Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibitory effects of human immunodeficiency virus (HIV) on T lymphocyte function have been linked to perturbation of signaling through the T cell antigen receptor-CD3 complex. Comparative biochemical analyses of signaling responses were performed in T cells that were either uninfected or chronically infected with the HIV-1/IIIB strain. Stimulation with antibodies to CD3 triggered both Ca2+ accumulation and phosphoinositide hydrolysis responses that were equivalent in uninfected and infected cells. Treatment with anti-CD3 or with phorbol diester also stimulated serine phosphorylation of CD4 molecules in uninfected T cells. However, phosphorylation of CD4 was not observed after anti-CD3 treatment in HIV-infected T cells despite normal phosphorylation responses to phorbol diester. Identical results were obtained using a T cell line that was infected with an env (gp160/120-) HIV-1 defective variant. These studies indicate that infection with HIV-1 inhibits the activation of protein kinase associated with the T cell receptor-CD3 complex by a mechanism which is independent of viral env protein components.
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PMID:Inhibition of T cell antigen receptor-dependent phosphorylation of CD4 in human immunodeficiency virus type 1 infected cells. 131 Sep 88

Cats were vaccinated with one of the three preparations: purified feline immunodeficiency virus (FIV) incorporated into immune stimulating complexes (ISCOMs), recombinant FIV p24 ISCOMs, or a fixed, inactivated cell vaccine in quil A. Cats inoculated with the FIV ISCOMs or the recombinant p24 ISCOMs developed high titres of antibodies against the core protein p24 but had no detectable antibodies against the env protein gp120 or virus neutralising antibodies. In contrast, all of the cats inoculated with the fixed, inactivated cell vaccine developed anti-env antibodies and four of five had detectable levels of neutralising antibody. However, none of the vaccinated cats were protected from infection after intraperitoneal challenge with 20 infectious units of FIV. Indeed there appeared to be enhancement of infection after vaccination as the vaccinated cats become viraemic sooner than the unvaccinated controls, and 100% of the vaccinated cats became viraemic compared with 78% of the controls. The mechanism responsible for this enhancement remains unknown.
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PMID:Enhancement after feline immunodeficiency virus vaccination. 133 97

The envelope protein of the feline immunodeficiency virus (FIV) was analyzed using several epitope prediction programs based on profiles of hydrophilicity, antigenicity, and probability of residues to lie on the protein surface. Tentative homologies with the immunodominant epitope sites in simian virus (SIV) or human immunodeficiency virus (HIV) such as the V3 loop, the site of cleavage between surface envelope protein (SU) and transmembrane envelope protein (TM), and sites of N-glycosylation were thus identified. Five peptides corresponding to potential epitopes were synthesized. Four out of five peptides (P99, P100, P101, P103) were from the FIV surface envelope protein (SU). The last one (P102) was from the FIV transmembrane envelope protein TM. Three of these peptides (P99, P100, and P102) were recognized in ELISA by almost all the sera from infected cats. The peptide from TM (102) was recognized by sera from both naturally infected and inoculated cats, whereas peptides P99 and P100 (from SU) were recognized mainly by sera from naturally infected cats. On the basis of these results we propose that peptides P99, and P100 from SU and P102 from TM constitute epitopes on the FIV env protein.
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PMID:Localisation of three epitopes of the env protein of feline immunodeficiency virus. 137 40

Monoclonal antibodies (MAbs) were raised against the transmembrane protein (TM) gp41 of human immunodeficiency virus type 1 (HIV-1, strain HTLV-IIIB). The reactivity of three TM-specific MAbs was investigated in several tests, ELISA, immunostaining of Western blots, immunofluorescence and an alkaline phosphatase-anti-alkaline phosphatase assay. Epitope mapping was done by using overlapping gp41 peptides produced as Escherichia coli fusion proteins and synthetic peptides. In an in vitro assay, all three MAbs showed enhancing effects on HIV-1 infection after single or repeated treatment with the purified MAbs at concentrations of 6 to 25 micrograms/ml. The enhancing domain is located between amino acids 724 and 752 of the env protein sequence. Homologous peptides based on this sequence were used for analysis of sera from 100 individuals at different stages of HIV infection to evaluate the relevance of antibodies against this region to the prognosis of disease. No antibodies reactive with this region were found in ELISA, indicating that this domain is not immunogenic in humans.
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PMID:Murine monoclonal antibodies directed against the transmembrane protein gp41 of human immunodeficiency virus type 1 enhance its infectivity. 137 82

The lysis of infected host cells by virus-specific cytolytic T lymphocytes (CTL) is an important factor in host resistance to viral infection. An optimal vaccine against human immunodeficiency virus type 1 (HIV-1) would elicit virus-specific CTL as well as neutralizing antibodies. The induction by a vaccine of HIV-1-specific CD8+ CTL in humans has not been previously reported. In this study, CTL responses were evaluated in HIV-1-seronegative human volunteers participating in a phase I acquired immune deficiency syndrome (AIDS) vaccine trial involving a novel vaccine regimen. Volunteers received an initial immunization with a live recombinant vaccinia virus vector carrying the HIV-1 env gene and a subsequent boost with purified env protein. An exceptionally strong env-specific CTL response was detected in one of two vaccine recipients, while modest but significant env-specific CTL activity was present in the second vaccinee. Cloning of the responding CTL gave both CD4+ and CD8+ env-specific CTL clones, permitting a detailed comparison of critical functional properties of these two types of CTL. In particular, the potential antiviral effects of these CTL were evaluated in an in vitro system involving HIV-1 infection of cultures of normal autologous CD4+ lymphoblasts. At extremely low effector-to-target ratios, vaccine-induced CD8+ CTL clones lysed productively infected cells present within these cultures. When tested for lytic activity against target cells expressing the HIV-1 env gene, CD8+ CTL were 3-10-fold more active on a per cell basis than CD4+ CTL. However, when tested against autologous CD4+ lymphoblasts acutely infected with HIV-1, CD4+ clones lysed a much higher fraction of the target cell population than did CD8+ CTL. CD4+ CTL were shown to recognize not only the infected cells within these acutely infected cultures but also noninfected CD4+ T cells that had passively taken up gp120 shed from infected cells and/or free virions. These results were confirmed in studies in which CD4+ lymphoblasts were exposed to recombinant gp120 and used as targets for gp120-specific CD4+ and CD8+ CTL clones. gp120-pulsed, noninfected targets were lysed in an antigen-specific fashion by CD4+ but not CD8+ CTL clones. Taken together, these observations demonstrate that in an in vitro HIV-1 infection, sufficient amounts of gp120 antigen are produced and shed by infected cells to enable uptake by cells that are not yet infected, resulting in the lysis of these noninfected cells by gp120-specific, CD4+ CTL.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparative clonal analysis of human immunodeficiency virus type 1 (HIV-1)-specific CD4+ and CD8+ cytolytic T lymphocytes isolated from seronegative humans immunized with candidate HIV-1 vaccines. 146 Apr 17

Genetic diversity is a hallmark of the human immunodeficiency virus (HIV) genome, but the role of distinct HIV variants in the development of AIDS is unclear. Envelope (env) is the most highly variable gene in HIV as well as in other retroviruses. We have previously demonstrated that variation in simian immunodeficiency virus (SIV) env is primarily localized in two regions (V1 and V4) during progression to simian AIDS. To determine whether there is a common genotype that evolves as AIDS develops, a total of 160 SIV env genes isolated directly from the tissue DNAs of four macaques infected with cloned virus were compared. Common amino acid sequence changes were identified within V1, V4, and, in the late stages of disease, near V3. At several positions, the same amino acid change was seen frequently in the variant genomes from all four animals. As AIDS developed, the majority of viruses evolved an extended sequence in V1 that was rich in serine and threonine residues and shared similarity with proteins modified by O-linked glycosylation. Several of the predominant common sequence changes in V1 and V4 created new sites for N-linked glycosylation. Thus, common features of the SIV variants that evolve during progression to AIDS are motifs that potentially allow for structural and functional changes in the env protein as a result of carbohydrate addition.
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PMID:Alterations in potential sites for glycosylation predominate during evolution of the simian immunodeficiency virus envelope gene in macaques. 152 47

SIV infection in macaques has become an important animal model for HIV-1 infection in humans. An antibody assay was therefore developed and compared to a commercially available antigen assay with respect to their usefulness to monitor the course of simian immunodeficiency virus (SIV) infection in cynomolgus monkeys. A peptide, JB6T, consisting of 21 amino acids with the sequence NSWGCAFRQVCHTTVPWVNDS corresponding to a segment in the env protein of human immunodeficiency virus (HIV) type 2 was used as antigen in an enzyme-linked immunosorbent assay (ELISA). JB6T was found to detect IgG and IgM antibodies to viral antigens with high specificity. The earliest anti-SIV IgM antibodies were detected at days 13-16, with a maximum at day 20 and subsequently the levels fell. Specific IgG antibody levels increased at day 16-20 after SIV infection and reached a plateau at day 60. The commercially available HIV-1 p24/26 antigen test could, due to cross-reactivity, be employed to detect SIV antigen delay, peak and duration.
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PMID:Early appearance of simian immunodeficiency virus (SIV) antigen and antibodies as variables in evaluating antiviral drugs in macaques. 153

A cell clone, L-2, which produces non-infectious doughnut-shaped human immunodeficiency virus type 1 (HIV-1) particles, was permissive for HIV-1 superinfection, which resulted in the production of infectious particles. The superinfection showed slow kinetics compared with primary HIV-1 infection of M10 cells, the parent of the L-2 cell clone. Inhibition studies on the superinfection of L-2 cells using several CD4-related reagents showed that the CD4 molecule was an essential component of the receptor for superinfection. Strong inhibitory effects were obtained using CD4 peptides such as CD4(68-130), which includes a portion homologous to the immunoglobulin third complementarity-determining region (CDR3), as well as recombinant soluble CD4. In contrast, a CD4(45-60) peptide, which includes most of the CDR2-related region, was not effective, although the Leu-3a monoclonal antibody (MAb), which recognizes a site near the CDR2-related region, did slightly, but significantly, delay the superinfection kinetics. Comparative flow cytometry of L-2 and M10 cells revealed that the cell surface of L-2 cells despite expressing HIV-1 env protein, reacted slightly with OKT4 or anti-CD4(68-130) MAb, but not with Leu-3a or OKT4A MAb. In contrast, no reaction was detected with any of these anti-CD4 MAbs on the surface of another HIV-1 superinfection-resistant cell clone, MOLT-#8IIIB-14, which expresses HIV-1 env proteins but does not produce infectious HIV-1 particles. These results strongly suggest that expression of the CD4 major receptor site for primary HIV-1 infection is preferentially decreased on the surface of L-2 cells, but that the OKT4 epitope and the nearby region corresponding to immunoglobulin CDR3 remain exposed on the cell surface. Consequently, the CD4 CDR3-related region could play a major role as the receptor for the superinfection reported here.
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PMID:Human immunodeficiency virus type 1 (HIV-1) superinfection of a cell clone converting it from production of defective to infectious HIV-1 is mediated predominantly by CD4 regions other than the major binding site for HIV-1 glycoproteins. 162 1

We have been studying the role of human cytomegalovirus (HCMV) as a potential cofactor in human immunodeficiency virus (HIV)-related disease. The clinical relevance of HCMV is highlighted by the fact that it is a principal viral pathogen in patients with AIDS and is known to infect the same cells as HIV. In this study, we focused on the molecular interactions between HIV and HCMV in human fibroblasts and in the human glioblastoma/astrocytoma-derived cell line U373 MG, cells which can be productively infected by both viruses. Because these cells are CD4-, we used HIV pseudotyped with a murine amphotropic retrovirus as described previously (D. H. Spector, E. Wade, D. A. Wright, V. Koval, C. Clark, D. Jaquish, and S. A. Spector, J. Virol. 64:2298-2308, 1990). Initial studies showed that when cells were preinfected with HIV (Ampho-1B) for 5 days and then superinfected with HCMV, HIV antigen production dropped significantly in the coinfected cells but continued to rise in cells infected with HIV (Ampho-1B) alone. HCMV production, however, was unaffected by the presence of HIV. Further analysis showed that HIV steady-state RNA levels and gag and env protein production were also inhibited in the presence of HCMV. The transcriptional inhibition of HIV was particularly surprising in view of the previous results of several other laboratories as well as our own that HCMV infection stimulates HIV long terminal repeat-chloramphenicol acetyltransferase (LTR-CAT) expression in transient expression assays. To investigate this further, we transfected the HIV LTR-CAT construct into either uninfected cells or cells which had been preinfected with HIV. The cells were infected with HCMV 24 h posttransfection and assayed for CAT gene expression at 48 h after HCMV infection. Although there was some stimulation of the LTR-CAT in cells that were dually infected by HIV and HCMV, it was 16-fold less than that in the cells infected only with HCMV. This suggests that in the presence of the HIV infection, the stimulation of the HIV LTR-CAT gene by HCMV is significantly reduced. Experiments with UV-irradiated HCMV and the HCMV DNA polymerase inhibitor ganciclovir showed that HCMV transcription is necessary for the reduction in HIV production to occur; however, replication of the HCMV genome or any events which take place after DNA replication are not necessary. These results, coupled with the observation that inhibition is usually first seen between 8 and 24 h after HCMV infection, suggest that an HCMV early protein is involved in repression of HIV.
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PMID:Human cytomegalovirus inhibits human immunodeficiency virus replication in cells productively infected by both viruses. 165 86

A recombinant vaccinia virus in which the transcription of the human immunodeficiency virus type 1 (BRU isolate) env gene is driven by the 11K late vaccinia promoter yields about 10-fold higher amounts of gp160 env protein upon infection of monkey cells than does a recombinant in which gp160 is expressed using the 7.5K early-late promoter. The gp160 was purified from detergent lysates of infected cells by lentil lectin affinity chromatography followed by immunoaffinity chromatography, and was obtained in yields of 1-2 mg/10(9) cells of material estimated to be about 70% pure. Pairs of rabbits were immunized with purified gp160 using either one of five different adjuvants or an immunostimulating complex. In all cases a substantial humoral immune response was obtained after boosting, including an activity that neutralized the homologous (BRU) isolate of HIV-1. In some cases, this activity also neutralized two distantly related isolates, SF2 and MN.
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PMID:Cross-neutralizing antibodies in rabbits immunized with HIV-1 gp160 purified from simian cells infected with a recombinant vaccinia virus. 174 74


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