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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection with the human immunodeficiency virus (HIV-1) leads to a wide range of immunological abnormalities. We have shown that native envelope glycoproteins (gp120) of HIV-1 inhibit antigen-specific and anti-CD3 induced lymphoproliferation of normal lymphocytes. We have demonstrated that gp120 binds to CD4 positive T lymphocytes and is internalized. These studies suggest that interaction of gp120 with the CD4 receptor may be sufficient to inhibit antigen-specific T cell responses that are mediated via the CD3-Ti receptor complex. Such an event could represent another mechanism by which the overall immune function of the CD4 positive T lymphocyte is depressed and may be relevant in planning investigations on the ongoing vaccine trial involving envelope glycoproteins.
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PMID:Inhibitory influences of envelope glycoproteins of HIV-1 on normal immune responses. 285 50

Masking of host cell receptors following retroviral infection is the basis for the phenomenon of virus interference. Amphotropic retrovirus vectors were used to express the HIV envelope glycoprotein in a human CD4+ cell line. Envelope expression is accompanied by a reduction in the level of surface CD4 receptor molecules and correlates with the presence of intracellular envelope-CD4 receptor complexes. Cells expressing the HIV envelope acquire a cytolysis-resistant phenotype such that infection with HIV leads to a non-cytopathic persistent virus infection. Furthermore, phorbol ester-mediated stimulation of viral replication in persistently infected cells results in renewed cytolytic effects which, due to the absence of CD4 in the cell population, are absolutely independent of syncytium formation. This study elucidates the mechanism by which viral persistence is initiated and maintained in the course of AIDS.
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PMID:Envelope glycoprotein of HIV induces interference and cytolysis resistance in CD4+ cells: mechanism for persistence in AIDS. 296 82

Binding of the human immunodeficiency virus (HIV) to infectable host cells, such as B and T lymphocytes, monocytes and colorectal cells, is mediated by a high-affinity interaction between the gp120 component of the viral envelope glycoprotein and the CD4 receptor. Upon binding, it is thought that the second component of the envelope, gp41, mediates fusion between the viral envelope and host cell membranes. However, the early steps of HIV infection have not yet been thoroughly elucidated. Viral entry was first reported to be mediated by pH-dependent receptor-mediated endocytosis; subsequent studies have shown entry to be pH-independent. Although direct fusion of virus to plasma membranes of infected cells has been observed by electron microscopy, it is still formally possible that the infectious path of the virus involves receptor-mediated endocytosis. To gain a better understanding of receptor function in viral entry, we have analysed the ability of several altered or truncated forms of CD4 to serve as effective viral receptors. Our results indicate that domains beyond the HIV-binding region of CD4 are not required for viral infection. Some of the altered forms of CD4 that serve as effective HIV receptors are severely impaired in their ability to be endocytosed. These experiments therefore support the notion that viral fusion to the plasma membrane is sufficient for infection.
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PMID:Internalization of the human immunodeficiency virus does not require the cytoplasmic domain of CD4. 326 Mar 53

The expression of a human immunodeficiency virus (HIV) type 1 provirus (F12-HIV) cloned from a nonproducer, chronically infected CD4 down-regulated Hut-78 cell clone (F12) does not lead to the formation of viral particles and, upon transfection in HeLa CD4+ cells, confers resistance to HIV superinfection without affecting the CD4 receptor exposure. In an attempt to transfer the anti-HIV properties of F12-HIV into human primary cell, we constructed a Moloney murine leukemia virus-based retroviral vector containing an F12-HIV genome lacking the 3' long terminal repeat and part of the nef gene, which was expressed under the control of its 5' long terminal repeat. The F12-HIV genome was inserted in the orientation opposite to that of the murine leukemia virus transcriptional unit and was designated the N2/F12-HIV nef-antisense vector. Lymphoblastoid CEMss cells, as well as human peripheral blood lymphocytes, were successfully transduced by the recombinant retrovirus emerging from the producer PA317 clones. CEMss clones expressing the F12-HIV nef-antisense vector became resistant to HIV superinfection even at the highest utilized multiplicity of infection (10(5) 50% tissue culture infective doses per 10(6) cells). In transduced CEMss cells the viral interference induced by the F12-HIV expression is not due to CD4 HIV receptor down-regulation. Nonproducer, interfering HIV proviruses transduced into retroviral vectors may, therefore, provide an alternative strategy for the protection of CD4+ human primary cells from HIV infection, which strategy may be used in designating a safe and efficient gene therapy protocol for patients with AIDS.
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PMID:A nonproducer, interfering human immunodeficiency virus (HIV) type 1 provirus can be transduced through a murine leukemia virus-based retroviral vector: recovery of an anti-HIV mouse/human pseudotype retrovirus. 747 70

Levels of natural antibodies (NAb) with high anti-trinitrophenyl (TNP) activity are increased during human immunodeficiency virus (HIV) infection. The aim of the present study was to examine the anti-HIV effect of natural anti-TNP antibodies, as well as that of their internal image, TNP antigen, on HIV infection in vitro. The results obtained with anti-TNP antibodies, as assessed by syncytia formation, were variable, although they demonstrated an inhibitory effect. In contrast, using RT activity assay plus evaluation of syncytia formation and the viral cytopathic effect, we found that bovine serum albumin (BSA) bearing different TNP groups was able to inhibit HIV infection of peripheral mononuclear cells and T4 cell lines without affecting cell metabolism or proliferation. BSA alone was devoid of activity; the antiviral effect depended on TNP substitution of the BSA molecule, and passage through an anti-TNP immunoadsorbent abolished this effect. The mechanism by which TNP exerts this antiviral effect is unclear. Antigenic epitopes may be shared by HIV and TNP, since monoclonal antibodies directed against various HIV proteins reacted with TNP in an enzyme immunoassay. TNP-BSA, however, did not bind to the CD4 receptor.
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PMID:Inhibition of in vitro HIV infection by trinitrophenyl-protein conjugates. 748 Oct 74

Infection of T cell lines by the type 1 human immunodeficiency virus (HIV-1) is associated with downregulation of the CD4 receptor and resistance to further HIV-1 infection, the phenomenon of viral interference. The ACH2 cell line, a model for chronic HIV-1 infection, possesses a single integrated copy of the HIV-1 strain LAI, is essentially CD4 negative, and can be induced to make virus by a variety of stimuli. We utilized the known sequence differences between HIVLAI and HIVRF to devise a polymerase chain reaction (PCR) strategy that permits reliable and quantitative discrimination between the two strains. We demonstrate that ACH2 cells can be superinfected by HIVRF at a frequency of 60-300 HIVRF genomes/10(4) ACH2 cells and that the frequency of superinfection appears to increase with time. Reverse transcription of ACH2 mRNA from days 13, 27, and 38 postinfection allowed a similar PCR strategy (RT-PCR) to be used to analyze full-length HIVRF- and HIVLAI-specific transcripts. These data suggested that superinfection of ACH2 with HIVRF results in an increase in expression of both HIVRF and HIVLAI mRNA. From day 13 to day 38 postinfection there was an increase in the relative expression of HIVRF compared with HIVLAI. By day 38, when only 1.1% of HIV DNA sequences were HIVRF derived, roughly 80% of the HIV-specific full-length mRNA was HIVRF in origin, with a concomitant decrease in HIVLAI transcription.
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PMID:Consequences of human immunodeficiency virus type 1 superinfection of chronically infected cells. 750 36

Infection by HIV-1 of monocyte cell lines, in contrast to T lymphocytes, did not lead to decreased steady-state levels of CD4 mRNA. Similar results were also obtained using clonal derivatives of infected U-937 cells that produced either competent, highly replicative progeny viruses or defective non-infectious particles. In each case, the infected U-937 cells or clonal derivatives were found to be significantly deficient with regard to surface representation of CD4 protein, in spite of the presence of high levels of CD4 mRNA. However, both HIV-1-infected U-937 cells, as well as clonal derivatives which produced high levels of viral env mRNA and non-infectious viral structures that lacked envelope glycoproteins, contained diminished levels of OKT4-immunoprecipitable CD4 protein, in comparison with uninfected U-937 cells. Thus, expression of viral env mRNA but neither the efficient synthesis or packaging of viral glycoproteins or viral assembly is required for disappearance of cell surface CD4 to occur. Furthermore, viral gp160 co-precipitated with CD4 in both the parental and cloned cell lines. We have also shown that the generation of intracellular complexes of gp160 and CD4 is directly responsible for the disappearance of cell surface CD4 in HIV-1-infected U-937 cells. In this system, expression of gp160 was both necessary and sufficient to result in CD4 receptor down-modulation. Finally, in vitro co-translation studies revealed that the presence or synthesis of viral gp160 led to a failure to efficiently generate CD4 protein.
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PMID:The role and fate of the CD4 molecule in lymphocytes and monocytes infected by HIV-1. 750 65

In this study, we evaluated the effect of a short-term exposure (2 hours) to two different lymphocytotropic strains of human immunodeficiency virus type 1 (HIV-1; HIVIIIB and ICR-3) on the survival of a factor-dependent CD34+ hematopoietic progenitor cell line (TF-1). At flow cytometry analysis, a significant (P < .05) increase in the frequency of apoptotic cell death was observed in HIV-1-treated TF-1 cells, supplemented with low doses of either interleukin-3 (IL-3; 0.02 to 1 ng/mL) or granulocyte-macrophage colony-stimulating factor (GM-CSF; 0.02 to 0.2 ng/mL) with respect to mock-treated cells. On the other hand, higher doses of both cytokines or combinations of suboptimal concentrations of IL-3 plus GM-CSF (eg, 0.2, plus 0.2 ng/mL) completely reversed the HIV-1-induced increase of apoptosis. Remarkably, no signs of productive or latent virus replication were ever observed in HIV-1-treated TF-1 cells up to 16 days of liquid culture. In parallel experiments, the in vitro exposure to HIVIIIB induced a significant and progressive increase of apoptotic death in purified bone marrow CD34+ cells, seeded in liquid cultures in the presence of 1 ng/mL IL-3. The HIV-1-induced apoptosis of TF-1 cells was likely triggered by the simple interaction of HIV-1 envelope glycoprotein gp120 with CD4 receptor, which was expressed at a low level on the surface of TF-1 cells. In fact, treatment of TF-1 cells with recombinant gp120 plus a polyclonal anti-gp120 antibody or with anti-CD4 monoclonal antibody plus rabbit antimouse IgG significantly increased the percentage of apoptotic death. These data suggest that HIV-1, and perhaps also free gp120 in the presence of anti-gp120 antibody; could play a direct role in the pathogenesis of peripheral blood cytopenias in acquired immunodeficiency syndrome patients by inducing apoptotic death of hematopoietic progenitor cells without the need of a direct infection.
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PMID:In vitro exposure to human immunodeficiency virus type 1 induces apoptotic cell death of the factor-dependent TF-1 hematopoietic cell line. 750 78

We have examined for synergy between the IIIB strain of HIV-1 and Epstein-Barr virus (EBV) during infection of a homogeneous cell type. In order to obtain a cell population consisting of a homogeneous cell type, CD19-positive B lymphocytes were purified from human tonsils by flow cytometry. CD19-positive lymphocytes did not express detectable surface CD4 antigen. However, CD4 mRNA could be detected in CD19-positive lymphocytes by reverse transcription coupled to polymerase chain reaction and by dot blot hybridization using an antisense riboprobe. Transcription of CD4 mRNA in CD19-positive lymphocytes was suppressed by infection with the B95-8 strain of EBV and lost in B95-8-transformed lymphoblastoid cell lines. In contrast, the P3HR-1K strain of EBV had no effect on the level of CD4 mRNA. HIV-1 could infect CD19-sorted B cells as measured by accumulation of reverse transcriptase and syncytia induction after coculture with SupT1 cells. HIV-1 infection of CD19-bearing lymphocytes was blocked by OKT4a antibodies. The ability of HIV-1 to replicate in CD19-positive B lymphocytes declined following preinfection with B95-8 but not with P3HR-1K. These results as well as results with an EBNA-2 expression vector suggest that down-regulation of both CD4 mRNA and HIV-1 infection in human B cells is a function of EBV nuclear antigen EBNA-2. The fact that native CD19-positive B lymphocytes express sufficient CD4 receptor mRNA to allow HIV-1 infection strengthens the possibility that HIV-1 replication in B cells directly participates in AIDS pathogenesis. In addition, infection with EBV may modulate the ability of HIV-1 to infect and establish a latent infection in B lymphocytes in co-infected individuals.
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PMID:CD4 mRNA expression in CD19-positive B cells and its suppression by the Epstein-Barr virus. 750 84

Reverse transcription of the HIV RNA genome is thought to occur in the host cell cytoplasm after viral adsorption. However, viral DNA has been isolated in cell-free virus particles. We have quantitated by polymerase chain reaction (PCR) amplification the amount of viral DNA in virions as compared to RNA. Virus produced by proviral DNA transfections of cos-7 cells or by chronically-infected H9 cells; neither of which express the cell surface CD4 receptor, contained at least 1000 times more viral RNA than DNA. In contrast, only 60 times more RNA than DNA was present in virus particles produced by transfection of Jurkat cells, which were CD4-positive and thus potentially susceptible to superinfection. Protease-defective virus, carrying only the precursor of reverse transcriptase (RT) p160gag-pol, contained virtually no detectable DNA. These results indicate that only mature RT (p66/p51) and not its precursor (p160gag-pol) is responsible for the presence of viral DNA in HIV.
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PMID:Mature reverse transcriptase (p66/p51) is responsible for low levels of viral DNA found in human immunodeficiency virus type 1 (HIV-1). 751 79


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