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)

The low copy number of human immunodeficiency virus 1 (HIV-1) DNA infected cells precludes routine detection by in situ hybridization. The inability to detect cells latently infected by HIV-1 makes difficult the study of factors that induce viral transcription, an essential factor in the development of the acquired immune deficiency syndrome (AIDS). A sensitive and rapid technique to detect HIV-1 DNA could be used as a diagnostic test for AIDS and to differentiate latent versus active viral infection. We describe a 3-h technique whereby HIV-1 DNA is amplified by hot start polymerase chain reaction (PCR) and detected directly in infected cells. The specificity of the assay was demonstrated by double labeling the positive cells with CD4. Using a CR10 HIV-1-infected cell line, the 90% of cells that were HIV-1 DNA positive could be distinguished from the 10% that were actively expressing HIV-1 RNA. The PCR in situ technique should allow for the direct localization of DNA sequences in cells that would otherwise be undetectable by conventional in situ analysis.
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PMID:Rapid in situ detection of PCR-amplified HIV-1 DNA. 136 73

The cell-surface antigen CD4 plays a pivotal role in the class II MHC-restricted response of specific T lymphocytes, and serves as the major receptor of human immunodeficiency virus (HIV). The recent elucidation of CD4 function in physiological and pathological conditions has improved prospects for CD4-targeted immune therapy by facilitating the design of therapeutic strategies aimed at blocking CD4 function, delivering immunosuppressive signals via this receptor molecule, or selectively depleting CD4+ cells.
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PMID:CD4-targeted immune intervention: a strategy for the therapy of AIDS and autoimmune disease. 136 92

CD4 is critical for the development and function of the CD4+ subset of T cells and also subserves as the receptor for the human immunodeficiency viruses. Reports in the past year clarify the role and the molecular interactions of CD4 in these events. Determination of the structure of an extracellular fragment of CD4 reveals novel variations of the immunoglobulin fold and provides an atomic framework for interpretation of its interactions with MHC class II molecules and with gp120, the external envelope glycoprotein of the human immunodeficiency virus.
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PMID:CD4: its structure, role in immune function and AIDS pathogenesis, and potential as a pharmacological target. 136 82

Contact of human immunodeficiency virus (HIV)-infected MOLT-4 lymphocytes with epithelial cells derived from small intestine (I407; Intestine 407) resulted in a rapid polar budding of viral particles into an enclosed space formed by interdigitating microvilli of the contacting cells. Electron microscopy showed that released HIV was taken up into the mucosal cell via three independent mechanisms: (1) phagocytosis, (2) coated pits, and (3) direct fusion. Morphological evidence suggests that internalized HIV may escape into the cytoplasm of the target cell by uncoating at the endosomal membrane. Based on CD4 antibody binding and CD4 antibody blocking experiments, HIV entry does not appear to be mediated by a viral CD4 receptor. Productivity of I407 infection was confirmed by virus isolation from cocultured MT-4 lymphocytic cells, reverse transcriptase assay, p24 antigen ELISA, in situ HIV mRNA hybridization, and Southern dot blot analysis. Contrary to infection with free virus, the cell-to-cell infection was not blocked by anti-gp120 or antiviral serum from HIV-positive individuals. It appears that HIV transmission within the confined space between contacting cells enables HIV to evade immune protection provided by neutralizing antibodies. Our results reveal a mechanism of HIV infection of epithelial cells which is triggered by cell-cell contact. Furthermore, these observations offer an insight into the cellular sequence of events which may take place during sexual transmission of HIV across an intact epithelial barrier.
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PMID:Mechanism of HIV spread from lymphocytes to epithelia. 137 Jan 28

Two monoclonal antibodies designated BAT085 and G3-136 were raised by immunizing BALB/c mice with gp120 purified from human immunodeficiency virus type 1 (HIV-1) IIIB-infected H9 cell extracts. Among three HIV-1 laboratory isolates (IIIB, MN, and RF), BAT085 neutralized only IIIB infection of CEM-SS cells, whereas G3-136 neutralized both IIIB and RF. These antibodies also neutralized a few primary HIV-1 isolates in the infection of activated human peripheral blood mononuclear cells. In indirect immunofluorescence assays, BAT085 bound to H9 cells infected with IIIB or MN, while G3-136 bound to H9 cells infected with IIIB or RF, but not MN. Using sequence-overlapping synthetic peptides of HIV-1 IIIB gp120, the binding site of BAT085 and G3-136 was mapped to a peptidic segment in the V2 region (amino acid residues 169 to 183). The binding of these antibodies to immobilized gp120 was not inhibited by the antibodies directed to the principal neutralization determinant in the V3 region or to the CD4-binding domain of gp120. In a competition enzyme-linked immunosorbent assay, soluble CD4 inhibited G3-136 but not BAT085 from binding to gp120. Deglycosylation of gp120 by endo-beta-N-acetylglucosaminidase H or reduction of gp120 by dithiothreitol diminished its reactivity with G3-136 but not with BAT085. These results indicate that the V2 region of gp120 contains multiple neutralization determinants recognized by antibodies in both a conformation-dependent and -independent manner.
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PMID:Identification and characterization of a neutralization site within the second variable region of human immunodeficiency virus type 1 gp120. 137 May 58

To identify the principal neutralization determinant (PND) of simian immunodeficiency virus (SIV), antisera were generated using recombinant gp110 [the SIV analog of the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein, gp120], gp140, several large recombinant and proteolytic envelope fragments, and synthetic peptides of the SIVmac251 isolate. When purified under conditions that retain its native structure, gp110 bound CD4 and elicited antisera that neutralized SIVmac251 with high titer. Native gp110 also completely inhibited neutralizing antibody in sera from SIVmac251-infected macaques. In contrast, denatured gp110 and gp140, large envelope fragments, and synthetic peptides (including peptides analogous to the HIV-1 PND) elicited very low or undetectable neutralizing antibody titers and did not inhibit neutralizing antibody in infected macaque sera. Enzymatically deglycosylated gp110 efficiently absorbed neutralizing antibodies from macaque sera, showing that neutralizing antibodies primarily bind the protein backbone. A 45-kDa protease digest product, mapping to the carboxyl-terminal third of gp110, also completely absorbed neutralizing antibodies from infected macaque sera. These results show that the PND(s) of this SIV isolate depends on the native conformation and that linear peptides corresponding to the V3 loop of SIV envelope, in contrast to that of HIV-1, do not elicit neutralizing antibody. This may affect the usefulness of SIVmac for evaluating HIV-1 envelope vaccine approaches that rely on eliciting neutralizing antibody.
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PMID:The principal neutralization determinant of simian immunodeficiency virus differs from that of human immunodeficiency virus type 1. 137 58

While expression of complement receptor 2 (CR2) (CD21) on some CD4+ cell lines renders them more susceptible to infection by complement-treated human immunodeficiency virus (HIV), coexpression of CR2 and CD4 on peripheral blood lymphocytes has not, until recently, been observed. Several recent studies, however, have found that human T lymphocytes express low levels of CR2. Additionally, complement treatment of HIV before addition to these cells has been reported to increase virus expression in peripheral blood lymphocyte cultures. These findings suggest that complement-mediated enhancement of infection of human T cells could occur in vivo and have prompted us to examine both the phenotypic properties of CD4+CR2+ T cells in healthy persons and the expression of CR2 on CD4+ lymphocytes during HIV infection. As was previously reported, we observed CR2 on a proportion (10-50%) of both CD8+ and CD4+ T cells. Approximately half of CD4+CR2+ cells expressed the memory cell markers CD45RO and CD29, 80% expressed the naive marker CD45RA, while 22% expressed CD25. These values were not substantially different from total CD4+ cells. Stimulation of lymphocytes with phytohaemagglutinin (PHA), OKT3 or calcium ionophore but not with phorbol myristate acetate (PMA) or interleukin-2 (IL-2) decreased expression of CR2 on CD4 cells by half over a 3-day culture period. The per cent of CD4+ cells expressing CR2 was significantly decreased in patients with asymptomatic and symptomatic HIV infection compared to uninfected control donors (P = 0.0001). In contrast, the decrease in CR2 expression was not observed with CD8+ lymphocytes from HIV-infected persons. These results confirm that CR2 is expressed on human T lymphocytes and suggest that a subset of CD4+ lymphocytes is selectively affected in HIV-infected individuals.
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PMID:Phenotypic analysis of complement receptor 2+ T lymphocytes: reduced expression on CD4+ cells in HIV-infected persons. 137 93

Human endothelial cells isolated from hepatic sinusoids were infected in vitro with human immunodeficiency virus type 1 (HIV-1). An early sign of infection occurring in the culture was the formation of multinucleated cells. By double-labeling immunofluorescence, 5-15% of the cells recognized as endothelial cells owing to the presence of von Willebrand factor were found to contain HIV p24 and gp120 antigens after 2 weeks. Reverse transcriptase activity was released into the medium, and different steps in the process of viral budding were observed by electron microscopy. The virus produced by the endothelial cells was found to be infectious for CEM cells, a human T-cell line. CD4 molecules are present at the surface of the endothelial cells, as demonstrated by immunogold-silver staining and backscattered electron imaging. Treatment with an anti-CD4 antibody abolished productive infection of the sinusoidal endothelial cells. The possibility that endothelial cells of the liver sinusoid are infected in vivo with HIV remains to be clearly shown.
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PMID:Primary cultures of endothelial cells from the human liver sinusoid are permissive for human immunodeficiency virus type 1. 137 78

Isotype and binding characteristics of T cell-reactive antilymphocyte antibodies (ALA) were investigated in 287 human immunodeficiency virus (HIV)+ sera from patients with CDC II to IVC clinical disease. Using purified soluble T-lymphoblast (CEM cell line) membranes and an ELISA method, 29 HIV+ sera showed significant reactions with this substrate and a selective expression of IgG-ALA was detected in 7 HIV+ sera. Subsequent microcytotoxicity assays, utilizing peripheral T lymphocytes and CEM cells as targets, demonstrated no significant cytotoxic capability in such sera, whereas 12 of 17 HIV+ serum samples with IgM-ALA ELISA reactivities showed a significant degree of killing in the Terasaki test. Further experiments of saturation of CD4 molecules on CEM extract by OKT4 monoclonal antibody (MoAb) induced a high inhibition of IgG-ALA binding to the T-cell membranes in only two IgG-ALA+ sera (No. 93, CDC III; No. 179, CDC II stage). Conversely, treatment of CEM membrane lysate with Leu3a MoAb, specific for the gp120 reactive domain of the HIV receptor, failed to prevent membrane binding in all seven of the IgG-ALA+ sera. Following the adsorption of serum 93 on a T-cell membrane antigen affinity column, SDS-PAGE analysis demonstrated that the predominant ALA material reacting with T-cell membranes was IgG with no detectable traces of IgM. These data provide evidence that ALA in HIV+ patients may be simultaneously or selectively expressed as IgG and/or IgM with different properties.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential isotype expression and binding properties of T cell-reactive antibodies in human immunodeficiency virus (HIV) infection. 137 49

Neutralization of human immunodeficiency virus type 1 (HIV-1) infection with soluble CD4 (sCD4) can be achieved over a broad range of concentrations for different virus strains. Laboratory virus strains passaged in transformed T-cell lines are typically sensitive to sCD4 neutralization, whereas primary virus isolates require over 100-fold-higher sCD4 concentrations. Using recombinant viruses generated from a laboratory strain, HIV-1NL4-3, and a primary macrophagetropic strain, HIV-1JR-FL, we mapped a region of gp120 important for determining sensitivity to sCD4 neutralization. This same region has previously been defined as important for macrophage and transformed T-cell line tropism and includes the V3 neutralization domain but does not include regions of gp120 that have been shown to be most important for CD4 binding.
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PMID:Mapping genetic determinants for human immunodeficiency virus type 1 resistance to soluble CD4. 137 3


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