein. The CD4 molecule was expressed on some, but not all, of the brain-derived cells; however, no correlation was observed between CD4 protein expression and susceptibility to virus infection. The results show that HIV can productively infect human brain cells, particularly those of glial origin, and suggest that these cell types in the brain can harbor the virus. Images PMID:3472222

  18. Giardiasis as a cause of hypokalemic myopathy in congenital immunodeficiency.

    PubMed

    Genovese, A; Spadaro, G; Santoro, L; Gasparo Rippa, P; Onorati, A M; Marone, G

    1996-01-01

    Hypokalemic myopathy may occur in several infections. We report a case of severe and transient myopathy secondary to hypokalemia induced by chronic intestinal infection with Giardia lamblia in a patient with common variable hypogammaglobulinemia. Hypokalemic myopathy is documented by serum enzymes, electromyography (reduction in the number of voluntarily activated motor unit action potentials and an increase in polyphasic motor unit action potentials, and pathological changes (hematoxylin-eosin, ATPase staining). The case reported involves hypokalemic myopathy induced by giardiasis in a patient with primary immunodeficiency; the histopathological changes observed in a skin/muscle biopsy from this patient are described for the first time. PMID:8856367

  19. Cytomegalovirus Colitis with Common Variable Immunodeficiency and Crohn's Disease

    PubMed Central

    Ünal, Betül; Ba?sorgun, Cumhur ?brahim; Çil Gönülcü, Sinem; Uçar, Asl?; Çelik, Fatih; Elpek, Gülsüm Özlem

    2015-01-01

    Here we present an eleven-year-old male patient who had been diagnosed with common variable immunodeficiency (CVID) three years ago due to recurrent sinopulmonary infections. Two years later he had been diagnosed with Crohn's disease (CD) due to diarrhea episodes which were unresponsive to the treatment. Depending on the active gastrointestinal bleeding and perforation he underwent total colectomy. Despite immunoglobulin and antiviral therapies, general condition of patient deteriorated and he died in the postoperative seventh day. Laboratory analysis was seronegative. CMV inclusion containing cells were detected in postmortem biopsies taken from liver, lungs, and lymph nodes. PMID:25802525

  20. Electrolyte disorders and renal dysfunction in acquired immunodeficiency syndrome patients.

    PubMed Central

    Peter, S. A.

    1991-01-01

    A total of 81 Latino and African American patients with acquired immunodeficiency syndrome (AIDS) in an innercity hospital were studied retrospectively to determine the frequency of electrolyte disorders and renal dysfunction in this syndrome. Of these 81 patients, 28.4% had hyponatremia, 17.3% had hypokalemia, and 4.9% had hyperkalemia without renal failure. Five (6.2%) patients had renal failure; four of these were Latino. The results confirm that electrolyte abnormalities are a common feature of AIDS and that Latino patients are also susceptible to AIDS-associated nephropathy. PMID:1800763

  1. First molecular characterization of feline immunodeficiency virus in Turkey.

    PubMed

    O?uzo?lu, Tuba Ci?dem; Timurkan, Mehmet Ozkan; Muz, Dilek; Kudu, Ay?egül; Numanbayraktaro?lu, Ba?ak; Sadak, Seda; Burgu, Ibrahim

    2010-11-01

    In this study, strains of feline immunodeficiency virus (FIV), designated TR-D, TR-Mo and TR-Mi, isolated from three cats in Turkey, were characterized. PCR products (859 bp) from the envelope (env) gene region were amplified and sequenced, and possible geographical differences in the env gene region of Turkish FIV strains are discussed. Phylogenetic analysis of two strains showed that FIV subtype B was present in Turkey. Phylogenetic analysis showed that one new Turkish FIV strain occupies a separate branch from known clusters (subtypes A to E) from the USA, Canada, Europe and Japan. PMID:20972598

  2. [Genito-urinary tuberculosis in acquired immunodeficiency syndrome].

    PubMed

    Jara Rascón, J; Herranz Amo, F; Saiz Carrero, A; Diez Cordero, J M; Moncada Iribarren, I; Hernández Fernández, C; Verdú Tartajo, F

    1989-01-01

    Tuberculosis is being described as a highly associated entity with the acquired immunodeficiency syndrome (AIDS) in countries or geographical areas where this entity is endemic, even becoming its first clinical manifestation. Two cases of prostatic abscess are presented in patients with anti-HIV antibodies, who are parenteral drug users. In one of them, his genitourinary tuberculous infection was the first sign of AIDS. In the other, a previous association with tuberculous meningitis was found. The evolution and pathogenicity of tuberculous genitourinary in AIDS patients is discussed. PMID:2711912

  3. 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.

  4. 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

    ...FDA-2005D-0261) Guidance for Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency...entitled ``Guidance for Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency...Immunodeficiency Virus Type 1 (HIV-1) Nucleic Acid Test (NAT) and Hepatitis C Virus...

  5. An Orphan Seven-Transmembrane Domain Receptor Expressed Widely in the Brain Functions as a Coreceptor for Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus

    Microsoft Academic Search

    AIMEE L. EDINGER; TREVOR L. HOFFMAN; MATTHEW SHARRON; BENHUR LEE; YANJI YI; WONKYU CHOE; DENNIS L. KOLSON; BRANKA MITROVIC; YIQING ZHOU; DARYL FAULDS; RONALD G. COLLMAN; JOSEPH HESSELGESSER; RICHARD HORUK; ROBERT W. DOMS

    1998-01-01

    Both CD4 and an appropriate coreceptor are necessary for infection of cells by human immunodeficiency virus type 1 (HIV-1) and most strains of HIV-2. The chemokine receptors CCR5 and CXCR4 are the major HIV-1 coreceptors, although some virus strains can also utilize alternative coreceptors such as CCR3 to infect cells. In contrast, most if not all simian immunodeficiency virus (SIV)

  6. Selective Expansion of Viral Variants following Experimental Transmission of a Reconstituted Feline Immunodeficiency Virus Quasispecies

    PubMed Central

    Willett, Brian J.; Kraase, Martin; Logan, Nicola; McMonagle, Elizabeth; Varela, Mariana; Hosie, Margaret J.

    2013-01-01

    Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV), a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1) or diverse (Group 2) challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point) being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development. PMID:23372784

  7. Cytokine Polymorphisms are Associated with Poor Sleep Maintenance in Adults Living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

    PubMed Central

    Lee, Kathryn A.; Gay, Caryl; Pullinger, Clive R.; Hennessy, Mary Dawn; Zak, Rochelle S.; Aouizerat, Bradley E.

    2014-01-01

    Study Objectives: Cytokine activity and polymorphisms have been associated with sleep outcomes in prior animal and human research. The purpose of this study was to determine whether circulating plasma cytokines and cytokine polymorphisms are associated with the poor sleep maintenance commonly experienced by adults living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Design: Cross-sectional descriptive study. Setting: HIV clinics and community sites in the San Francisco Bay area. Participants: A convenience sample of 289 adults (193 men, 73 women, and 23 transgender) living with HIV/AIDS. Interventions: None. Measurements and Results: A wrist actigraph was worn for 72 h to estimate the percentage of wake after sleep onset (WASO%) and total sleep time (TST), plasma cytokines were analyzed, and genotyping was conducted for 15 candidate genes involved in cytokine signaling: interferon-gamma (IFNG), IFNG receptor 1 (IFNGR1), interleukins (IL1B, IL1R2, IL1R2, IL2, IL4, IL6, IL8, IL10, IL13, IL17A), nuclear factor of kappa light polypeptide gene enhancer in B cells (NFKB1 and NFKB2), and tumor necrosis factor-alpha (TNFA). Controlling for demographic variables such as race and sex, and clinical variables such as CD4+ count and medications, higher WASO% was associated with single nucleotide polymorphisms (SNPs) of IL1R2 rs11674595 and TNFA rs1041981 and less WASO% was associated with IL2 rs2069776. IL1R2 rs11674595 and TNFA rs1041981 were also associated with short sleep duration. Conclusions: This study strengthens the evidence for an association between inflammation and sleep maintenance problems. In this chronic illness population, cytokine polymorphisms associated with wake after sleep onset provide direction for intervention research aimed at comparing anti-inflammatory mechanisms with hypnotic agents for improving sleep maintenance and total sleep time. Citation: Lee KA; Gay C; Pullinger CR; Hennessy MD; Zak RS; Aouizerat BE. Cytokine polymorphisms are associated with poor sleep maintenance in adults living with human immunodeficiency virus/acquired immunodeficiency syndrome. SLEEP 2014;37(3):453-463. PMID:24587567

  8. Primary Immunodeficiency Diseases: An Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency

    PubMed Central

    Al-Herz, Waleed; Bousfiha, Aziz; Casanova, Jean-Laurent; Chatila, Talal; Conley, Mary Ellen; Cunningham-Rundles, Charlotte; Etzioni, Amos; Franco, Jose Luis; Gaspar, H. Bobby; Holland, Steven M.; Klein, Christoph; Nonoyama, Shigeaki; Ochs, Hans D.; Oksenhendler, Erik; Picard, Capucine; Puck, Jennifer M.; Sullivan, Kate; Tang, Mimi L. K.

    2014-01-01

    We report the updated classification of primary immunodeficiencies (PIDs) compiled by the Expert Committee of the International Union of Immunological Societies. In comparison to the previous version, more than 30 new gene defects are reported in this updated version. In addition, we have added a table of acquired defects that are phenocopies of PIDs. For each disorder, the key clinical and laboratory features are provided. This classification is the most up-to-date catalog of all known PIDs and acts as a current reference of the knowledge of these conditions and is an important aid for the molecular diagnosis of patients with these rare diseases. PMID:24795713

  9. Neutral matter in planetary nebulae

    NASA Technical Reports Server (NTRS)

    Dinerstein, Harriet L.

    1991-01-01

    A review of current studies of neutral envelopes is presented with particular attention given to the use of the envelopes as test cases for understanding the ionization and thermal structure of photodissociation regions. The study of near-IR H2 emission is discussed with detailed spectra given for a few planetary nebulae, and airborne observations of far-IR atomic lines are discussed. These two methods can discern photodissociation regions with warm gas and UV flux is fairly prominent. The use of resonance-absorption-line spectroscopy is also reviewed with respect to the analysis of the Na D lines, and thereby allows the measurement of integrated columns of material through the shell. The methods provide evidence for the notion that planetary nebulae consist of more than just ionized material; large amounts of neutral and molecular material are being confirmed, which has important implications for the mass-loss episode of the nebulae.

  10. Optimization of neutral atom imagers

    NASA Astrophysics Data System (ADS)

    Shappirio, M.; Coplan, M.; Balsamo, E.; Chornay, D.; Collier, M.; Hughes, P.; Keller, J.; Ogilvie, K.

    2008-12-01

    : The interactions between plasma structures and neutral atom populations in interplanetary space can be effectively studied with energetic neutral atom imagers. For neutral atoms with energies less than 1 keV, the most efficient detection method that preserves direction and energy information is conversion to negative ions on surfaces. We have examined a variety of surface materials and conversion geometries in order to identify the factors that determine conversion efficiency. For chemically and physically stable surfaces smoothness is of primary importance while properties such as work function have no obvious correlation to conversion efficiency. For the noble metals, tungsten, silicon, and graphite with comparable smoothness, conversion efficiency varies by a factor of two to three. We have also examined the way in which surface conversion efficiency varies with the angle of incidence of the neutral atom and have found that the highest efficiencies are obtained at angles of incidence greater then 80°. The conversion efficiency of silicon, tungsten and graphite were examined most closely and the energy dependent variation of conversion efficiency measured over a range of incident angles. We have also developed methods for micromachining silicon in order to reduce the volume to surface area over that of a single flat surface and have been able to reduce volume to surface area ratios by up to a factor of 60. With smooth micro-machined surfaces of the optimum geometry, conversion efficiencies can be increased by an order of magnitude over instruments like LENA on the IMAGE spacecraft without increase the instruments mass or volume. Work was supported by grant ACT-05-40 from the ESTO office of NASA

  11. Optimization of Neutral Atom Imagers

    NASA Technical Reports Server (NTRS)

    Shappirio, M.; Coplan, M.; Balsamo, E.; Chornay, D.; Collier, M.; Hughes, P.; Keller, J.; Ogilvie, K.; Williams, E.

    2008-01-01

    The interactions between plasma structures and neutral atom populations in interplanetary space can be effectively studied with energetic neutral atom imagers. For neutral atoms with energies less than 1 keV, the most efficient detection method that preserves direction and energy information is conversion to negative ions on surfaces. We have examined a variety of surface materials and conversion geometries in order to identify the factors that determine conversion efficiency. For chemically and physically stable surfaces smoothness is of primary importance while properties such as work function have no obvious correlation to conversion efficiency. For the noble metals, tungsten, silicon, and graphite with comparable smoothness, conversion efficiency varies by a factor of two to three. We have also examined the way in which surface conversion efficiency varies with the angle of incidence of the neutral atom and have found that the highest efficiencies are obtained at angles of incidence greater then 80deg. The conversion efficiency of silicon, tungsten and graphite were examined most closely and the energy dependent variation of conversion efficiency measured over a range of incident angles. We have also developed methods for micromachining silicon in order to reduce the volume to surface area over that of a single flat surface and have been able to reduce volume to surface area ratios by up to a factor of 60. With smooth micro-machined surfaces of the optimum geometry, conversion efficiencies can be increased by an order of magnitude over instruments like LENA on the IMAGE spacecraft without increase the instruments mass or volume.

  12. Theoretical investigation of neutral francium

    Microsoft Academic Search

    E. Biémont; P. Quinet; V. Van Renterghem

    1998-01-01

    Energy levels of neutral francium are investigated in the Ritz formalism along the Rydberg series up to n = 30. Transition probabilities are calculated for the s-p and p-d transitions. Core-polarization effects are included in the model adopted. The validity of the approach has been tested by comparison with the laser lifetime measurements available for the 70953-4075\\/31\\/24\\/012\\/img7 and 70953-4075\\/31\\/24\\/012\\/img8 states

  13. Plasma sources for spacecraft neutralization

    NASA Technical Reports Server (NTRS)

    Davis, V. A.; Katz, I.; Mandell, M. J.

    1990-01-01

    The principles of the operation of plasma sources for the neutralization of the surface of a spacecraft traveling in the presence of hot plasma are discussed with special attention given to the hollow-cathode-based plasma contactors. Techiques are developed that allow the calculation of the potentials and particle densities in the near environment of a hollow cathode plasma contactor in both the test tank and the LEO environment. The techniques and codes were validated by comparison of calculated and measured results.

  14. 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 ?2 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.

  15. When less is more: primary immunodeficiency with an autoinflammatory kick

    PubMed Central

    Giannelou, Angeliki; Zhou, Qing; Kastner, Daniel L.

    2014-01-01

    Purpose of review Next-generation sequencing is revolutionizing the molecular taxonomy of human disease. Recent studies of patients with unexplained autoinflammatory disorders reveal germline genetic mutations that target important regulators of innate immunity. Recent findings Whole-exome analyses of previously undiagnosed patients have catalyzed the recognition of two new disease genes. First, a phenotypic spectrum, including livedo racemosa, fever with early-onset stroke, polyarteritis nodosa, and Sneddon syndrome, is caused by loss-of-function mutations in cat eye syndrome chromosome region, candidate 1 (CECR1), encoding adenosine deaminase 2. Adenosine deaminase 2 is a secreted protein expressed primarily in myeloid cells, and a regulator of macrophage differentiation and endothelial development. Disease-associated mutations impair anti-inflammatory M2 macrophage differentiation. Second, patients presenting with cold-induced urticaria, granulomatous rash, autoantibodies, and common variable immunodeficiency, or with blistering skin lesions, bronchiolitis, enterocolitis, ocular inflammation, and mild immunodeficiency harbor distinct mutations in phospholipase C?2, encoding a signaling molecule expressed in natural killer cells, mast cells, and B lymphocytes. These mutations inhibit the function of a phospholipase C?2 autoinhibitory domain, causing increased or constitutive signaling. Summary These findings underscore the power of next-generation sequencing, demonstrating how the primary deficiency of key molecular regulators or even regulatory motifs may lead to autoinflammation, and suggesting a possible role for cat eye syndrome chromosome region, candidate 1 and phospholipase C?2 in common diseases. PMID:25337682

  16. Macrophages prevent human red blood cell reconstitution in immunodeficient mice

    PubMed Central

    Hu, Zheng; Van Rooijen, Nico

    2011-01-01

    An animal model supporting human erythropoiesis will be highly valuable for assessing the biologic function of human RBCs under physiologic and disease settings, and for evaluating protocols of in vitro RBC differentiation. Herein, we analyzed human RBC reconstitution in NOD/SCID or NOD/SCID/?c?/? mice that were transplanted with human CD34+ fetal liver cells and fetal thymic tissue. Although a large number of human CD45?CD71+ nucleated immature erythroid cells were detected in the bone marrow, human RBCs were undetectable in the blood of these mice. Human RBCs became detectable in blood after macrophage depletion but disappeared again after withdrawal of treatment. Furthermore, treatment with human erythropoietin and IL-3 significantly increased human RBC reconstitution in macrophage-depleted, but not control, humanized mice. Significantly more rapid rejection of human RBCs than CD47-deficient mouse RBCs indicates that mechanisms other than insufficient CD47-SIRP? signaling are involved in human RBC xenorejection in mice. All considered, our data demonstrate that human RBCs are highly susceptible to rejection by macrophages in immunodeficient mice. Thus, strategies for preventing human RBC rejection by macrophages are required for using immunodeficient mice as an in vivo model to study human erythropoiesis and RBC function. PMID:21926352

  17. Perisinusoidal cell hypertrophy in a patient with acquired immunodeficiency syndrome.

    PubMed

    Kossaifi, T; Dupon, M; Le Bail, B; Lacut, Y; Balabaud, C; Bioulac-Sage, P

    1990-08-01

    A 33-year-old heterosexual white man underwent a liver biopsy for determination of mild elevation of aminotransferase levels (aspartate aminotransferase, two times; alanine aminotransferase, three times). The patient had acquired immunodeficiency syndrome (stage IVC2) with tuberculosis of the lymph nodes. Antibody to hepatitis B surface antigen and antibody to hepatitis B core antigen were positive. Syphillis tests were positive. Liver architecture was normal; sinusoids were dilated with perisinusoidal, centrilobular, and portal fibrosis. On a 1-micron-thick section and under electron microscopy, perisinusoidal cells appeared to be massively loaded with lipids, while endothelial cells contained numerous dense bodies. Some hepatocytes presented evidence of cell damage. Sinusoids were infiltrated by an increased number of lymphocytes and macrophages. This patient who had recently been treated for tuberculosis was not taking extra vitamin A. He had no disease so far reported as being associated with perisinusoidal cell hypertrophy. This case and others are evidence that acquired immunodeficiency syndrome represents another cause of perisinusoidal cell hypertrophy in which there is no documented hypervitaminosis A. PMID:2375662

  18. Lentiviral vectors for the treatment of primary immunodeficiencies.

    PubMed

    Farinelli, Giada; Capo, Valentina; Scaramuzza, Samantha; Aiuti, Alessandro

    2014-07-01

    In the last years important progress has been made in the treatment of several primary immunodeficiency disorders (PIDs) with gene therapy. Hematopoietic stem cell (HSC) gene therapy indeed represents a valid alternative to conventional transplantation when a compatible donor is not available and recent success confirmed the great potential of this approach. First clinical trials performed with gamma retroviral vectors were promising and guaranteed clinical benefits to the patients. On the other hand, the outcome of severe adverse events as the development of hematological abnormalities highlighted the necessity to develop a safer platform to deliver the therapeutic gene. Self-inactivating (SIN) lentiviral vectors (LVVs) were studied to overcome this hurdle through their preferable integration pattern into the host genome. In this review, we describe the recent advancements achieved both in vitro and at preclinical level with LVVs for the treatment of Wiskott-Aldrich syndrome (WAS), chronic granulomatous disease (CGD), ADA deficiency (ADA-SCID), Artemis deficiency, RAG1/2 deficiency, X-linked severe combined immunodeficiency (?chain deficiency, SCIDX1), X-linked lymphoproliferative disease (XLP) and immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. PMID:24619149

  19. Cernunnos/XLF Deficiency: A Syndromic Primary Immunodeficiency.

    PubMed

    Cipe, Funda Erol; Aydogmus, Cigdem; Babayigit Hocaoglu, Arzu; Kilic, Merve; Kaya, Gul Demet; Yilmaz Gulec, Elif

    2014-01-01

    Artemis, DNA ligase IV, DNA protein kinase catalytic subunit, and Cernunnos/XLF genes in nonhomologous end joining pathways of DNA repair mechanisms have been identified as responsible for radiosensitive SCID. Here, we present a 3-year-old girl patient with severe growth retardation, bird-like face, recurrent perianal abscess, pancytopenia, and polydactyly. Firstly, she was thought as Fanconi anemia and spontaneous DNA breaks were seen on chromosomal analysis. After that DEB test was found to be normal and Fanconi anemia was excluded. Because of that she had low IgG and IgA levels, normal IgM level, and absence of B cells in peripheral blood; she was considered as primary immunodeficiency, Nijmegen breakage syndrome. A mutation in NBS1 gene was not found; then Cernunnos/XLF deficiency was investigated due to clinical similarities with previously reported cases. Homozygous mutation in Cernunnos/XLF gene (NHEJ1) was identified. She is now on regular IVIG prophylaxis and has no new infection. Fully matched donor screening is in progress for bone marrow transplantation which is curative treatment of the disease. In conclusion, the patients with microcephaly, bird-like face, and severe growth retardation should be evaluated for hypogammaglobulinemia and primary immunodeficiency diseases. PMID:24511403

  20. Endocrine complications associated with human immunodeficiency virus infection.

    PubMed

    Etzel, J V; Brocavich, J M; Torre, M

    1992-08-01

    The causes and management of endocrine disorders associated with human immunodeficiency virus (HIV) infection are reviewed. Endocrine disorders observed in HIV-positive patients include adrenal abnormalities, hyporeninemic hypoaldosteronism, pituitary insufficiency, pancreatic abnormalities, thyroid and parathyroid disorders, and testicular abnormalities. Opportunistic pathogens implicated in these disorders include cytomegalovirus, Cryptococcus, Toxoplasma, mycobacteria, Candida, and Aspergillus. Neoplasma such as Kaposi's sarcoma and lymphoma can also cause endocrine abnormalities. Several drugs used in patients with the acquired immunodeficiency syndrome (AIDS) are associated with the development of endocrine disorders. These drugs include ketoconazole, itraconazole, rifampin, vidarabine, pentamidine, trimethoprim-sulfamethoxazole, didanosine, and ganciclovir. Severe patient debilitation can contribute to the development of endocrine abnormalities. Monitoring of adrenal gland function may be prudent in HIV-infected patients who have nonspecific symptoms of adrenal insufficiency. If adrenal insufficiency is diagnosed, replacement therapy with oral hydrocortisone is required. Administration of fludrocortisone can rapidly alleviate the signs and symptoms of hyporeninemic hypoaldosteronism. Fluid restriction is the first step in managing the pituitary abnormality known as the syndrome of inappropriate secretion of antidiuretic hormone. Drug-induced endocrine abnormalities often resolve after withdrawal of the offending agent. Endocrine complications in HIV-infected patients may be caused by infection, malignancy, or drugs. Adjusting or instituting drug therapy may be necessary to control symptomatic endocrine abnormalities. PMID:1511543

  1. Oral lesions: A true clinical indicator in human immunodeficiency virus.

    PubMed

    Saini, Rajiv

    2011-07-01

    From the onset of the human immunodeficiency virus (HIV) epidemic over 20 years ago (since the appearance of the first cases of contamination by the HIV virus in the 1980s), more than 60 million people have become infected and more than 20 million people have died. An estimated 15,000 new infections occur each day, with more than 95% of these in developing countries. The distinctive characteristic in the pathogenesis of HIV/acquired immunodeficiency syndrome is that the primary target cell for HIV is immune cells bearing the CD4 marker at their surface, and the CD4 cell count and viral load have been used lately as the most important laboratory parameters to evaluate the evolution of the disease. Oral lesions are common (30-80%) in patients infected by the HIV virus and may indicate an impairment in the patient's general health status and, consequently, a poor prognosis. Oral manifestations can suggest decreased cluster-differentiated (CD4+) T cell count and increased viral load, which might also aid in diagnosis, progression, and prognosis of the disease. At the tertiary level of oral care, a dentist should be available to make definitive diagnoses of oral lesions and provide professional oral services such as prophylaxis, restorations, biopsies, and the prescription of appropriate medication. PMID:22346226

  2. Inherited and acquired immunodeficiencies underlying tuberculosis in childhood.

    PubMed

    Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; El-Baghdadi, Jamila; Camcioglu, Yildiz; Parvaneh, Nima; El Azbaoui, Safaa; Agader, Aomar; Hassani, Amal; El Hafidi, Naima; Mrani, Nidal Alaoui; Jouhadi, Zineb; Ailal, Fatima; Najib, Jilali; Reisli, Ismail; Zamani, Adil; Yosunkaya, Sebnem; Gulle-Girit, Saniye; Yildiran, Alisan; Cipe, Funda Erol; Torun, Selda Hancerli; Metin, Ayse; Atikan, Basak Yildiz; Hatipoglu, Nevin; Aydogmus, Cigdem; Kilic, Sara Sebnem; Dogu, Figen; Karaca, Neslihan; Aksu, Guzide; Kutukculer, Necil; Keser-Emiroglu, Melike; Somer, Ayper; Tanir, Gonul; Aytekin, Caner; Adimi, Parisa; Mahdaviani, Seyed Alireza; Mamishi, Setareh; Bousfiha, Aziz; Sanal, Ozden; Mansouri, Davood; Casanova, Jean-Laurent; Abel, Laurent

    2015-03-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-? immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey. PMID:25703555

  3. Adrenal adenomatoid tumor in a patient with human immunodeficiency virus.

    PubMed

    Phitayakorn, Roy; Maclennan, Gregory; Sadow, Peter; Wilhelm, Scott

    2011-04-01

    We present the clinical course of a patient with human immunodeficiency virus and an adrenal adenomatoid tumor (AAT). We describe the clinical course and laboratory, radiographic, and microscopic findings of a patient with human immunodeficiency virus (HIV) and an adenomatoid tumor of the right adrenal gland. A review of the literature was also done via electronic searches through PubMed for articles from 1965 to 2008 that contained the following search terms, adenomatoid tumor limited to the English language only. A 22 year-old African-American male with HIV was incidentally found to have a hypermetabolic right adrenal mass. The patient underwent laparoscopic adrenalectomy and the mass had morphological and immunohistochemical features that were consistent with an AAT. A review of the medical literature reveals that almost all cases of AAT were in male patients (96%) with a mean age of 41±11 years (range=22-64) with no significant difference in laterality (right side=46%, left side=50%, unknown=4%). AAT have an average size of 4.2±3.5 cm (range=0.5-14.3 cm). Pre-operative imaging studies do not appear to be able to reliably distinguish AAT from other types of adrenocortical tumors. For reasons that require further research, AAT typically occur in male patients and may be associated with immunosuppression. AAT can be safely removed laparoscopically with no evidence of long-term recurrence even with tumor extension beyond the adrenal capsule. PMID:21769320

  4. Newborn screening for severe combined immunodeficiency (SCID): a review.

    PubMed

    Huang, Hai; Manton, Kenneth G

    2005-01-01

    Because prompt intervention may prevent complications, early diagnosis is important in many inherited metabolic diseases. Early diagnosis of Severe Combined Immunodeficiency (SCID) is critical - because chances for successful treatment are highest for infants who have not yet experienced severe opportunistic infections. SCID is a rare disease that can be detected in newborn infants (i.e., those more or equal 1 month of age) by automated blood count and manual differential. Early diagnosis of SCID is rare since, because estimates of the incidence rate range from one in 50,000 to 100,000 births, most pediatricians do not routinely count white blood cells in newborns. Tests for T-cell lymphopenia (TCLP) using dried blood spots (DBS) could be used to identify children with SCID - as well as for other immunodeficiencies that would not be apparent until after the child developed an infection. Screening newborns for SCID would allow early diagnosis and treatment -- as well as genetic counseling for the family. PMID:15769602

  5. Ion-beam Plasma Neutralization Interaction Images

    SciTech Connect

    Igor D. Kaganovich; Edward Startsev; S. Klasky; Ronald C. Davidson

    2002-04-09

    Neutralization of the ion beam charge and current is an important scientific issue for many practical applications. The process of ion beam charge and current neutralization is complex because the excitation of nonlinear plasma waves may occur. Computer simulation images of plasma neutralization of the ion beam pulse are presented.

  6. The delusions of net neutrality Andrew Odlyzko

    E-print Network

    Odlyzko, Andrew M.

    The delusions of net neutrality Andrew Odlyzko School of Mathematics, University of Minnesota Abstract. Service providers argue that if net neutrality is not enforced, they will have sufficient evolution. But what if they do get their wish, net neutrality is consigned to the dustbin, and they do build

  7. The Net Neutrality Debate: The Basics

    ERIC Educational Resources Information Center

    Greenfield, Rich

    2006-01-01

    Rich Greenfield examines the basics of today's net neutrality debate that is likely to be an ongoing issue for society. Greenfield states the problems inherent in the definition of "net neutrality" used by Common Cause: "Network neutrality is the principle that Internet users should be able to access any web content they choose and use any…

  8. The delusions of net neutrality Andrew Odlyzko

    E-print Network

    Odlyzko, Andrew M.

    The delusions of net neutrality Andrew Odlyzko School of Mathematics, University of Minnesota Abstract. Service providers argue that if net neutrality is not enforced, they will have su evolution. But what if they do get their wish, net neutrality is consigned to the dustbin, and they do build

  9. Reconciling niche and neutrality: the continuum hypothesis

    Microsoft Academic Search

    Dominique Gravel; Charles D. Canham; Marilou Beaudet; Christian Messier

    2006-01-01

    In this study, we ask if instead of being fundamentally opposed, niche and neutral theories could simply be located at the extremes of a continuum. First, we present a model of recruitment probabilities that combines both niche and neutral processes. From this model, we predict and test whether the relative importance of niche vs. neutral processes in controlling community dynamics

  10. Neutral beamline with improved ion energy recovery

    DOEpatents

    Kim, Jinchoon (San Diego, CA)

    1984-01-01

    A neutral beamline employing direct energy recovery of unneutralized residual ions is provided which enhances the energy recovery of the full energy ion component of the beam exiting the neutralizer cell, and thus improves the overall neutral beamline efficiency. The unneutralized full energy ions exiting the neutralizer are deflected from the beam path and the electrons in the cell are blocked by a magnetic field applied transverse to the beam direction in the neutral izer exit region. The ions which are generated at essentially ground potential and accelerated through the neutralizer cell by a negative acceleration voltage are collected at ground potential. A neutralizer cell exit end region is provided which allows the magnetic and electric fields acting on the exiting ions to be loosely coupled. As a result, the fractional energy ions exiting the cell are reflected onto and collected at an interior wall of the neutralizer formed by the modified end geometry, and thus do not detract from the energy recovery efficiency of full energy ions exiting the cell. Electrons within the neutralizer are prevented from exiting the neutralizer end opening by the action of crossed fields drift (ExB) and are terminated to a collector collar around the downstream opening of the neutralizer. The correct combination of the extended neutralizer end structure and the magnet region is designed so as to maximize the exit of full energy ions and to contain the fractional energy ions.

  11. Neutral hydrogen profiles of cluster galaxies

    NASA Technical Reports Server (NTRS)

    Mould, Jeremy; Martin, Sarah; Bothun, Greg; Huchra, John; Schommer, Bob

    1995-01-01

    Neutral hydrogen profiles of 67 galaxies in seven nearby clusters have been obtained with the Arecibo telescope. The neutral hydrogen masses of these galaxies range from 2 x 10(exp 8) to 2 x 10(exp 10) M. There is no evidence for significant neutral hydrogen deficiency in any of these clusters.

  12. Electron Emission Mechanism of Microwave Discharge Neutralizer

    Microsoft Academic Search

    Noriyoshi Onodera; Haruki Takegahara; Kazutaka Nishiyama; Ikko Funaki; Hitoshi Kuninaka

    2002-01-01

    Institute of Space and Astronautical Science has developed a cathodeless microwave discharge neutralizer for the microwave ion engine system. In order to clarify the electron emission mechanism of the microwave neutralizer, electron current characteristics as well as plasma parameters inside the neuralizer were measured. The electron current was greatly influenced by the material of the neutralizer orifice. Among several materials

  13. Lymph Node Co-Infection of Mycobacterium Avium Complex and Cytomegalovirus in an Acquired Immunodeficiency Syndrome Patient

    PubMed Central

    Hedjazi, Arya; Hosseini, Marzieh; Hoseinzadeh, Amin

    2013-01-01

    Acquired immunodeficiency syndrome patients are known to have an increased tendency for developing opportunistic infections. However, there are no reports of simultaneous lymph node involvement of cytomegalovirus and Mycobacterium avium complex in a human immunodeficiency virus-positive patient. We report a 31-year-old man who presented with acute abdominal pain and tenderness and weight loss. He died a few hours after admission. Autopsy studies showed coinfection of cytomegalovirus, Mycobacterium avium complex and human immunodeficiency virus. Our case emphasizes the need to be careful in evaluating opportunistic infections in severely immunodepressed acquired immunodeficiency syndrome patients. This case report is the first manifestation of acquired immunodeficiency syndrome in this patient. PMID:24470953

  14. Network neutrality, search neutrality, and the neverending conflict between e#ciency and fairness

    E-print Network

    Odlyzko, Andrew M.

    on society mean that no fixed set of rules can work indefinitely. Should net neutrality or some similar set of speculation. On the other hand, net neutrality and its close relatives, such as common carriage neutral communication infrastructure can be viable. And if it is not, just how far from net neutrality

  15. Global Structure of HIV-1 Neutralizing Antibody IgG1 b12 is Asymmetric

    SciTech Connect

    Ashish, F.; Solanki, A; Boone, C; Krueger, J

    2010-01-01

    Human antibody IgG1 b12 is one of the four antibodies known to neutralize a broad range of human immunodeficiency virus-1. The crystal structure of this antibody displayed an asymmetric disposition of the Fab arms relative to its Fc portion. Comparison of structures solved for other IgG1 antibodies led to a notion that crystal packing forces entrapped a 'snap-shot' of different conformations accessible to this antibody. To elucidate global structure of this unique antibody, we acquired small-angle X-ray scattering data from its dilute solution. Data analysis indicated that b12 adopts a bilobal globular structure in solution with a radius of gyration and a maximum linear dimension of {approx}54 and {approx}180 {angstrom}, respectively. Extreme similarity between its solution and crystal structure concludes that non-flexible, asymmetric shape is an inherent property of this rare antibody.

  16. UCLA1, a synthetic derivative of a gp120 RNA aptamer, inhibits entry of human immunodeficiency virus type 1 subtype C.

    PubMed

    Mufhandu, Hazel T; Gray, Elin S; Madiga, Maphuti C; Tumba, Nancy; Alexandre, Kabamba B; Khoza, Thandeka; Wibmer, Constantinos Kurt; Moore, Penny L; Morris, Lynn; Khati, Makobetsa

    2012-05-01

    Entry of human immunodeficiency virus type 1 (HIV-1) into cells is mediated by the virion surface envelope (Env) glycoproteins, making it a desirable target for antiretroviral entry inhibitors. We previously isolated a family of gp120 binding RNA aptamers and showed that they neutralized the infectivity of HIV-1. In this study, we assessed the activity of a shortened synthetic derivative of the B40 aptamer, called UCLA1, against a large panel of HIV-1 subtype C viruses. UCLA1 tightly bound to a consensus HIV-1 subtype C gp120 and neutralized isolates of the same subtype with 50% inhibitory concentrations (IC(50)s) in the nanomolar range. The aptamer had little toxicity in tests with cell lines and primary cells. Furthermore, it exhibited high therapeutic indices, suggesting that it may be effective at very low doses. Mapping of UCLA1 binding sites on gp120 revealed eight amino acid residues that modulated neutralization resistance. This included residues within the coreceptor binding site, at the base of the V3 loop, and in the bridging sheet within the conserved V1/V2 stem-loop of gp120. The aptamer was also shown to have synergistic effects with T20, a gp41 fusion inhibitor, and IgG1b12 (b12), an anti-CD4 binding site monoclonal antibody. These results suggest that UCLA1 may be suitable for development as a potent HIV-1 entry inhibitor. PMID:22379083

  17. Replicating Rather than Nonreplicating Adenovirus-Human Immunodeficiency Virus Recombinant Vaccines Are Better at Eliciting Potent Cellular Immunity and Priming High-Titer Antibodies

    PubMed Central

    Peng, Bo; Wang, Liqun Rejean; Gómez-Román, Victor Raúl; Davis-Warren, Alberta; Montefiori, David C.; Kalyanaraman, V. S.; Venzon, David; Zhao, Jun; Kan, Elaine; Rowell, Thomas J.; Murthy, Krishna K.; Srivastava, Indresh; Barnett, Susan W.; Robert-Guroff, Marjorie

    2005-01-01

    A major challenge in combating the human immunodeficiency virus (HIV) epidemic is the development of vaccines capable of inducing potent, persistent cellular immunity and broadly reactive neutralizing antibody responses to HIV type 1 (HIV-1). We report here the results of a preclinical trial using the chimpanzee model to investigate a combination vaccine strategy involving sequential priming immunizations with different serotypes of adenovirus (Ad)/HIV-1MNenv/rev recombinants and boosting with an HIV envelope subunit protein, oligomeric HIVSF162 gp140?V2. The immunogenicities of replicating and nonreplicating Ad/HIV-1MNenv/rev recombinants were compared. Replicating Ad/HIV recombinants were better at eliciting HIV-specific cellular immune responses and better at priming humoral immunity against HIV than nonreplicating Ad-HIV recombinants carrying the same gene insert. Enhanced cellular immunity was manifested by a greater frequency of HIV envelope-specific gamma interferon-secreting peripheral blood lymphocytes and better priming of T-cell proliferative responses. Enhanced humoral immunity was seen in higher anti-envelope binding and neutralizing antibody titers and better induction of antibody-dependent cellular cytotoxicity. More animals primed with replicating Ad recombinants mounted neutralizing antibodies against heterologous R5 viruses after one or two booster immunizations with the mismatched oligomeric HIV-1SF162 gp140?V2 protein. These results support continued development of the replicating Ad-HIV recombinant vaccine approach and suggest that the use of replicating vectors for other vaccines may prove fruitful. PMID:16051813

  18. Mucosal Priming with a Replicating-Vaccinia Virus-Based Vaccine Elicits Protective Immunity to Simian Immunodeficiency Virus Challenge in Rhesus Monkeys

    PubMed Central

    Sun, Caijun; Tang, Xian; Zhang, Yinfeng; Feng, Liqiang; Du, Yanhua; Xiao, Lijun; Liu, Li; Zhu, Weijun; Chen, Ling

    2013-01-01

    Mucosal surfaces are not targeted by most human immunodeficiency virus type 1 (HIV-1) vaccines, despite being major routes for HIV-1 transmission. Here we report a novel vaccination regimen consisting of a mucosal prime with a modified replicating vaccinia virus Tiantan strain (MVTTSIVgpe) and an intramuscular boost with a nonreplicating adenovirus strain (Ad5SIVgpe). This regimen elicited robust cellular immune responses with enhanced magnitudes, sustainability, and polyfunctionality, as well as higher titers of neutralizing antibodies against the simian immunodeficiency virus SIVmac1A11 in rhesus monkeys. The reductions in peak and set-point viral loads were significant in most animals, with one other animal being protected fully from high-dose intrarectal inoculation of SIVmac239. Furthermore, the animals vaccinated with this regimen were healthy, while ?75% of control animals developed simian AIDS. The protective effects correlated with the vaccine-elicited SIV-specific CD8+ T cell responses against Gag and Pol. Our study provides a novel strategy for developing an HIV-1 vaccine by using the combination of a replicating vector and mucosal priming. PMID:23487457

  19. Diagnosis and Treatment of Gastrointestinal Disorders in Patients With Primary Immunodeficiency

    PubMed Central

    AGARWAL, SHRADHA; MAYER, LLOYD

    2013-01-01

    Gastrointestinal disorders such as chronic or acute diarrhea, malabsorption, abdominal pain, and inflammatory bowel diseases can indicate immune deficiency. The gastrointestinal tract is the largest lymphoid organ in the body, so it is not surprising that intestinal diseases are common among immunodeficient patients. Gastroenterologists therefore must be able to diagnose and treat patients with primary immunodeficiency. Immune-related gastrointestinal diseases can be classified as those that develop primarily via autoimmunity, infection, an inflammatory response, or malignancy. Immunodeficient and immunocompetent patients with gastrointestinal diseases present with similar symptoms. However, intestinal biopsy specimens from immunodeficient patients often have distinct histologic features, and these patients often fail to respond to conventional therapies. Therefore, early recognition of symptoms and referral to an immunologist for a basic immune evaluation is required to select appropriate treatments. Therapies for primary immunodeficiency comprise immunoglobulin replacement, antibiotics, and, in severe cases, bone marrow transplantation. Treatment of immunodeficient patients with concomitant gastrointestinal disease can be challenging, and therapy with immunomodulators often is required for severe disease. This review aims to guide gastroenterologists in the diagnosis and treatment of patients with primary immunodeficiency. PMID:23501398

  20. Diagnosis and treatment of gastrointestinal disorders in patients with primary immunodeficiency.

    PubMed

    Agarwal, Shradha; Mayer, Lloyd

    2013-09-01

    Gastrointestinal disorders such as chronic or acute diarrhea, malabsorption, abdominal pain, and inflammatory bowel diseases can indicate immune deficiency. The gastrointestinal tract is the largest lymphoid organ in the body, so it is not surprising that intestinal diseases are common among immunodeficient patients. Gastroenterologists therefore must be able to diagnose and treat patients with primary immunodeficiency. Immune-related gastrointestinal diseases can be classified as those that develop primarily via autoimmunity, infection, an inflammatory response, or malignancy. Immunodeficient and immunocompetent patients with gastrointestinal diseases present with similar symptoms. However, intestinal biopsy specimens from immunodeficient patients often have distinct histologic features, and these patients often fail to respond to conventional therapies. Therefore, early recognition of symptoms and referral to an immunologist for a basic immune evaluation is required to select appropriate treatments. Therapies for primary immunodeficiency comprise immunoglobulin replacement, antibiotics, and, in severe cases, bone marrow transplantation. Treatment of immunodeficient patients with concomitant gastrointestinal disease can be challenging, and therapy with immunomodulators often is required for severe disease. This review aims to guide gastroenterologists in the diagnosis and treatment of patients with primary immunodeficiency. PMID:23501398

  1. Neutralization of multi-MeV light negative ions by plasma neutralizers

    SciTech Connect

    Hershcovitch, A.I.; Johnson, B.M.; Kovarik, V.J.; Meron, M.; Jones, K.W.; Prelec, K.; Grisham, L.R.

    1984-11-01

    A hollow cathode discharge fed plasma neutralizer has been built and was used to neutralize 3-MeV Li/sup -/, C/sup -/, and Si/sup -/ ions. Initial results indicate that the performance of an unoptimized plasma neutralizer is better than gas stripping. Since hollow cathodes produce plasma targets with high efficiency, this type of plasma neutralizer can improve the overall efficiency of a neutral beam line.

  2. [Tuberculous orchiepididymitis as clinical onset of human immunodeficiency virus (HIV) infection].

    PubMed

    Anglada Curado, F J; Gómez Bermudo, J; Carmona Campos, E; Blanco Espinosa, A; Prieto Castro, R; Regueiro López, J C; Requena Tapia, M J

    1999-01-01

    The emergence of acquired immunodeficiency syndrome has changed the natural history of tuberculosis which has now become the second most common infection associated to human immunodeficiency virus infection. It is only rarely that a tuberculous infection has an urogenital location, and extrapulmonary locations are generally related to severe immunosuppression. This paper presents one case of tuberculous orchitis that presented as the clinical onset of acquired immunodeficiency syndrome. Discussion of the clinical evolution and the therapeutic approach that consisted in orchiectomy associated to treatment with tuberculostatics. PMID:10670136

  3. Three difficult cases: the challenge of autoimmunity, immunodeficiency and recurrent infections in patients with Good syndrome.

    PubMed

    Arnold, S J; Hodgson, T; Misbah, S A; Patel, S Y; Cooper, S M; Venning, V A

    2015-03-01

    Good syndrome (GS) is a rare, adult-acquired primary combined immunodeficiency syndrome arising in the context of previous or current thymoma. Patients with GS frequently develop recurrent sinopulmonary infections and are also at high risk of autoimmune manifestations, including skin conditions such as lichen planus. We report three middle-aged patients with GS complicated by multiple autoimmune and infectious manifestations. The combination of immunodeficiency, autoimmunity and recurrent infections seen in patients with GS continues to present a management challenge, particularly in patients with oral mucosal disease and recurrent candidiasis. Clinicians should be prompted to investigate an underlying immunodeficiency in patients with multiple autoimmune conditions and recurrent sinopulmonary infections. PMID:25059810

  4. Space station neutral external environment

    NASA Technical Reports Server (NTRS)

    Ehlers, H.; Leger, L.

    1988-01-01

    Molecular contamination levels arising from the external induced neutral environment of the Space Station (Phase 1 configuration) were calculated using the MOLFLUX model. Predicted molecular column densities and deposition rates generally meet the Space Station contamination requirements. In the doubtful cases of deposition due to materials outgassing, proper material selection, generally excluding organic products exposed to the external environment, must be considered to meet contamination requirements. It is important that the Space Station configuration, once defined, is not significantly modified to avoid introducing new unacceptable contamination sources.

  5. Neutral gas dynamics in fireballs

    SciTech Connect

    Stenzel, R. L. [Department of Physics and Astronomy, University of California, Los Angeles, California 90095-1547 (United States); Ionita, C.; Schrittwieser, R. [University of Innsbruck, Department for Ion Physics and Applied Physics, A-6020 Innsbruck (Austria)

    2011-06-01

    Fireballs are local discharge phenomena on positively biased electrodes in partially ionized plasmas. Electrons, energized at a double layer, heat neutral gas which expands. The gas pressure exceeds the plasma pressure, hence becomes important to the stability and transport in fireballs. The flow of gas moves the electrode and sensors similar to a mica pendulum. Flow speed and directions are measured. A fireball gun has been developed to partially collimate the flow of hot gas and heat objects in its path. New applications of fireballs are suggested.

  6. High Cell-Free Virus Load and Robust Autologous Humoral Immune Responses in Breast Milk of Simian Immunodeficiency Virus-Infected African Green Monkeys ?

    PubMed Central

    Wilks, Andrew B.; Perry, James R.; Ehlinger, Elizabeth P.; Zahn, Roland C.; White, Robert; Gauduin, Marie-Claire; Carville, Angela; Seaman, Michael S.; Schmitz, Joern E.; Permar, Sallie R.

    2011-01-01

    The design of immunologic interventions to prevent postnatal transmission of human immunodeficiency virus (HIV) will require identification of protective immune responses in this setting. Simian immunodeficiency virus (SIV)-infected rhesus monkeys (RMs), a species that develops an AIDS-like illness following experimental infection, transmit the virus at a high rate during breastfeeding. In contrast, postnatal transmission of SIV occurs rarely or not at all in natural, asymptomatic primate hosts of SIV. These contrasting transmission patterns provide a unique opportunity to study mechanisms that evolved to protect suckling infants from SIV infection. We compared the virologic and immunologic properties of milk of SIV-infected and uninfected natural hosts of SIV, African green monkeys (AGMs), to that of RMs. Interestingly, despite a low number of milk CD4+ T lymphocytes in uninfected AGMs, milk virus RNA load in SIV-infected AGMs was comparable to that of SIV-infected RMs and that in AGM plasma. This observation is in contrast to the relatively low virus load in milk compared to that in plasma of SIV-infected RMs and HIV-infected women. Milk of SIV-infected AGMs also displayed robust virus-specific cellular immune responses. Importantly, an autologous challenge virus-specific neutralization response was detected in milk of five of six SIV-infected AGMs that was comparable in magnitude to that in plasma. In contrast, autologous challenge virus neutralization was not detectable in milk of SIV-infected RMs. The autologous virus-specific adaptive immune responses in breast milk of AGMs may contribute to impedance of virus transmission in the infant oral/gastrointestinal tract and the rarity of postnatal virus transmission in natural hosts of SIV. PMID:21734053

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

    PubMed Central

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

    2014-01-01

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

  8. Newborn screening for severe combined immunodeficiency: an opportunity for intervention.

    PubMed

    Buchbinder, D; Puthenveetil, G; Soni, A; Hsieh, L; Nugent, D; Church, J A

    2013-08-01

    Severe combined immunodeficiency (SCID) is a potentially fatal disorder characterized by defective T- and B-lymphocyte function. We describe a 34-week female twin who had developed feeding intolerance, perioral cyanosis, abdominal distension and neutropenia at 1 month of age. Despite several evaluations including an 'inconclusive' newborn screening result for SCID, the presence of profound lymphopenia was unappreciated. Eventually a diagnosis of SCID in association with adenosine deaminase deficiency was made. This case serves to emphasize the importance of newborn screening for SCID in the context of careful evaluation of clinical and laboratory findings that may be overlooked and result in a delay in the diagnosis of a potentially life-threatening condition. PMID:23897312

  9. Human immunodeficiency virus infection in the healthcare worker.

    PubMed

    Bradley-Springer, L

    1993-01-01

    The 1990 report of transmission of human immunodeficiency virus in a Florida dental office sparked a massive public fear reaction. In response, the Centers for Disease Control and Prevention produced six recommendations that provide few benefits, at what may prove to be an exorbitant cost. The author reviews those recommendations in light of the legal and ethical considerations of informed consent, significant risk, fear, confidentiality, privacy, and right to work. An alternative approach is recommended which would use human, economic, and leadership resources. This approach focuses attention on improved health care through research, product development, education, and enforcement of safety measures, and recognition and control of high-risk situations through education and government leadership. PMID:8386950

  10. Renal transplantation in human immunodeficiency virus (HIV)-positive children.

    PubMed

    McCulloch, Mignon I; Kala, Udai K

    2015-04-01

    Renal transplantation is being performed in adult human immunodeficiency virus (HIV)-positive patients and increasingly in paediatric patients as well. A multidisciplinary team involving an infectious disease professional is required to assist with HIV viral-load monitoring and in choosing the most appropriate highly active antiretroviral therapy (HAART). Drug interactions complicate immunosuppressant therapy and require careful management. The acute rejection rates appear to be similar in adults to those in noninfective transplant recipients. Induction with basiliximab and calcineurin-based immunosuppression appears to be safe and effective in these recipients. Prophylaxis is advised for a variety of infections and may need life-long administration, especially in children. Organ shortage remains a significant problem, and kidneys from deceased HIV-positive donors have been used successfully in a small study population. Overall, with careful planning and close follow-up, successful renal transplantation for paediatric HIV-infected recipients is possible. PMID:24691821

  11. Endocrinologic and metabolic manifestations of the acquired immunodeficiency syndrome.

    PubMed

    Poretsky, L; Maran, A; Zumoff, B

    1990-09-01

    The endocrine abnormalities associated with acquired immunodeficiency syndrome (AIDS) are reviewed. These include adrenal insufficiency, hyporeninemic hypoaldosteronism, panhypopituitarism, hypogonadism, and alterations in thyroid function tests. AIDS-related infections or neoplasms may lead to hypercalcemia, whereas malabsorption may cause hypocalcemia. The possibility that AIDS-associated cachexia and hypertriglyceridemia may be caused by cachectin (tumor necrosis factor) is discussed, along with possible therapy for cachexia with megestrol acetate. Ketoconazole, sulfonamides, and pentamidine have specific, potentially deleterious metabolic effects when used in AIDS patients. Because treatment of endocrinological abnormalities of AIDS is often effective, improved diagnosis and appropriate therapy of these abnormalities will result in improved quality of life and, possibly, longer survival of patients with AIDS. PMID:2247101

  12. Primary Immunodeficiencies: “New” Disease in an Old Country

    PubMed Central

    Lee, Pamela P W; Lau, Yu-Lung

    2009-01-01

    Primary immunodeficiency disorders (PIDs) are rare inborn errors of the immune system. Patients with PIDs are unique models that exemplify the functional and phenotypic consequences of various immune defects underlying infections, autoimmunity, lymphoproliferation, allergy and cancer. Over 150 PID syndromes were characterized in the past 60 years, with an ever growing list of new entities being discovered. Because of their rarity, multi-center collaboration for pooled data analysis and molecular studies is important to gain meaningful insights into the phenotypic and genetic diversities of PIDs. In this article, we summarize our research findings on PIDs in Chinese population in the past 20 years. Close collaboration among various immunology centers, cross-referrals and systematic data analysis constitute the foundation for research on PIDs. Future directions include establishment of a national PID registry, raising awareness of PIDs and securing sufficient resources for patient care and scientific research. PMID:20003815

  13. Nucleotide sequence and genomic organization of feline immunodeficiency virus.

    PubMed Central

    Talbott, R L; Sparger, E E; Lovelace, K M; Fitch, W M; Pedersen, N C; Luciw, P A; Elder, J H

    1989-01-01

    An infectious molecular clone of the Petaluma strain of feline immunodeficiency virus (FIV) was isolated from a recombinant bacteriophage library containing genomic DNA prepared from FIV-infected Crandall feline kidney (CRFK) cells. The integrated provirus has a total length of 9472 base pairs. Three long open reading frames corresponding to GAG, POL, and ENV gene coding frames are evident. In addition, an open reading frame overlaps the 3' end of POL, in the region that encodes viral infectivity factor in the primate viruses. Several short open reading frames are present in the intergenic region between POL and ENV and within ENV, which may serve as exons for production of TAT and REV equivalents in FIV. Alignment of the predicted amino acid sequences of the FIV proteins with those of other lentiviruses indicates that FIV did not arise recently from any other characterized lentivirus. Images PMID:2762293

  14. Il2rg gene-targeted severe combined immunodeficiency pigs.

    PubMed

    Suzuki, Shunichi; Iwamoto, Masaki; Saito, Yoriko; Fuchimoto, Daiichiro; Sembon, Shoichiro; Suzuki, Misae; Mikawa, Satoshi; Hashimoto, Michiko; Aoki, Yuki; Najima, Yuho; Takagi, Shinsuke; Suzuki, Nahoko; Suzuki, Emi; Kubo, Masanori; Mimuro, Jun; Kashiwakura, Yuji; Madoiwa, Seiji; Sakata, Yoichi; Perry, Anthony C F; Ishikawa, Fumihiko; Onishi, Akira

    2012-06-14

    A porcine model of severe combined immunodeficiency (SCID) promises to facilitate human cancer studies, the humanization of tissue for xenotransplantation, and the evaluation of stem cells for clinical therapy, but SCID pigs have not been described. We report here the generation and preliminary evaluation of a porcine SCID model. Fibroblasts containing a targeted disruption of the X-linked interleukin-2 receptor gamma chain gene, Il2rg, were used as donors to generate cloned pigs by serial nuclear transfer. Germline transmission of the Il2rg deletion produced healthy Il2rg(+/-) females, while Il2rg(-/Y) males were athymic and exhibited markedly impaired immunoglobulin and T and NK cell production, robustly recapitulating human SCID. Following allogeneic bone marrow transplantation, donor cells stably integrated in Il2rg(-/Y) heterozygotes and reconstituted the Il2rg(-/Y) lymphoid lineage. The SCID pigs described here represent a step toward the comprehensive evaluation of preclinical cellular regenerative strategies. PMID:22704516

  15. Glanzmann thrombasthenia associated with human immunodeficiency virus-positive patient.

    PubMed

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

    2014-04-01

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

  16. In vitro assembly of the feline immunodeficiency virus Gag polyprotein.

    PubMed

    Affranchino, José L; González, Silvia A

    2010-06-01

    The retroviral Gag protein is the only viral product that is necessary for the assembly of virions in mammalian cells. We have established an in vitro assembly system to study the assembly properties of purified feline immunodeficiency virus (FIV) Gag protein expressed in bacteria. Under fully defined conditions, the FIV Gag protein assembles into spherical particles of 33 nm in diameter which are morphologically similar to authentic immature particles, albeit smaller than virions. The in vitro assembly of FIV Gag into particles was found to be resistant to the addition of Triton X-100 and required the presence of RNA. Notably, we found that an amino acid substitution in the nucleocapsid domain of Gag that impairs RNA binding and blocks virion production in vivo, also abrogates Gag assembly in vitro. The development of an in vitro assembly system for FIV Gag protein will facilitate the study of the mechanisms by which this protein assembles into immature particles. PMID:20347892

  17. Pyoderma gangrenosum in a patient with common variable primary immunodeficiency

    PubMed Central

    Brzezi?ska-Wcis?o, Ligia

    2013-01-01

    Pyoderma gangrenosum is a rare inflammatory skin condition that is associated with systemic inflammatory diseases. It is characterised by the presence of well-secluded, painful ulcerations, often located on the lower limbs. Similarly as in the case of acne inversa, patients’ markers of the inflammatory process are elevated; including OB, C-reactive protein and leukocytosis. The aetiology takes into account an over-reactive inflammatory response to various factors (presence of the so-called pathergy symptom). Common variable primary immunodeficiency (CVID) is a disease that is rather often recognized and affects about 1/10,000-100,000 individuals. It is a heterogeneous group of disorders of combined B-and T-cell dysfunction. The case is described of a 22-year-old man with pyoderma gangrenosum that coexisted with CVID. PMID:24278072

  18. Circularization of human immunodeficiency virus type 1 DNA in vitro.

    PubMed Central

    Farnet, C M; Haseltine, W A

    1991-01-01

    Linear viral DNA present in cytoplasmic extracts of cells newly infected with human immunodeficiency virus type 1 can be induced to form 1-LTR and 2-LTR circles by incubation of the extracts in the presence of added nucleoside triphosphates. No circular DNA forms are detected when extracts are incubated in the absence of added nucleoside triphosphates. Restriction enzyme analysis and polymerase chain reaction analysis with selected primers, as well as DNA sequence analysis of the polymerase chain reaction products, show that most of the 2-LTR circles are the result of autointegration reactions, while 1-LTR circles result from recombination between the long terminal repeats on the linear viral DNA. In addition, a small amount of simple 2-LTR circles, formed by end-to-end joining of the linear viral DNA, is formed in vitro. Integration of the linear viral DNA into heterologous DNA competes effectively with the formation of 2-LTR circles by autointegration. However, concentrations of target DNA which completely block autointegration have no effect on the formation of 1-LTR circles or simple 2-LTR circles. Factors present in extracts of uninfected cells can mediate the formation of 1-LTR circles and simple 2-LTR circles from purified deproteinated linear viral DNA, indicating that viral proteins are not necessary for the formation of these two types of circular viral DNA. These experiments demonstrate that all the transformations of linear viral DNA which occur in the nuclei of cells infected with human immunodeficiency virus type 1 can be reproduced in vitro. Images PMID:1834863

  19. TRIM5? Modulates Immunodeficiency Virus Control in Rhesus Monkeys

    PubMed Central

    Lim, So-Yon; Rogers, Thomas; Chan, Tiffany; Whitney, James B.; Kim, Jonghwa; Sodroski, Joseph; Letvin, Norman L.

    2010-01-01

    The cytoplasmic TRIM5? proteins of certain mammalian lineages efficiently recognize the incoming capsids of particular retroviruses and potently restrict infection in a species-specific manner. Successful retroviruses have evolved capsids that are less efficiently recognized by the TRIM5? proteins of the natural hosts. To address whether TRIM5? contributes to the outcome of retroviral infection in a susceptible host species, we investigated the impact of TRIM5 polymorphisms in rhesus monkeys on the course of a simian immunodeficiency virus (SIV) infection. Full-length TRIM5? cDNAs were derived from each of 79 outbred monkeys and sequenced. Associations were explored between the expression of particular TRIM5 alleles and both the permissiveness of cells to SIV infection in vitro and clinical sequelae of SIV infection in vivo. Natural variation in the TRIM5? B30.2(SPRY) domain influenced the efficiency of SIVmac capsid binding and the in vitro susceptibility of cells from the monkeys to SIVmac infection. We also show the importance in vivo of the interaction of SIVmac with different allelic forms of TRIM5, demonstrating that particular alleles are associated with as much as 1.3 median log difference in set-point viral loads in SIVmac-infected rhesus monkeys. Moreover, these allelic forms of TRIM5 were associated with the extent of loss of central memory (CM) CD4+ T cells and the rate of progression to AIDS in the infected monkeys. These findings demonstrate a central role for TRIM5? in limiting the replication of an immunodeficiency virus infection in a primate host. PMID:20107597

  20. Transplantation Outcomes for Severe Combined Immunodeficiency, 2000–2009

    PubMed Central

    Pai, Sung-Yun; Logan, Brent R.; Griffith, Linda M.; Buckley, Rebecca H.; Parrott, Roberta E.; Dvorak, Christopher C.; Kapoor, Neena; Hanson, Imelda C.; Filipovich, Alexandra H.; Jyonouchi, Soma; Sullivan, Kathleen E.; Small, Trudy N.; Burroughs, Lauri; Skoda-Smith, Suzanne; Haight, Ann E.; Grizzle, Audrey; Pulsipher, Michael A.; Chan, Ka Wah; Fuleihan, Ramsay L.; Haddad, Elie; Loechelt, Brett; Aquino, Victor M.; Gillio, Alfred; Davis, Jeffrey; Knutsen, Alan; Smith, Angela R.; Moore, Theodore B.; Schroeder, Marlis L.; Goldman, Frederick D.; Connelly, James A.; Porteus, Matthew H.; Xiang, Qun; Shearer, William T.; Fleisher, Thomas A.; Kohn, Donald B.; Puck, Jennifer M.; Notarangelo, Luigi D.; Cowan, Morton J.; O’Reilly, Richard J.

    2014-01-01

    BACKGROUND The Primary Immune Deficiency Treatment Consortium was formed to analyze the results of hematopoietic-cell transplantation in children with severe combined immunodeficiency (SCID) and other primary immunodeficiencies. Factors associated with a good transplantation outcome need to be identified in order to design safer and more effective curative therapy, particularly for children with SCID diagnosed at birth. METHODS We collected data retrospectively from 240 infants with SCID who had received transplants at 25 centers during a 10-year period (2000 through 2009). RESULTS Survival at 5 years, freedom from immunoglobulin substitution, and CD3+ T-cell and IgA recovery were more likely among recipients of grafts from matched sibling donors than among recipients of grafts from alternative donors. However, the survival rate was high regardless of donor type among infants who received transplants at 3.5 months of age or younger (94%) and among older infants without prior infection (90%) or with infection that had resolved (82%). Among actively infected infants without a matched sibling donor, survival was best among recipients of haploidentical T-cell–depleted transplants in the absence of any pretransplantation conditioning. Among survivors, reduced-intensity or myeloablative pre-transplantation conditioning was associated with an increased likelihood of a CD3+ T-cell count of more than 1000 per cubic millimeter, freedom from immunoglobulin substitution, and IgA recovery but did not significantly affect CD4+ T-cell recovery or recovery of phytohemagglutinin-induced T-cell proliferation. The genetic subtype of SCID affected the quality of CD3+ T-cell recovery but not survival. CONCLUSIONS Transplants from donors other than matched siblings were associated with excellent survival among infants with SCID identified before the onset of infection. All available graft sources are expected to lead to excellent survival among asymptomatic infants. (Funded by the National Institute of Allergy and Infectious Diseases and others.) PMID:25075835

  1. 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

  2. Gene therapy for primary immunodeficiencies: current status and future prospects.

    PubMed

    Qasim, Waseem; Gennery, Andrew R

    2014-06-01

    Gene therapy using autologous haematopoietic stem cells offers a valuable treatment option for patients with primary immunodeficiencies who do not have access to an HLA-matched donor, although such treatments have not been without their problems. This review details gene therapy trials for X-linked and adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome (WAS) and chronic granulomatous disease (CGD). X-linked SCID was chosen for gene therapy because of previous 'natural' genetic correction through a reversion event in a single lymphoid precursor, demonstrating limited thymopoiesis and restricted T-lymphocyte receptor repertoire, showing selective advantage of progenitors possessing the wild-type gene. In early studies, patients were treated with long terminal repeats-intact gamma-retroviral vectors, without additional chemotherapy. Early results demonstrated gene-transduced cells, sustained thymopoiesis, and a diverse T-lymphocyte repertoire with normal function. Serious adverse effects were subsequently reported in 5 of 20 patients, with T-lymphocyte leukaemia developing, secondary to the viral vector integrating adjacent to a known oncogene. New trials using self-inactivating gamma-retroviral vectors are progressing. Trials for ADA-SCID using gamma-retroviral vectors have been successful, with no similar serious adverse effects reported; trials using lentiviral vectors are in progress. Patients with WAS and CGD treated with early gamma-retroviral vectors have developed similar lymphoproliferative adverse effects to those seen in X-SCID--current trials are using new-generation vectors. Targeted gene insertion using homologous recombination of corrected gene sequences by cellular DNA repair pathways following targeted DNA breakage will improve efficacy and safety of gene therapy. A number of new techniques are discussed. PMID:24848753

  3. Mapping the encapsidation determinants of feline immunodeficiency virus.

    PubMed

    Kemler, Iris; Barraza, Roman; Poeschla, Eric M

    2002-12-01

    Encapsidation of retroviral RNA involves specific interactions between viral proteins and cis-acting genomic RNA sequences. Human immunodeficiency virus type 1 (HIV-1) RNA encapsidation determinants appear to be more complex and dispersed than those of murine retroviruses. Feline lentiviral (feline immunodeficiency virus [FIV]) encapsidation has not been studied. To gain comparative insight into lentiviral encapsidation and to optimize FIV-based vectors, we used RNase protection assays of cellular and virion RNAs to determine packaging efficiencies of FIV deletion mutants, and we studied replicative phenotypes of mutant viruses. Unlike the case for other mammalian retroviruses, the sequences between the major splice donor (MSD) and the start codon of gag contribute negligibly to FIV encapsidation. Moreover, molecular clones having deletions in this region were replication competent. In contrast, sequences upstream of the MSD were important for encapsidation, and deletion of the U5 element markedly reduced genomic RNA packaging. The contribution of gag sequences to packaging was systematically investigated with subgenomic FIV vectors containing variable portions of the gag open reading frame, with all virion proteins supplied in trans. When no gag sequence was present, packaging was abolished and marker gene transduction was absent. Inclusion of the first 144 nucleotides (nt) of gag increased vector encapsidation to detectable levels, while inclusion of the first 311 nt increased it to nearly wild-type levels and resulted in high-titer FIV vectors. However, the identified proximal gag sequence is necessary but not sufficient, since viral mRNAs that contain all coding regions, with or without as much as 119 nt of adjacent upstream 5' leader, were excluded from encapsidation. The results identify a mechanism whereby FIV can encapsidate its genomic mRNA in preference to subgenomic mRNAs. PMID:12414931

  4. Feline immunodeficiency virus Gag is a nuclear shuttling protein.

    PubMed

    Kemler, Iris; Saenz, Dyana; Poeschla, Eric

    2012-08-01

    Lentiviral genomic RNAs are encapsidated by the viral Gag protein during virion assembly. The intracellular location of the initial Gag-RNA interaction is unknown. We previously observed feline immunodeficiency virus (FIV) Gag accumulating at the nuclear envelope during live-cell imaging, which suggested that trafficking of human immunodeficiency virus type 1 (HIV-1) and FIV Gag may differ. Here we analyzed the nucleocytoplasmic transport properties of both Gag proteins. We discovered that inhibition of the CRM1 nuclear export pathway with leptomycin B causes FIV Gag but not HIV-1 Gag to accumulate in the nucleus. Virtually all FIV Gag rapidly became intranuclear when the CRM1 export pathway was blocked, implying that most if not all FIV Gag normally undergoes nuclear cycling. In FIV-infected feline cells, some intranuclear Gag was detected in the steady state without leptomycin B treatment. When expressed individually, the FIV matrix (MA), capsid (CA), and nucleocapsid-p2 (NC-p2) domains were not capable of mediating leptomycin B-sensitive nuclear export of a fluorescent protein. In contrast, CA-NC-p2 did mediate nuclear export, with MA being dispensable. We conclude that HIV-1 and FIV Gag differ strikingly in a key intracellular trafficking property. FIV Gag is a nuclear shuttling protein that utilizes the CRM1 nuclear export pathway, while HIV-1 Gag is excluded from the nucleus. These findings expand the spectrum of lentiviral Gag behaviors and raise the possibility that FIV genome encapsidation may initiate in the nucleus. PMID:22623802

  5. Detailed Atomic Structure of Neutral and Near-Neutral Systems

    SciTech Connect

    Oliver, Paul; Hibbert, Alan [School of Mathematics and Physics, Queen's University, Belfast BT7 1NN, Northern Ireland (United Kingdom)

    2011-05-11

    This paper highlights the issues which need to be addressed in undertaking accurate calculations of multi-electron atoms and ions, particularly at or near the neutral end of an isoelectronic sequence. We illustrate the processes through two calculations--of transitions in Cl I and Sn II--and discuss the convergence of our results as well as updating previous work. In particular, in the case of Cl I, we propose new identifications of the levels involved in certain transitions which are important in determining the abundance of chlorine in the inter-stellar medium (ISM), while in singly ionised tin, our calculations suggest a re-evaluation of the the abundance of tin in the ISM. We also confirm recent identification of Sn II lines seen in tokamak plasmas.

  6. Regulation of P-glycoprotein by human immunodeficiency virus-1 in primary cultures of human fetal astrocytes.

    PubMed

    Ashraf, Tamima; Ronaldson, Patrick T; Persidsky, Yuri; Bendayan, Reina

    2011-11-01

    P-glycoprotein (P-gp), a drug efflux pump, is known to alter the bioavailability of antiretroviral drugs at several sites, including the brain. We have previously shown that human immunodeficiency virus-1 (HIV-1) glycoprotein 120 (gp120) induces proinflammatory cytokine secretion and decreases P-gp functional expression in rat astrocytes, a cellular reservoir of HIV-1. However, whether P-gp is regulated in a similar way in human astrocytes is unknown. This study investigates the regulation of P-gp in an in vitro model of gp120-triggered human fetal astrocytes (HFAs). In this system, elevated levels of interleukin-6 (IL-6), IL-1?, and tumor necrosis factor-? were detected in culture supernatants. Pretreatment with CCR5 neutralizing antibody attenuated cytokine secretion, suggesting that gp120-CCR5 interaction mediated cytokine production. Treatment with gp120 (R5-tropic) resulted in reduced P-gp expression (64%) and function as determined by increased (1.6-fold) cellular accumulation of [(3) H]digoxin, a P-gp substrate. Exposure to R5 or R5/X4-tropic viral isolates led to a downregulation in P-gp expression (75% or 90%, respectively), and treatment with IL-6 also showed lower P-gp expression (50%). Moreover, IL-6 neutralizing antibody blocked gp120-mediated P-gp downregulation, suggesting that IL-6 is a key modulator of P-gp. Gp120- or IL-6-mediated downregulation of P-gp was attenuated by SN50 (a nuclear factor-?B [NF-?B] inhibitor), suggesting involvement of NF-?B signaling in P-gp regulation. Our results suggest that, similarly to the case with rodent astrocytes, pathophysiological stressors associated with brain HIV-1 infection have a downregulatory effect on P-gp functional expression in human astrocytes, which may ultimately result in altered antiretroviral drug accumulation within brain parenchyma. PMID:21826700

  7. Regulation of P-Glycoprotein by Human Immunodeficiency Virus-1 in Primary Cultures of Human Fetal Astrocytes

    PubMed Central

    Ashraf, Tamima; Ronaldson, Patrick T.; Persidsky, Yuri; Bendayan, Reina

    2014-01-01

    P-glycoprotein (P-gp), a drug efflux pump, is known to alter the bioavailability of antiretroviral drugs at several sites, including the brain. We have previously shown that human immunodeficiency virus-1 (HIV-1) glycoprotein 120 (gp120) induces proinflammatory cytokine secretion and decreases P-gp functional expression in rat astrocytes, a cellular reservoir of HIV-1. However, whether P-gp is regulated in a similar way in human astrocytes is unknown. This study investigates the regulation of P-gp in an in vitro model of gp120-triggered human fetal astrocytes (HFAs). In this system, elevated levels of interleukin-6 (IL-6), IL-1?, and tumor necrosis factor-? were detected in culture supernatants. Pretreatment with CCR5 neutralizing antibody attenuated cytokine secretion, suggesting that gp120-CCR5 interaction mediated cytokine production. Treatment with gp120 (R5-tropic) resulted in reduced P-gp expression (64%) and function as determined by increased (1.6-fold) cellular accumulation of [3H]digoxin, a P-gp substrate. Exposure to R5 or R5/X4-tropic viral isolates led to a down-regulation in P-gp expression (75% or 90%, respectively), and treatment with IL-6 also showed lower P-gp expression (50%). Moreover, IL-6 neutralizing antibody blocked gp120-mediated P-gp downregulation, suggesting that IL-6 is a key modulator of P-gp. Gp120- or IL-6-mediated downregulation of P-gp was attenuated by SN50 (a nuclear factor-?B [NF-?B] inhibitor), suggesting involvement of NF-?B signaling in P-gp regulation. Our results suggest that, similarly to the case with rodent astrocytes, pathophysiological stressors associated with brain HIV-1 infection have a downregulatory effect on P-gp functional expression in human astrocytes, which may ultimately result in altered antiretroviral drug accumulation within brain parenchyma. PMID:21826700

  8. Original Contribution Confidence Intervals for Biomarker-based Human Immunodeficiency Virus

    E-print Network

    Cole, Stephen R.

    Original Contribution Confidence Intervals for Biomarker-based Human Immunodeficiency Virus approaches to confidence interval (CI) estimation for this incidence measure have included 1) ignoring simulation; confidence intervals; HIV; incidence; Monte Carlo method; statistics Abbreviations: AIDS

  9. [Prevalence of anti-Epstein-Barr virus antibodies in children and adolescents with secondary immunodeficiency].

    PubMed

    Bucková, A

    2010-08-01

    Secondary immunodeficiency can be caused by multiple factors. We studied whether there is a relationship between secondary immunodeficiency and Epstein-Barr virus (EBV) infection in children and adolescents. The study group included 845 patients with common variable immunodeficiency aged from 2 to 18 years and 394 age-matched healthy controls. IgM and IgG antibodies against viral capsid antigen (VCA) and IgG antibodies against Epstein-Barr virus nuclear antigen 1 (EBNA-1) were quantitated by an enzyme-linked immunosorbent assay. A statistically significant difference (p = 0.004) in the prevalence of EBV infection was found between the immunodeficient children and controls, both aged 2 to 6 years. The statistically significant difference was confirmed in boys (p = 0.003), but not in girls of this age group. PMID:20925250

  10. Prostatic abscess due to histoplasma capsulatum in the acquired immunodeficiency syndrome.

    PubMed

    Marans, H Y; Mandell, W; Kislak, J W; Starrett, B; Moussouris, H F

    1991-06-01

    We report a case of prostate abscess due to Histoplasma capsulatum in a patient with the acquired immunodeficiency syndrome. The diagnosis and management are discussed, and the literature is reviewed. PMID:2033711

  11. Differential Specificity and Immunogenicity of Adenovirus Type 5 Neutralizing Antibodies Elicited by Natural Infection or Immunization?

    PubMed Central

    Cheng, Cheng; Gall, Jason G. D.; Nason, Martha; King, C. Richter; Koup, Richard A.; Roederer, Mario; McElrath, M. Juliana; Morgan, Cecilia A.; Churchyard, Gavin; Baden, Lindsey R.; Duerr, Ann C.; Keefer, Michael C.; Graham, Barney S.; Nabel, Gary J.

    2010-01-01

    A recent clinical trial of a T-cell-based AIDS vaccine delivered with recombinant adenovirus type 5 (rAd5) vectors showed no efficacy in lowering viral load and was associated with increased risk of human immunodeficiency virus type 1 (HIV-1) infection. Preexisting immunity to Ad5 in humans could therefore affect both immunogenicity and vaccine efficacy. We hypothesized that vaccine-induced immunity is differentially affected, depending on whether subjects were exposed to Ad5 by natural infection or by vaccination. Serum samples from vaccine trial subjects receiving a DNA/rAd5 AIDS vaccine with or without prior immunity to Ad5 were examined for the specificity of their Ad5 neutralizing antibodies and their effect on HIV-1 immune responses. Here, we report that rAd5 neutralizing antibodies were directed to different components of the virion, depending on whether they were elicited by natural infection or vaccination in HIV vaccine trial subjects. Neutralizing antibodies elicited by natural infection were directed largely to the Ad5 fiber, while exposure to rAd5 through vaccination elicited antibodies primarily to capsid proteins other than fiber. Notably, preexisting immunity to Ad5 fiber from natural infection significantly reduced the CD4 and CD8 cell responses to HIV Gag after DNA/rAd5 vaccination. The specificity of Ad5 neutralizing antibodies therefore differs depending on the route of exposure, and natural Ad5 infection compromises Ad5 vaccine-induced immunity to weak immunogens, such as HIV-1 Gag. These results have implications for future AIDS vaccine trials and the design of next-generation gene-based vaccine vectors. PMID:19846512

  12. Toward Effective HIV Vaccination INDUCTION OF BINARY EPITOPE REACTIVE ANTIBODIES WITH BROAD HIV NEUTRALIZING ACTIVITY

    SciTech Connect

    Nishiyama, Yasuhiro; Planque, Stephanie; Mitsuda, Yukie; Nitti, Giovanni; Taguchi, Hiroaki; Jin, Lei; Symersky, Jindrich; Boivin, Stephane; Sienczyk, Marcin; Salas, Maria; Hanson, Carl V.; Paul, Sudhir; (Texas-MED); (Viral Rickettsial)

    2009-11-23

    We describe murine monoclonal antibodies (mAbs) raised by immunization with an electrophilic gp120 analog (E-gp120) expressing the rare ability to neutralize genetically heterologous human immunodeficiency virus (HIV) strains. Unlike gp120, E-gp120 formed covalent oligomers. The reactivity of gp120 and E-gp120 with mAbs to reference neutralizing epitopes was markedly different, indicating their divergent structures. Epitope mapping with synthetic peptides and electrophilic peptide analogs indicated binary recognition of two distinct gp120 regions by anti-E-gp120 mAbs, the 421-433 and 288-306 peptide regions. Univalent Fab and single chain Fv fragments expressed the ability to recognize both peptides. X-ray crystallography of an anti-E-gp120 Fab fragment revealed two neighboring cavities, the typical antigen-binding cavity formed by the complementarity determining regions (CDRs) and another cavity dominated by antibody heavy chain variable (VH) domain framework (FR) residues. Substitution of the FR cavity VH Lys-19 residue by an Ala residue resulted in attenuated binding of the 421-433 region peptide probe. The CDRs and VH FR replacement/silent mutation ratios exceeded the ratio for a random mutation process, suggesting adaptive development of both putative binding sites. All mAbs studied were derived from VH1 family genes, suggesting biased recruitment of the V gene germ line repertoire by E-gp120. The conserved 421-433 region of gp120 is essential for HIV binding to host CD4 receptors. This region is recognized weakly by the FR of antibodies produced without exposure to HIV, but it usually fails to induce adaptive synthesis of neutralizing antibodies. We present models accounting for improved CD4-binding site recognition and broad HIV neutralizing activity of the mAbs, long sought goals in HIV vaccine development.

  13. BEAMS3D Neutral Beam Injection Model

    SciTech Connect

    Lazerson, Samuel

    2014-04-14

    With the advent of applied 3D fi elds in Tokamaks and modern high performance stellarators, a need has arisen to address non-axisymmetric effects on neutral beam heating and fueling. We report on the development of a fully 3D neutral beam injection (NBI) model, BEAMS3D, which addresses this need by coupling 3D equilibria to a guiding center code capable of modeling neutral and charged particle trajectories across the separatrix and into the plasma core. Ionization, neutralization, charge-exchange, viscous velocity reduction, and pitch angle scattering are modeled with the ADAS atomic physics database [1]. Benchmark calculations are presented to validate the collisionless particle orbits, neutral beam injection model, frictional drag, and pitch angle scattering effects. A calculation of neutral beam heating in the NCSX device is performed, highlighting the capability of the code to handle 3D magnetic fields.

  14. Molecular Clock on a Neutral Network

    NASA Astrophysics Data System (ADS)

    Raval, Alpan

    2007-09-01

    The number of fixed mutations accumulated in an evolving population often displays a variance that is significantly larger than the mean (the overdispersed molecular clock). By examining a generic evolutionary process on a neutral network of high-fitness genotypes, we establish a formalism for computing all cumulants of the full probability distribution of accumulated mutations in terms of graph properties of the neutral network, and use the formalism to prove overdispersion of the molecular clock. We further show that significant overdispersion arises naturally in evolution when the neutral network is highly sparse, exhibits large global fluctuations in neutrality, and small local fluctuations in neutrality. The results are also relevant for elucidating aspects of neutral network topology from empirical measurements of the substitution process.

  15. Human immunodeficiency virus/acquired immunodeficiency syndrome knowledge among high school students in K?r?kkale province of Turkey

    PubMed Central

    Ayl?kç?, Bahad?r U?ur; Bamise, Cornelius Tokunbo; Hamidi, Mehmet Mustafa; Turkal, Mustafa; Çolak, Hakan

    2013-01-01

    Background: The purpose of the present study was to assess the existing level of knowledge of high school children about human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and the sources of their information. Materials and Methods: A cross-sectional survey was conducted in two high schools in Kirikkale, Turkey and data were collected by a self-administered questionnaire. Multi-stage sampling technique was used to obtain a representative sample. Results: Four hundred and seventy three participants; 230 males and 243 females were analyzed. Their ages ranged from 15 to 19 years with a mean age of 16.81 ± 1.27. 92.2% of the students claimed to have heard about HIV/AIDS prior to the study with slightly more females than males. Although with some misconceptions, majority of the participants knew that HIV is not transmitted by sharing meals, casual contact, and sleeping in the same room and using the same bathroom. 93.4% identi?ed HIV/AIDS as a life-threatening disease and 27% believe that there is a cure for AIDS. 64% and 22.8% respectively believed that the people can protect themselves by using condoms and by avoiding sexual contact. Internet was preponderantly claimed as the most important source of information about HIV/AIDS. Conclusion: Empirical evidence from this study suggests that the students have a fairly high knowledge of HIV/AIDS. This is not without some misconceptions about the prognosis of the disease. Internet was the major source of HIV/AIDS information. PMID:23633840

  16. Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV.

    PubMed

    Wadford, Debra A; Kauffman, Robert C; Deere, Jesse D; Aoki, Scott T; Stanton, Richard A; Higgins, Joanne; Van Rompay, Koen K A; Villalobos, Andradi; Nettles, James H; Schinazi, Raymond F; Pedersen, Niels C; North, Thomas W

    2014-01-01

    RT-SHIV is a chimera of simian immunodeficiency virus (SIV) containing the reverse transcriptase (RT)-encoding region of human immunodeficiency virus type 1 (HIV-1) within the backbone of SIVmac239. It has been used in a non-human primate model for studies of non-nucleoside RT inhibitors (NNRTI) and highly active antiretroviral therapy (HAART). We and others have identified several mutations that arise in the "foreign" HIV-1 RT of RT-SHIV during in vivo replication. In this study we catalogued amino acid substitutions in the HIV-1 RT and in regions of the SIV backbone with which RT interacts that emerged 30 weeks post-infection from seven RT-SHIV-infected rhesus macaques. The virus set points varied from relatively high virus load, moderate virus load, to undetectable virus load. The G196R substitution in RT was detected from 6 of 7 animals at week 4 post-infection and remained in virus from 4 of 6 animals at week 30. Virus from four high virus load animals showed several common mutations within RT, including L74V or V75L, G196R, L214F, and K275R. The foreign RT from high virus load isolates exhibited as much variation as that of the highly variable envelope surface glycoprotein, and 10-fold higher than that of the native RT of SIVmac239. Isolates from moderate virus load animals showed much less variation in the foreign RT than the high virus load isolates. No variation was found in SIVmac239 genes known to interact with RT. Our results demonstrate substantial adaptation of the foreign HIV-1 RT in RT-SHIV-infected macaques, which most likely reflects selective pressure upon the foreign RT to attain optimal activity within the context of the chimeric RT-SHIV and the rhesus macaque host. PMID:24498008

  17. Human immunodeficiency virus type 1 modified to package Simian immunodeficiency virus Vpx efficiently infects macrophages and dendritic cells.

    PubMed

    Sunseri, Nicole; O'Brien, Meagan; Bhardwaj, Nina; Landau, Nathaniel R

    2011-07-01

    The lentiviral accessory protein Vpx is thought to facilitate the infection of macrophages and dendritic cells by counteracting an unidentified host restriction factor. Although human immunodeficiency virus type 1 (HIV-1) does not encode Vpx, the accessory protein can be provided to monocyte-derived macrophages (MDM) and monocyte-derived dendritic cells (MDDC) in virus-like particles, dramatically enhancing their susceptibility to HIV-1. Vpx and the related accessory protein Vpr are packaged into virions through a virus-specific interaction with the p6 carboxy-terminal domain of Gag. We localized the minimal Vpx packaging motif of simian immunodeficiency virus SIVmac(239) p6 to a 10-amino-acid motif and introduced this sequence into an infectious HIV-1 provirus. The chimeric virus packaged Vpx that was provided in trans and was substantially more infectious on MDDC and MDM than the wild-type virus. We further modified the virus by introducing the Vpx coding sequence in place of nef. The resulting virus produced Vpx and replicated efficiently in MDDC and MDM. The virus also induced a potent type I interferon response in MDDC. In a coculture system, the Vpx-containing HIV-1 was more efficiently transmitted from MDDC to T cells. These findings suggest that in vivo, Vpx may facilitate transmission of the virus from dendritic cells to T cells. In addition, the chimeric virus could be used to design dendritic cell vaccines that induce an enhanced innate immune response. This approach could also be useful in the design of lentiviral vectors that transduce these relatively resistant cells. PMID:21507971

  18. Human immunodeficiency virus (HIV) antigens: structure and serology of multivalent human mucin MUC1-HIV V3 chimeric proteins.

    PubMed Central

    Fontenot, J D; Gatewood, J M; Mariappan, S V; Pau, C P; Parekh, B S; George, J R; Gupta, G

    1995-01-01

    Molecular modeling and two-dimensional NMR techniques enable us to identify structural features in the third variable region (V3) loop of the human immunodeficiency virus (HIV) surface glycoprotein gp120, in particular the principal neutralizing determinant (PND), that remain conserved despite the sequence variation. The conserved structure of the PND is a solvent-accessible protruding motif or a knob, structurally isomorphous with the immunodominant knobs in the tandem repeat protein of human mucin 1 (MUC1) (a tumor antigen for breast, pancreatic, and ovarian cancer). We have replaced the mucin antigenic knobs by the PND knobs of the HIV MN isolate in a set of chimeric human MUC1/HIV V3 antigens. This produced multivalent HIV antigens in which PNDs are located at regular intervals and separated by extended mucin spacers. In this article we show by two-dimensional NMR spectroscopy that the multivalent antigens preserve the PNDs in their native structure. We also demonstrate by ELISA that the antigens correctly present the PNDs for binding to monoclonal antibodies or polyclonal antisera from HIV-infected patients. Images Fig. 2 Fig. 3 PMID:7816840

  19. Human immunodeficiency virus type 1 gp120 stimulates cytomegalovirus replication in monocytes: possible role of endogenous interleukin-8.

    PubMed Central

    Capobianchi, M R; Barresi, C; Borghi, P; Gessani, S; Fantuzzi, L; Ameglio, F; Belardelli, F; Papadia, S; Dianzani, F

    1997-01-01

    Recombinant gp120, but not other human immunodeficiency type 1 (HIV-1) structural proteins, dose-dependently stimulates human cytomegalovirus (HCMV) immediate-early antigen (IEA) expression and infectious virus yield in freshly isolated normal monocytes infected with HCMV. Monoclonal antibodies (MAbs) recognizing the gp120 V3 loop, as well as V3 loop octameric multibranched peptides and antibody to galactocerebroside, but not sCD4, abrogate the gp120 stimulation of IEA expression, suggesting that the effect involves V3 loop-galactocerebroside interaction and is not mediated by CD4. Interleukin 8 (IL-8) gene expression is enhanced in monocytes treated with gp120 at the level of both mRNA and released protein. Exogenous IL-8 could replace gp120 in the stimulation of HCMV infection, while a MAb capable of neutralizing IL-8 activity abrogates the gp120-induced HCMV stimulation. These data indicate that HIV-1 glycoprotein induces stimulation of productive infection of monocytes with HCMV and that such stimulation may be mediated by the upregulation of IL-8 gene expression. This is the first evidence that HIV-1 may affect HCMV replication indirectly, via the interaction of gp120 with the monocyte membrane, in the complete absence of retroviral replication, through the stimulation of IL-8 release. Because in HIV-1-infected individuals, HCMV infection is frequently activated and the levels of circulating IL-8 are enhanced, these findings may be pathogenetically relevant. PMID:8995686

  20. Prevention of immunodeficiency virus induced CD4+ T-cell depletion by prior infection with a non-pathogenic virus

    SciTech Connect

    TerWee, Julie A.; Carlson, Jennifer K.; Sprague, Wendy S.; Sondgeroth, Kerry S.; Shropshire, Sarah B.; Troyer, Jennifer L. [Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado (United States); VandeWoude, Sue [Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado (United States)], E-mail: suev@lamar.colostate.edu

    2008-07-20

    Immune dysregulation initiated by a profound loss of CD4+ T-cells is fundamental to HIV-induced pathogenesis. Infection of domestic cats with a non-pathogenic lentivirus prevalent in the puma (puma lentivirus, PLV or FIV{sub PCO}) prevented peripheral blood CD4+ T-cell depletion caused by subsequent virulent FIV infection. Maintenance of this critical population was not associated with a significant decrease in FIV viremia, lending support to the hypothesis that direct viral cytopathic effect is not the primary cause of immunodeficiency. Although this approach was analogous to immunization with a modified live vaccine, correlates of immunity such as a serum-neutralizing antibody or virus-specific T-cell proliferative response were not found in protected animals. Differences in cytokine transcription profile, most notably in interferon gamma, were observed between the protected and unprotected groups. These data provide support for the importance of non-adaptive enhancement of the immune response in the prevention of CD4+ T-cell loss.

  1. Fine definition of the CXCR4-binding region on the V3 loop of feline immunodeficiency virus surface glycoprotein.

    PubMed

    Hu, Qiong-Ying; Fink, Elizabeth; Hong, Yang; Wang, Cathy; Grant, Chris K; Elder, John H

    2010-01-01

    The chemokine receptor CXCR4 is shared by primary and laboratory-adapted strains of feline immunodeficiency virus (FIV) for viral entry. Our previous studies implicated a contiguous nine-amino-acid region of the V3 loop of the FIV envelope surface as important in CXCR4 binding and virus entry. The binding is specific for CXCR4 since it can be inhibited by AMD3100, a selective CXCR4 inhibitor. Additional site-directed mutagenesis was used to further reveal the key residues. Binding studies indicated that basic residues R395, K397, R399 as well as N398 are critical for CXCR4 binding. The effect of other amino acid residues on receptor binding depends on the type of amino acid residue substituted. The binding study results were confirmed on human CXCR4-expressing SupT1 cells and correlated with entry efficiency using a virus entry assay. Amino acid residues critical for CXCR4 are not critical for interactions with the primary binding receptor CD134, which has an equivalent role as CD4 for HIV-1 binding. The ELISA results show that W394 and W400 are crucial for the recognition by neutralizing anti-V3 antibodies. Since certain strains of HIV-1 also use CXCR4 as the entry receptor, the findings make the feline model attractive for development of broad-based entry antagonists and for study of the molecular mechanism of receptor/virus interactions. PMID:20502526

  2. Coreceptor Usage of Sequential Isolates from Cynomolgus Monkeys Experimentally Infected with Simian Immunodeficiency Virus (SIVsm)

    Microsoft Academic Search

    Dalma Vödrös; Rigmor Thorstensson; Gunnel Biberfeld; Dominique Schols; Erik De Clercq; Eva Maria Fenyö

    2001-01-01

    Sequential isolates from eight cynomolgus monkeys experimentally infected with simian immunodeficiency virus (SIVsm, of sooty mangabey origin) were tested for coreceptor use in the human osteosarcoma indicator cell line, GHOST(3), expressing CD4 and one or another of the chemokine receptors CCR3, CCR5, CXCR4, BOB, or the orphan receptor Bonzo. The indicator cell line carries the human immunodeficiency virus type 2

  3. Synergistic neurotoxicity of opioids and human immunodeficiency virus-1 Tat protein in striatal neurons in vitro

    Microsoft Academic Search

    J. A. Gurwell; A. Nath; Q. Sun; J. Zhang; K. M. Martin; Y. Chen; K. F. Hauser

    2001-01-01

    Human immunodeficiency virus (HIV) infection selectively targets the striatum, a region rich in opioid receptor-expressing neural cells, resulting in gliosis and neuronal losses. Opioids can be neuroprotective or can promote neurodegeneration. To determine whether opioids modify the response of neurons to human immunodeficiency virus type 1 (HIV-1) Tat protein-induced neurotoxicity, neural cell cultures from mouse striatum were initially characterized for

  4. Shared Usage of the Chemokine Receptor CXCR4 by the Feline and Human Immunodeficiency Viruses

    Microsoft Academic Search

    BRIAN J. WILLETT; LAURENT PICARD; MARGARET J. HOSIE; JULIE D. TURNER; KAREN ADEMA; PAUL R. CLAPHAM

    1997-01-01

    Feline immunodeficiency virus (FIV) induces a disease state in the domestic cat that is similar to AIDS in human immunodeficiency virus (HIV)-infected individuals. As with HIV, FIV can be divided into primary and cell culture-adapted isolates. Adaptation of FIV to replicate and form syncytia in the Crandell feline kidney (CrFK) cell line is accompanied by an increase in the net

  5. Clinical and epidemiologic aspects of human immunodeficiency virus-1-infected children in Buenos Aires, Argentina

    Microsoft Academic Search

    Aurelia A. Fallo; Wanda Dobrzanski-Nisiewicz; Nora Sordelli; María Alejandra Cattaneo; Gwendolyn Scott; Eduardo L. López

    2002-01-01

    Background: Argentina has the sixth largest number of cumulative pediatric cases of acquired immunodeficiency syndrome (AIDS) in the Americas; therefore, this study was designed to characterize human immunodeficiency virus-1 (HIV-1) infection in children in Buenos Aires, Argentina.Materials and Methods: Medical records of 389 children at risk and infected with HIV-1, an urban population followed by the AIDS Reference Center at

  6. Hyperkalemia in patients infected with the human immunodeficiency virus: Involvement of a systemic mechanism

    Microsoft Academic Search

    Carlos Caramelo; Elena Bello; Elisa Ruiz; Adela Rovira; Rosa M. Gazapo; Jose M. Alcazar; Nieves Martell; Luis M. Ruilope; Santos Casado; Manuel Fernández Guerrero

    1999-01-01

    Hyperkalemia in patients infected with the human immunodeficiency virus: Involvement of a systemic mechanism.BackgroundThe appearance of hyperkalemia has been described in human immunodeficiency virus (HIV)-positive patients treated with drugs with amiloride-like properties. Recent in vitro data suggest that individuals infected with HIV have alterations in transcellular K+ transport.MethodsWith the objective of examining the presence of alterations in transmembrane K+ equilibrium

  7. Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency

    PubMed Central

    Bacalhau, Sílvia; Freitas, Cristina; Valente, Rosalina; Barata, Deolinda; Neves, Conceição; Schäfer, Katrin; Lubatschofski, Annelie; Schulz, Ansgar; Neves, João Farela

    2011-01-01

    In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID) who developed disseminated BCG disease, highlighting the specific strategies adopted. PMID:22110512

  8. Extracellular Vpr Protein Increases Cellular Permissiveness to Human Immunodeficiency Virus Replication and Reactivates Virus from Latency

    Microsoft Academic Search

    DAVID N. LEVY; YOSEF REFAELI; ANDDAVID B. WEINER

    1995-01-01

    The vpr gene product of human immunodeficiency virus (HIV) and simian immunodeficiency virus is a virion-associatedregulatoryproteinthathasbeenshownusingvprmutantvirusestoincreasevirusreplication, particularly in monocytes\\/macrophages. We have previously shown that vpr can directly inhibit cell prolifer- ation and induce cell differentiation, events linked to the control of HIV replication, and also that the replication of a vpr mutant but not that of wild-type HIV type 1

  9. Differences in Feline Immunodeficiency Virus Host Cell Range Correlate with Envelope Fusogenic Properties

    Microsoft Academic Search

    Gianfranco Pancino; Sandrine Castelot; Pierre Sonigo

    1995-01-01

    Feline immunodeficiency virus (FIV) establishes persistent infections in cats inducing an acquired immunodeficiency syndrome. Differences in cell tropism have been observed among isolates of FIV (T. R. Phillips et al., J. Virol. 64, 46054613, 1990). The progeny of the infectious molecular clone of FIV p34TF10 was able to productively infect a feline fibroblast cell line, Crandell feline kidney cell, (CrFK),

  10. Sensitive neutralization test for virus antibody

    Microsoft Academic Search

    H. Sato; P. Albrecht; J. T. Hicks; B. C. Meyer; F. A. Ennis

    1978-01-01

    Summary A sensitive mumps virus plaque neutralization test has been developed based on the potentiation of virus-antibody complexes by heterologous anti-immunoglobulins (AIG). The enhanced neutralization test was approximately 100 times more sensitive than the conventional neutralization test or the hemagglutination-inhibition test. Using AIG against human immunoglobulin G (IgG) or human IgM permitted determination of the relative titers of the two

  11. Laser neutralization of buried munitions

    NASA Astrophysics Data System (ADS)

    Habersat, James D.; Schilling, Bradley W.; Alexander, Joe; McElhaney, Russell; Lehecka, Thomas; Nixon, Matthew D.

    2011-06-01

    This report describes the results of the first phase of a planned two-phase program to develop laser technology for rapid neutralization of buried munitions from a safe standoff distance. The primary objective of this first phase is to demonstrate, via laboratory experiments, the capabilities of a breadboard laser system to "drill" through a minimum depth of 15 cm of earthen materials to defeat a buried mine at a standoff distance greater than 20 m. In the initial phase covered by this report, results of short range laboratory testing by 3 contractors are reported. The planned second phase of this program will consist of procuring a more capable 10 kW SM laser and performing field-testing at longer standoff ranges.

  12. Neutrality and curiosity: elements of technique.

    PubMed

    Nersessian, Edward; Silvan, Matthew

    2007-07-01

    In the past three decades, neutrality has come under increasing criticism. The idea that a psychoanalyst can leave himself out of the therapeutic exchange has come to be seen as either an impossible dream or a myth. We propose that examining neutrality through the lens of curiosity allows for a new appreciation of the ongoing and vital importance of this psychoanalytic attitude. Our hypothesis is that curiosity and neutrality are linked, and that to maintain a neutral stance, the analyst must be able to direct a relatively conflict-free curiosity toward the workings of the analysand's mind as well as his own. PMID:17695334

  13. INVESTIGATION Emergent Neutrality in Adaptive Asexual Evolution

    E-print Network

    Lässig, Michael

    INVESTIGATION Emergent Neutrality in Adaptive Asexual Evolution Stephan Schiffels,*,1 Gergely J the speed of adaptation in large asexual populations (Fisher 1930; Muller 1932; Smith 1971; Felsenstein 1974

  14. Neutral Vlasov kinetic theory of magnetized plasmas

    NASA Astrophysics Data System (ADS)

    Tronci, Cesare; Camporeale, Enrico

    2015-02-01

    The low-frequency limit of Maxwell equations is considered in the Maxwell-Vlasov system. This limit produces a neutral Vlasov system that captures essential features of plasma dynamics, while neglecting radiation effects. Euler-Poincaré reduction theory is used to show that the neutral Vlasov kinetic theory possesses a variational formulation in both Lagrangian and Eulerian coordinates. By construction, the new model recovers all collisionless neutral models employed in plasma simulations. Then, comparisons between the neutral Vlasov system and hybrid kinetic-fluid models are presented in the linear regime.

  15. Operations with tritium neutral beams on TFTR

    SciTech Connect

    Grisham, L.R.; O`Connor, T.; Stevenson, T.N. [and others

    1996-12-31

    In late 1993 the Tokamak Fusion Test Reactor began operating with a deuterium-tritium (DT) fuel mixture instead of the pure deuterium which it had used previously. The major portion of this tritium has initially entered the torus as energetic neutral beam particles. Over 600 deuterium-tritium discharges have now been studied with the aid of more than 2000 tritium ion source shots. The maximum total neutral particle power injected with a mix of deuterium and tritium beams has been 39.6 megawatts, and the maximum injected as tritium neutrals has been 24.3 megawatts. Tritium neutral beam operation has become routine during this time.

  16. Immunization with Wild-Type or CD4-Binding-Defective HIV-1 Env Trimers Reduces Viremia Equivalently following Heterologous Challenge with Simian-Human Immunodeficiency Virus?

    PubMed Central

    Sundling, Christopher; O'Dell, Sijy; Douagi, Iyadh; Forsell, Mattias N.; Mörner, Andreas; Loré, Karin; Mascola, John R.; Wyatt, Richard T.; Karlsson Hedestam, Gunilla B.

    2010-01-01

    We recently reported that rhesus macaques inoculated with CD4-binding-competent and CD4-binding-defective soluble YU2-derived HIV-1 envelope glycoprotein (Env) trimers in adjuvant generate comparable levels of Env-specific binding antibodies (Abs) and T cell responses. We also showed that Abs directed against the Env coreceptor binding site (CoRbs) were elicited only in animals immunized with CD4-binding-competent trimers and not in animals immunized with CD4-binding-defective trimers, indicating that a direct interaction between Env and CD4 occurs in vivo. To investigate both the overall consequences of in vivo Env-CD4 interactions and the elicitation of CoRbs-directed Abs for protection against heterologous simian-human immunodeficiency virus (SHIV) challenge, we exposed rhesus macaques immunized with CD4-binding-competent and CD4-binding-defective trimers to the CCR5-tropic SHIV-SF162P4 challenge virus. Compared to unvaccinated controls, all vaccinated animals displayed improved control of plasma viremia, independent of the presence or absence of CoRbs-directed Abs prior to challenge. Immunization resulted in plasma responses that neutralized the heterologous SHIV challenge stock in vitro, with similar neutralizing Ab titers elicited by the CD4-binding-competent and CD4-binding-defective trimers. The neutralizing responses against both the SHIV-SF162P4 stock and a recombinant virus pseudotyped with a cloned SHIV-SF162P4-derived Env were significantly boosted by the SHIV challenge. Collectively, these results suggest that the capacity of soluble Env trimers to interact with primate CD4 in vivo and to stimulate the production of moderate titers of CoRbs-directed Abs did not influence the magnitude of the neutralizing Ab recall response after viral challenge or the subsequent control of viremia in this heterologous SHIV challenge model. PMID:20610729

  17. Anti-human papillomavirus therapeutics: facts & future.

    PubMed

    Bharti, Alok C; Shukla, Shirish; Mahata, Sutapa; Hedau, Suresh; Das, Bhudev C

    2009-09-01

    Even after 25 years of establishing Human Papillomavirus (HPV) as the causative agent for cervical cancer, effective treatment of HPV infection still unavailable. Comprehensive efforts especially for targeting HPV infection have been made only in recent years. Conventional physical ablation of HPV-induced lesions such as cryo-therapy, photo-therapy, LEEP, laser cone-biopsy and localized radiotherapy are shown to be effective to some extent in treating localized lesions where the removal of diseased tissue is associated with removal of transforming keratinocytes harboring HPV. Apart from currently available prophylactic vaccines which prevent the viral entry and should be given prior to viral exposure, several attempts are being made to develop therapeutic vaccines that could treat prevailing HPV infection. In addition, immunomodulators like interferons and imiquimod that have been shown to elicit cytokine milieu to enhance host immune response against HPV infection. Also, antiviral approaches such as RNA interference (RNAi) nucleotide analogs, antioxidants and herbal derivatives have shown effective therapeutic potential against HPV infection. These leads are being tested in pre-clinical and clinical studies. Present article provides a brief overview of conventional therapies for HPV-associated diseases. Potential of non-ablative anti-HPV treatment modalities that could prove useful for either elimination of HPV in early stages of infection when the virus is not integrated into the host cell genome or suppression of the expression of viral oncogenes that dys-regulate the host cell cycle following transformation is discussed. PMID:19901439

  18. A self-consistent model of plasma and neutrals at Saturn: Neutral cloud morphology

    Microsoft Academic Search

    S. Jurac; J. D. Richardson

    2005-01-01

    We present a model of the plasma and neutral environment that treats plasma and neutrals self-consistently, using Voyager plasma and ultraviolet H observations and Hubble Space Telescope OH measurements as constraints. The neutral distributions are determined with a Monte Carlo model, and the plasma distributions are determined with a diffusive transport model including sources and losses. We find a larger

  19. Human Immunodeficiency Virus and Heparan Sulfate: From Attachment to Entry Inhibition

    PubMed Central

    Connell, Bridgette J.; Lortat-Jacob, Hugues

    2013-01-01

    By targeting cells that provide protection against infection, HIV-1 causes acquired immunodeficiency syndrome. Infection starts when gp120, the viral envelope glycoprotein, binds to CD4 and to a chemokine receptor usually CCR5 or CXCR4. As many microorganisms, HIV-1 also interacts with heparan sulfate (HS), a complex group of cell surface associated anionic polysaccharides. It has been thought that this binding, occurring at a step prior to CD4 recognition, increases infectivity by pre-concentrating the virion particles at the cell surface. Early work, dating from before the identification of CCR5 and CXCR4, showed that a variety of HS mimetics bind to the gp120 V3 loop through electrostatic interactions, compete with cell surface associated HS to bind the virus and consequently, neutralize the infectivity of a number of T-cell line-adapted HIV-1 strains. However, progress made to better understand HIV-1 attachment and entry, coupled with the recent identification of additional gp120 regions mediating HS recognition, have considerably modified this view. Firstly, the V3 loop from CXCR4-using viruses is much more positively charged compared to those using CCR5. HS inhibition of cell attachment is thus restricted to CXCR4-using viruses (such as T-cell line-adapted HIV-1). Secondly, studies aiming at characterizing the gp120/HS complex revealed that HS binding was far more complex than previously thought: in addition to the V3 loop of CXCR4 tropic gp120, HS interacts with several other cryptic areas of the protein, which can be induced upon CD4 binding, and are conserved amongst CCR5 and CXCR4 viruses. In view of these data, this review will detail the present knowledge on HS binding to HIV-1, with regards to attachment and entry processes. It will discuss the perspective of targeting the gp120 co-receptor binding site with HS mimetic compounds, a strategy that recently gave rise to entry inhibitors that work in the low nanomolar range, independently of co-receptor usage. PMID:24312095

  20. Replication of an acutely lethal simian immunodeficiency virus activates and induces proliferation of lymphocytes.

    PubMed Central

    Fultz, P N

    1991-01-01

    A variant of simian immunodeficiency virus from sooty mangabey monkeys (SIVsmm), termed SIVsmmPBj14, was previously identified and shown to induce acute disease and death within 1 to 2 weeks of inoculation of pig-tailed macaques and mangabey monkeys (P. N. Fultz, H. M. McClure, D. C. Anderson, and W. M. Switzer, AIDS Res. Hum. Retroviruses 5:397-409, 1989). SIVsmmPBj14 differed from its parent virus, SIVsmm9, not only in pathogenicity but also in multiple in vitro properties. As a first approach to understanding the biological and molecular mechanisms responsible for the acute disease and death induced by this variant, virus-host cell interactions of SIVsmmPBj14 and SIVsmm9 were studied. Initial rates of replication of the two viruses were identical in primary peripheral blood mononuclear cells (PBMC) from normal pig-tailed macaques and mangabey monkeys, but SIVsmmPBj14 infection always resulted in higher yields of virus than did SIVsmm9 infection, as assessed by levels of reverse transcriptase activity in culture supernatants. Surprisingly, despite its cytopathicity for macaque and mangabey CD4+ cells, replication of SIVsmmPBj14 was accompanied by up to 10-fold increases in number of viable cells compared with cell numbers in uninfected or SIVsmm9-infected cultures. Furthermore, SIVsmmPBj14 was shown to infect and replicate in resting PBMC just as efficiently as in mitogen-stimulated PBMC, irrespective of whether exogenous interleukin-2 (IL-2) or antibodies that neutralized IL-2 were added to culture media. Accumulation of virus in culture supernatants of resting PBMC preceded by several days the appearance of activated cells which expressed the IL-2 receptor alpha subunit (CD25), suggesting that activation of cells was not essential for replication. The ability to activate and to induce simian PBMC to proliferate appeared specific for the acutely lethal variant because incorporation of [3H]thymidine by PBMC from naive animals was observed only upon incubation with concentrated, heat-inactivated SIVsmmPBj14 and not with other viruses. Both CD4(+)- and CD8(+)-enriched cell populations proliferated in response to SIVsmmPBj14. These results are consistent with in vivo observations and suggest that the abilities both to replicate in resting cells and to induce lymphocytes to proliferate may contribute to the extreme virulence of SIVsmmPBj14. Images PMID:1870205

  1. Implications of tritium in neutral beam injectors

    SciTech Connect

    Kim, J; Stewart, L D

    1980-01-01

    Neutral injectors for heating plasmas of D-T burning fusion reactors are subject to tritium contamination. This paper discusses relevant questions and problem areas pertinent to tritium environment, including calculations of tritium contaminations in different neutral injectors, gas handling and pumping systems, and implications on beam line components.

  2. 32 CFR 644.323 - Neutral language.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...Defense 4 2010-07-01 2010-07-01 true Neutral language. 644.323 Section 644.323 National Defense Department...PROPERTY REAL ESTATE HANDBOOK Disposal § 644.323 Neutral language. Wherever the words “man”, “men”, or their...

  3. 32 CFR 644.323 - Neutral language.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...Defense 4 2011-07-01 2011-07-01 false Neutral language. 644.323 Section 644.323 National Defense Department...PROPERTY REAL ESTATE HANDBOOK Disposal § 644.323 Neutral language. Wherever the words “man”, “men”, or their...

  4. Reconciling niche and neutrality: the continuum hypothesis

    E-print Network

    LETTER Reconciling niche and neutrality: the continuum hypothesis Dominique Gravel,1 * Charles D, NY 12545, USA *Correspondence: E-mail: domgravl@globetrotter.net Abstract In this study, we ask if instead of being fundamentally opposed, niche and neutral theories could simply be located at the extremes

  5. Implications of Internet architecture on net neutrality

    Microsoft Academic Search

    Scott Jordan

    2009-01-01

    Net neutrality represents the idea that Internet users are entitled to service that does not discriminate on the basis of source, destination, or ownership of Internet traffic. The United States Congress is considering legislation on net neutrality, and debate over the issue has generated intense lobbying. Congressional action will substantially affect the evolution of the Internet and of future Internet

  6. A Technical Approach to Net Neutrality

    Microsoft Academic Search

    Xiaowei Yang; Gene Tsudik; Xin Liu

    2006-01-01

    A recent statement by AT&T CEO Ed Whitacre sparked considerable fear in the public that the Internet may not be open any more: the ISPs dictate which sites\\/applications flourish and which flounder. The state- ment triggered the heated debate on net neutrality and ignited the battle to enact net neutrality legislation. How - ever, by the date of writing, all

  7. The Dubious Value of Value Neutrality

    ERIC Educational Resources Information Center

    Balch, Stephen H.

    2006-01-01

    Hard science is properly value neutral. But when that ideological neutrality extends to the whole university, the traditional foundation crumbles. Steve Balch laments the moral vacuum that now substitutes for fundamental principles, because it is impossible to frame a program of education--especially in the humanities and social sciences--without…

  8. Neutral beam heating system for TFTR

    SciTech Connect

    Williams, M.D.; Eubank, H.P.; Grisham, L.R.; Kamperschroer, J.H.; Kugel, H.W.; Martin, G.D.; O'Connor, T.; Prechter, R.E.; Prichard, B.A.; Von Halle, A.

    1985-07-01

    The first two neutral injection beamlines have been installed on TFTR and are now operational. The operation of six ion sources producing either hydrogen or deuterium beams at energies up to 80 kilovolts has produced notable plasma heating results. Eventual neutral beam capability on TFTR should provide the energy necessary to demonstrate breakeven.

  9. JET neutral beam power upgrade Introduction

    E-print Network

    shutdown project · Hydraulic,vacuumcompatibilityandpower loading commissioning of the enhanced NB systemJET neutral beam power upgrade Introduction A tokamak is a complex assembly, a system of systems the challenging requirements that fusion demands. The neutral beam heating system and its upgrade for the JET

  10. Neutralizing Music Piracy: An Empirical Examination

    Microsoft Academic Search

    Jason R. Ingram; Sameer Hinduja

    2008-01-01

    The current study sought to test the viability of employing Sykes and Matza's (1957) techniques of neutralization as a framework for understanding online music piracy. Using data from a sample of 2,032 undergraduates from a large Midwestern university, the relevance of neutralization theory is tested via multinomial logistic regression while controlling for other theoretical predictors and demographic variables. The findings

  11. Neutral-particle-beam production and injection

    NASA Astrophysics Data System (ADS)

    Post, D.; Pyle, R.

    1982-07-01

    A discussion of the interactions of neutral beams with confined plasmas was presented. The production and diagnosis of the neutral beams was discussed. In general, atoms, molecules, and ions of the isotopes of hydrogen are examined, but some heavier elements (for example, oxygen) are mentioned. The emphasis will be on single particle collisions, selected atomic processes on surfaces is included.

  12. Sampling Hubbell's neutral theory of biodiversity

    Microsoft Academic Search

    David Alonso; Alan J. McKane

    2004-01-01

    In the context of neutral theories of community ecology, a novel genealogy-based framework has recently furnished an analytic extension of Ewens sampling multivariate abundance distribution, which also applies to a random sample from a local community. Here, instead of taking a multivariate approach, we further develop the sampling theory of Hubbell's neutral spatially implicit theory and derive simple abundance distributions

  13. Neutral depletion and the helicon density limit

    SciTech Connect

    Magee, R. M.; Galante, M. E.; Carr, J. Jr.; Lusk, G.; McCarren, D. W.; Scime, E. E. [West Virginia University, Morgantown, West Virginia 26506 (United States)] [West Virginia University, Morgantown, West Virginia 26506 (United States)

    2013-12-15

    It is straightforward to create fully ionized plasmas with modest rf power in a helicon. It is difficult, however, to create plasmas with density >10{sup 20} m{sup ?3}, because neutral depletion leads to a lack of fuel. In order to address this density limit, we present fast (1 MHz), time-resolved measurements of the neutral density at and downstream from the rf antenna in krypton helicon plasmas. At the start of the discharge, the neutral density underneath the antenna is reduced to 1% of its initial value in 15 ?s. The ionization rate inferred from these data implies that the electron temperature near the antenna is much higher than the electron temperature measured downstream. Neutral density measurements made downstream from the antenna show much slower depletion, requiring 14 ms to decrease by a factor of 1/e. Furthermore, the downstream depletion appears to be due to neutral pumping rather than ionization.

  14. Selection of a Rare Neutralization-Resistant Variant following Passive Transfer of Convalescent Immune Plasma in Equine Infectious Anemia Virus-Challenged SCID Horses?

    PubMed Central

    Taylor, Sandra D.; Leib, Steven R.; Carpenter, Susan; Mealey, Robert H.

    2010-01-01

    Vaccines preventing HIV-1 infection will likely elicit antibodies that neutralize diverse strains. However, the capacity for lentiviruses to escape broadly neutralizing antibodies (NAbs) is not completely understood, nor is it known whether NAbs alone can control heterologous infection. Here, we determined that convalescent immune plasma from a horse persistently infected with equine infectious anemia virus (EIAV) neutralized homologous virus and several envelope variants containing heterologous principal neutralizing domains (PND). Plasma was infused into young horses (foals) affected with severe combined immunodeficiency (SCID), followed by challenge with a homologous EIAV stock. Treated SCID foals were protected against clinical disease, with complete prevention of infection occurring in one foal. In three SCID foals, a novel neutralization-resistant variant arose that was found to preexist at a low frequency in the challenge inoculum. In contrast, SCID foals infused with nonimmune plasma developed acute disease associated with high levels of the predominant challenge virus. Following transfer to an immunocompetent horse, the neutralization-resistant variant induced a single febrile episode and was subsequently controlled in the absence of type-specific NAb. Long-term control was associated with the presence of cytotoxic T lymphocytes (CTL). Our results demonstrate that immune plasma with neutralizing activity against heterologous PND variants can prevent lentivirus infection and clinical disease in the complete absence of T cells. Importantly, however, rare neutralization-resistant envelope variants can replicate in vivo under relatively broad selection pressure, highlighting the need for protective lentivirus vaccines to elicit NAb responses with increased breadth and potency and/or CTL that target conserved epitopes. PMID:20392850

  15. Common variable immunodeficiency and idiopathic primary hypogammaglobulinemia: two different conditions within the same disease spectrum

    PubMed Central

    Driessen, Gertjan J.; Dalm, Virgil A.S.H.; van Hagen, P. Martin; Grashoff, H. Anne; Hartwig, Nico G.; van Rossum, Annemarie M. C.; Warris, Adilia; de Vries, Esther; Barendregt, Barbara H.; Pico, Ingrid; Posthumus, Sandra; van Zelm, Menno C.; van Dongen, Jacques J.M.; van der Burg, Mirjam

    2013-01-01

    Patients with hypogammaglobulinemia who do not fulfill all the classical diagnostic criteria for common variable immunodeficiency (reduction of two immunoglobulin isotypes and a reduced response to vaccination) constitute a diagnostic and therapeutic dilemma, because information concerning the clinical and immunological characteristics of these patients with idiopathic primary hypogammaglobulinemia is not available. In 44 common variable immunodeficiency and 21 idiopathic primary hypogammaglobulinemia patients we determined the clinical phenotypes and performed flow cytometric immunophenotyping to assess the pathophysiological B-cell patterns and memory B-cell subset counts. Age-matched B-cell subset reference values of 130 healthy donors were generated. Severe pneumonia and bronchiectasis occurred at similar frequencies in idiopathic primary hypogammaglobulinemia and common variable immunodeficiency. Although IgG levels were only moderately reduced compared to common variable immunodeficiency, 12 of 21 idiopathic primary hypogammaglobulinemia patients required immunoglobulin replacement. Non-infectious disease-related clinical phenotypes (autoimmune cytopenia, polyclonal lymphocytic proliferation and persistent unexplained enteropathy) were exclusively observed in common variable immunodeficiency and were associated with early peripheral B-cell maturation defects or B-cell survival defects. T-cell dependent memory B-cell formation was more severely affected in common variable immunodeficiency. Furthermore, 14 of 21 idiopathic primary hypogammaglobulinemia patients showed normal peripheral B-cell subset counts, suggestive for a plasma cell defect. In conclusion, idiopathic primary hypogammaglobulinemia patients who do not fulfill all diagnostic criteria of common variable immunodeficiency have moderately decreased immunoglobulin levels and often a normal peripheral B-cell subset distribution, but still suffer from serious infectious complications. PMID:23753020

  16. Evaluation of neurosyphilis in human immunodeficiency virus-infected individuals.

    PubMed

    Tomberlin, M G; Holtom, P D; Owens, J L; Larsen, R A

    1994-03-01

    The diagnosis of neurosyphilis in patients infected with the human immunodeficiency virus (HIV) remains problematic. We examined the use of the Treponema pallidum hemagglutination (TPHA) index and quantitative tests of CSF by means of microhemagglutination-T. pallidum for diagnosis of neurosyphilis in 58 HIV-infected persons with latent syphilis who had not recently received therapy for syphilis. Five patients (9%) had reactive CSF VDRL tests and thus had proven neurosyphilis. For 13 patients (22%), CSF findings were normal and revealed no evidence of neurosyphilis. For 40 patients (69%), abnormal CSF findings were characteristic of neurosyphilis, but their CSF VDRL tests were nonreactive. Twenty-five of the 40 patients with possible neurosyphilis had pleocytosis and elevated CSF levels of protein and/or IgG. Five (12.5%) of these 40 patients had positive TPHA indices that indicated intrathecal antitreponemal antibody production, a finding that provided greater support for the diagnosis of active neurosyphilis. With use of the TPHA index, patients with CSF abnormalities can be better classified in regard to their need for therapy for neurosyphilis. PMID:8011805

  17. Human immunodeficiency virus risk behavior among female substance abusers.

    PubMed

    Ramsey, Susan E; Bell, Kathryn M; Engler, Patricia A

    2010-04-01

    HIV is an increasingly critical and costly health problem for American women. Substance use plays a major role in human immunodeficiency virus (HIV) infection in women. There are several plausible explanations for the association between substance use and HIV risk behavior. Pregnant substance abusers are a population deserving special attention given the prevalence of risk behavior in this population and the added risk of perinatal transmission of HIV. Current guidelines for the screening and treatment of HIV among pregnant women and their infants are delineated. Substance abuse treatment has a limited impact on HIV risk behavior in female substance abusers. Similarly, traditional knowledge-based and skill-based HIV risk reduction interventions have modest efficacy in this population. Hence, there is a need to develop new interventions that directly target sex-related and drug-related HIV risk behavior among female substance abusers. Recent work suggests that the incorporation of motivational interviewing components into traditional HIV risk reduction interventions may be a promising new direction for the field. PMID:20407976

  18. RAG1/2 knockout pigs with severe combined immunodeficiency.

    PubMed

    Huang, Jiao; Guo, Xiaogang; Fan, Nana; Song, Jun; Zhao, Bentian; Ouyang, Zhen; Liu, Zhaoming; Zhao, Yu; Yan, Quanmei; Yi, Xiaoling; Schambach, Axel; Frampton, Jon; Esteban, Miguel A; Yang, Dongshan; Yang, Huaqiang; Lai, Liangxue

    2014-08-01

    Pigs share many physiological, biochemical, and anatomical similarities with humans and have emerged as valuable large animal models for biomedical research. Considering the advantages in immune system resemblance, suitable size, and longevity for clinical practical and monitoring purpose, SCID pigs bearing dysfunctional RAG could serve as important experimental tools for regenerative medicine, allograft and xenograft transplantation, and reconstitution experiments related to the immune system. In this study, we report the generation and phenotypic characterization of RAG1 and RAG2 knockout pigs using transcription activator-like effector nucleases. Porcine fetal fibroblasts were genetically engineered using transcription activator-like effector nucleases and then used to provide donor nuclei for somatic cell nuclear transfer. We obtained 27 live cloned piglets; among these piglets, 9 were targeted with biallelic mutations in RAG1, 3 were targeted with biallelic mutations in RAG2, and 10 were targeted with a monoallelic mutation in RAG2. Piglets with biallelic mutations in either RAG1 or RAG2 exhibited hypoplasia of immune organs, failed to perform V(D)J rearrangement, and lost mature B and T cells. These immunodeficient RAG1/2 knockout pigs are promising tools for biomedical and translational research. PMID:24973446

  19. Adrenal disorders in human immunodeficiency virus (HIV) infected patients.

    PubMed

    Bons, Justine; Moreau, Lucile; Lefebvre, Hervé

    2013-12-01

    Human Immunodeficiency Virus (HIV) infection is associated with adrenal disorders, which must not be underestimated. Adrenal morphologic changes are primarily related to opportunistic infections, mostly by cytomegalovirus and mycobacteria, and malignant tumours such as non-Hodgkin's lymphoma and Kaposi's sarcoma. The most frequent biological alteration reported to date is the increases in cortisol concentrations which results from a decrease in cortisol metabolism and hyperactivity of the hypothalamo-pituitary-adrenal axis commonly referred to as pseudo-Cushing's syndrome. These modifications can be a consequence of antiretroviral therapy and do not require any investigation or specific treatment. Conversely, adrenal insufficiency, either iatrogenic or secondary to glandular infiltration by neoplasms or infections, needs long-term substitution with hydrocortisone, but at present occurs more rarely and usually at late stages of disease progression. The impact of HIV infection on the other adrenocortical functions has been less reported in the literature although several studies show low levels of adrenal androgens, especially dehydroepiandrostenedione (DHEA). Impairment in mineralocorticoid function appears occasional and remains a subject of debate. PMID:24262982

  20. Successful treatment for West syndrome with severe combined immunodeficiency.

    PubMed

    Motobayashi, Mitsuo; Inaba, Yuji; Fukuyama, Tetsuhiro; Kurata, Takashi; Niimi, Taemi; Saito, Shoji; Shiba, Naoko; Nishimura, Takafumi; Shigemura, Tomonari; Nakazawa, Yozo; Kobayashi, Norimoto; Sakashita, Kazuo; Agematsu, Kazunaga; Ichikawa, Motoki; Koike, Kenichi

    2015-01-01

    Several immune mechanisms are suspected in the unknown etiology of West syndrome (WS). We report a male infant who suffered from WS and X-linked T-B+NK- severe combined immunodeficiency (X-SCID) with a missense mutation of the IL2RG gene (c.202G>A, p.Glu68Lys). He promptly began vitamin B6 and valproic acid treatment, but infantile spasms (IS) and hypsarrhythmia persisted. Administration of intravenous immunoglobulin and the change to topiramate (TPM) at 7 months of age resulted in the rapid resolution of IS. The CD4/8 ratio in his peripheral blood increased from 0.04-0.09 to 0.20-1.95 following unrelated cord blood transplantation (UCBT). In vitro lymphocyte proliferation in response to phytohemagglutinin or concanavalin A and the ability of B lymphocytes to produce antibodies improved as well. Electroencephalogram findings became normal 1 month after UCBT. Thus, we consider that T-cell dysfunction and/or impairments in T-B cell interactions due to X-SCID may have played important roles in the onset of WS. Immune-modulating therapies along with the administration of TPM effectively treated this severe epileptic syndrome in our patient. PMID:24534054