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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CD4 molecule is functionally involved in the class II MHC-restricted T cell response to Ag. CD4 is also the receptor for HIV-1, the major etiologic agent of AIDS. We have assessed whether the interaction of the HIV-1 envelope protein with the CD4 molecule might interfere with the normal function of CD4, thereby contributing to the immunosuppression observed after HIV infection. Using a murine T cell hybridoma which expresses the human CD4 protein and exhibits a CD4-dependent response to Ag, we demonstrate that the HIV envelope protein gp120 can specifically inhibit this response.
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PMID:Inhibition of CD4+ T cell function by the HIV envelope protein, gp120. 284 91

Human immunodeficiency virus (HIV), the causative agent of AIDS, infects human lymphocytes and monocytes. An interaction between the viral envelope gp 120 and CD4 protein is required to initiate an infectious cycle. HIV infection in vitro induces syncytium formation by cell-to-cell fusion; this aspect of viral cytopathogenicity is even more dependent on gp120-CD4 interactions. That gp120 is extremely heavily glycosylated (31-36 N-linked glycans per molecule), suggests involvement of N-linked glycans in the gp120-CD4 interaction. We therefore investigated the effects of castanospermine, 1-deoxynojirimycin (dNM) and 1-deoxymannojirimycin (dMM), three trimming glycosidase inhibitors which perturb N-linked glycan structure, on induction of the formation of syncytium between HIV-infected and CD4-expressing cells. The glucosidase inhibitors castanospermine and dNM, but not the mannosidase inhibitor dMM, inhibited syncytium formation and interfered with infectivity. The potential of glucosidase inhibitors as anti-HIV therapeutic agents deserves further investigation, especially because dNM and related compounds show little toxicity in vitro and in vivo.
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PMID:Interference with HIV-induced syncytium formation and viral infectivity by inhibitors of trimming glucosidase. 295 66

CD4 (T4) is a glycoprotein of relative molecular mass 55,000 (Mr 55K) on the surface of T lymphocytes which is thought to interact with class II MHC (major histocompatibility complex) molecules, mediating efficient association of helper T cells with antigen-bearing targets. The CD4 protein is also the receptor for HIV, a T-lymphotropic RNA virus responsible for the human acquired immune deficiency syndrome (AIDS) (refs 4-7). To define the mechanisms of interaction of CD4 with the surface of antigen-presenting cells and with HIV, we have isolated the CD4 gene and expressed this gene in several different cellular environments. Here we describe an efficient expression system in which a recombinant, soluble form of CD4 (sCD4) is secreted into tissue culture supernatants. This sCD4 retains the structural and biological properties of CD4 on the cell surface, binds to the envelope glycoprotein (gp110) of HIV and inhibits the binding of virus to CD4+ lymphocytes, resulting in a striking inhibition of virus infectivity.
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PMID:A soluble form of CD4 (T4) protein inhibits AIDS virus infection. 325 44

We have previously demonstrated that recombinant soluble CD4 protein (rsT4) blocks both HIV-1 infection of CD4 bearing lymphocytes and syncytium formation in vitro. (Recombinant soluble CD4 is designated by rsT4). Hence, we suggested the use of rsT4 in therapy for AIDS or the prevention of HIV-1 infection in individuals with a known risk of exposure. However, concerns arose that rsT4 might be immunosuppressive because of its implicated role in the enhancement of certain lymphocyte activation events through its engagement of MHC class II molecules on target cells. We therefore assessed the effect of recombinant soluble CD4 upon a number of functional and activation parameters of lymphocytes, including cellular proliferation, IL-2 secretion, and cytolytic capability, after antigenic or mitogenic stimulation. We report here that rsT4, at 60-fold over the concentration needed to block acute HIV-1 infection in vitro, does not significantly inhibit the activation of human peripheral blood lymphocytes by either PHA, tetanus toxoid or allogeneic cells. These results indicate that rsT4 will potentially exert minimal immunosuppressive effects in vivo, thus supporting the feasibility of clinical trials of rsT4 in the treatment or prevention of AIDS. In addition, the implications of these results for the interactions between CD4 and MHC class II molecules during lymphocyte activation are discussed.
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PMID:Effect of recombinant soluble CD4 on human peripheral blood lymphocyte responses in vitro. 326 92

Lymphocytotoxic autoimmunity (LA) is ubiquitous in AIDS. Its causes are unknown. We report that significant amino acid sequence similarities exist between the proteins of infectious organisms associated with AIDS and the CD4 protein of T-helper lymphocytes. These included: HIV, cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex viruses (HSV), Varicella Zoster virus (VZV), Escherichia coli, Mycobacteria, Mycoplasmas, Plasmodium, and Staphylococcus. It has been reported previously that HIV proteins have significant similarities with human class II MHC (HLA class II) proteins. Since CD4 and HLA class II proteins are chemically complementary, pairs of homologous antigens will also be complementary. It follows that concurrent infections with CD4 and HLA class II-homologous antigens will result in idiotype-antiidiotype antibody pairs that cannot distinguish 'self' from 'nonself', that acts as lymphocytotoxins, and form circulating immune complexes. Thus, combined HIV-CMV, HIV-EBV, HIV-HBV, HIV-mycoplasma, or other appropriate infectious pairs may suffice to trigger LA in AIDS.
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PMID:CD4 similarity to proteins of infectious agents in AIDS and their role in autoimmunity. 773 8

More than 90% of people with AIDS develop circulating immune complexes (CICs) and lymphocytotoxic antibodies (LCTAs). Animals infected with HIV, however, never display CICs or LCTAs, and remain healthy. Similarly, HIV-infected people who do not develop CICs or LCTAs also do not progress to AIDS. The appearance of CICs and LCTAs is, however, highly prognostic for AIDS and death. Since HIV infection does not, per se, lead to the development of CICs and LCTAs, other causes are likely. One such cause, for which both epidemiologic and experimental evidence exists, is semen. Semen components include sperm, seminal fluid, lymphocytes, and sometimes infectious agents, including HIV, mycoplasmas, and herpes and hepatitis viruses, all of which independently cause immune suppression. Extensive evidence demonstrates sperm (and various viruses) contains many proteins mimicking the CD4 protein of T-helper cells, while HIV, mycoplasmas, and seminal fluid mimic class II MHC proteins of other lymphocytes. We identify a large number of protein sequences that display such mimicry using computer homology searching, and demonstrate experimentally that sperm antibodies specifically precipitate antibodies against class II MHC mimics such as mycoplasmas, which in turn precipitate antibodies to lymphocyte antigens. These data prove that immunologic exposure to sperm and lymphocytes (as may occur in receptive anal intercourse, needle sharing, or blood transfusions) is theoretically capable of initiating lymphocytotoxic autoimmunity. Such autoimmunity may play a significant role in the pathogenesis of AIDS, and will need to be addressed clinically in high risk individuals regardless of HIV status and regardless of the success of anti-HIV prophylaxis and treatment.
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PMID:Semen alloantigens and lymphocytotoxic antibodies in AIDS and ICL. 774 57

HIV is the etiologic agent of AIDS. AIDS results from the loss of cells that are central to immune responses, T lymphocytes that express the CD4 protein on their surface. This paper relates HIV structure and replication to the clinical course of HIV infection. The virology of HIV replication is discussed first at the cellular and molecular levels. The course of HIV infection in vivo then is discussed and related to HIV replication. Finally, models that have been proposed to explain the mechanism whereby HIV causes immunodeficiency are considered. Although much is known about the growth of the virus both in vitro and in vivo, many questions remain about how HIV can deplete CD4-positive T lymphocytes and cause AIDS.
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PMID:HIV: virology and mechanisms of disease. 791 89

HCN-1A is a human cerebral cortical neuronal cell line having properties consistent with cells of immature neuronal origin. This article details evidence for productive low-level infection of HCN-1A cells with human immunodeficiency virus type 1 (HIV-1). In vitro exposure to HCN-1A monolayers to a high titer of either LAV/HTLV-IIIB or HTLV-IIIMN resulted in HIV-1 p24 antigen production and a moderate increase in reverse transcriptase activity in cell-free supernatants. The cells in both LAV/HTLV-IIIB- and HTLV-IIIMN-infected cultures were passaged and proliferated as long as 5 weeks while continuing to express low levels of viral antigen. Virus-positive cells were detected by indirect immunofluorescence, using serum from an individual with acquired immune deficiency syndrome (AIDS) as well as with a gp120 monoclonal antibody. Confirmation of HCN-1A infection was provided by polymerase chain reaction analyses of both nuclear and cytoplasmic DNA and by de novo synthesis of viral proteins as shown by metabolic labeling and immunoprecipitation. Virus in cell-free supernatants from infected HCN-1A cultures was passaged to a permissive human T cell line (A3.01). HCN-1A cells had no detectable surface CD4 protein or CD4 message. However, the cells expressed the membrane glycolipids, galactocerebroside and sulfatide, possible receptors for gp120 on cells of neuronal origin. Undifferentiated HCN-1A cells provide an in vitro model for investigating potential interactions of HIV-1 with a homogeneous population of immature cortical neurons.
AIDS Res Hum Retroviruses 1993 May
PMID:Human cortical neuronal cell line: a model for HIV-1 infection in an immature neuronal system. 831 71

Characteristics of human immunodeficiency virus (HIV) strains and the host immune response against the virus are major determinants in the pathogenesis of AIDS. HIV isolates can be distinguished by their ability to infect and replicate to high titers in cells, to kill those cells, and to down-modulate the CD4 protein on the cell surface. In addition, their sensitivity to serum neutralization or enhancement of infection can be appreciated. The genetic sequences associated with these biologic and serologic properties have been localized and could eventually be helpful for antiviral therapy. These variations in properties of HIV strains appear to correlate with induction of neurologic and gastrointestinal disease by certain strains. In some cases, HIV can establish a silent, latent infection. The mechanisms involved are not well defined, but one concept involves the nef gene, which with some strains, can suppress virus replication. An important finding is that viruses recovered from individuals as they advance to disease have many properties in vitro of presumed virulence in the host, such as a wide cellular host range, cytopathicity, and resistance to the antiviral effect of Nef. The host immune response can control virus spread through antiviral antibodies or cellular immune responses. Neutralizing antibodies are not commonly found in infected individuals, suggesting that viruses "escape" this immune response. Instead, in some symptomatic patients, antibodies that enhance virus infection can be detected. The difference in sensitivity of a virus appears related to its envelope proteins. Cellular immune responses offer some promise in maintaining or eliminating virus infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Features of human immunodeficiency virus infection and disease. 843 77

A retroviral vector was constructed in which a gene encoding a mutated soluble CD4 protein that is retained in the endoplasmic reticulum (sCD4-KDEL) is expressed under control of human immunodeficiency virus type 1 (HIV-1) regulatory elements. HIV-1 infection of a human T-cell line transduced with this vector led to induction of sCD4-KDEL synthesis and a block in transport of the HIV envelope protein to the cell surface. There was a complete block to maturation of infectious HIV-1 in the transduced cells, no viral spread, and little or no syncytium formation. Infected cells gradually disappeared from the culture over a period of 2 months. This intracellular trap for HIV has potential application in gene therapy for AIDS.
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PMID:Blockade of human immunodeficiency virus type 1 production in CD4+ T cells by an intracellular CD4 expressed under control of the viral long terminal repeat. 846 77


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