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

In studies on viral interference, cloned T-cell lines chronically infected with human immunodeficiency virus (HIV) type 1 or HIV-2 were inoculated with several strains of these two AIDS retrovirus subtypes. HIV-2UC1-infected cells, which still express the CD4 receptor, could be superinfected with a variety of HIV-1 and HIV-2 strains. This event was accompanied by cytopathic effects in the cells and production of pseudotype virions with an expanded cellular host range. HIV-1- or HIV-2-infected clonal cell lines, which did not express CD4, could not be superinfected by any HIV strains but were coinfected after transfection of molecular clones into the persistently infected cells. These observations indicate that viral interference with HIV occurs at the cell surface and involves a down-modulation of the CD4 molecule. If the CD4 protein is expressed, superinfection can take place, and phenotypically mixed virus particles are produced. Since HIV-1 and HIV-2 dually infected individuals have been detected, these in vitro observations may have relevance to the in vivo state.
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PMID:Human immunodeficiency virus (HIV) type 1 can superinfect HIV-2-infected cells: pseudotype virions produced with expanded cellular host range. 134 69

The first step in infection of human mononuclear cells with HIV involves the high affinity binding of the viral envelope glycoprotein, gp120, to the cell-surface receptor, CD4. To gain a better understanding of the molecular basis of this interaction, we have analyzed the ability of gp120 to bind to a panel of 40 mutant CD4 proteins containing single or double amino acid substitutions. In addition, the binding of several anti-CD4 mAb to the mutant CD4 proteins was measured. These mAb were chosen on the basis of the previous demonstration that they bind to epitopes in CD4 adjacent to the gp120-binding site. This analysis permits discrimination between mutations that probably cause localized conformational changes and those that alter residues likely to make direct contact with gp120 and with the mAb. Our results indicate that gp120 from two different strains of HIV binds to a larger region of the CD4 protein than previously described. The data has also been used to map the epitopes of mAb previously identified as anti-idiotype vaccine candidates. The results have important implications for the development of CD4-based therapies for AIDS.
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PMID:Analysis of the site in CD4 that binds to the HIV envelope glycoprotein. 169 Dec 26

We used a bifunctional reagent for the design of a new therapeutic agent constructed by cross-linking a soluble form of the CD4 protein to red blood cell membranes. CD4 is a member of the immunoglobulin gene superfamily and is the receptor for the AIDS virus, HIV. We produced soluble CD4 in eucaryotic cells transfected with a soluble CD4 expression vector, and purified it by cation-exchange chromatography. Flow cytometry studies demonstrated that CD4-coated red blood cells were specifically stained with an anti-CD4 monoclonal antibody, whereas intact red blood cells and intermediates obtained during the coupling procedure were not stained. By comparison, with CD4+ lymphoid cells, the number of soluble CD4 molecules per CD4-expressing red blood cells was estimated to be approx. 100,000. We present evidence that, unlike the classical chromium chloride coupling method, large amounts of soluble CD4 were efficiently and uniformly coupled to RBCs. CD4 red blood cells bind specifically HIV particles, and inhibit the binding of HIV particles to target cells, the initial step of HIV life cycle. The anti-HIV activity of CD4-bearing red blood cells was found to be at least 20-times higher than that of free soluble CD4. Our results demonstrate that proteins can be efficiently coupled to red blood cells using bifunctional reagents. They also suggest that CD4-coated RBC are promising CD4-based anti-HIV agents.
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PMID:Functional expression of the CD4 protein after cross-linking to red blood cells with a bifunctional reagent. 199 7

A decline in the T-cell population usually marks the onset of progressive immunological disease in individuals infected with the human immunodeficiency virus (HIV). Because CD4+ cells help to coordinate efficient immune responses, some of the defects in the immune function in advanced cases of AIDS may be explained by the disappearance of these cells. Therefore, an understanding of the mechanisms used by HIV to induce the reduction of CD4+ cells is important. Here we use a Moloney murine leukaemia virus-based retroviral vector in order to express the nef gene of HIV-1 in three lymphocytic cell lines expressing CD4. In all cases we find that cell-surface CD4 expression is inversely related to nef expression. However, nef does not alter steady-state levels of CD4 RNA or CD4 protein. Also, nef can downregulate a CD4 triple mutant (Ser----Ala) that is neither phosphorylated nor down-regulated by phorbol esters, indicating that nef is acting by a different mechanism.
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PMID:Serine phosphorylation-independent downregulation of cell-surface CD4 by nef. 201 52

Studies evaluating cell fusion by HIV indicate that optimal conditions for measuring this biological process involve the use of appropriate numbers of cells, the expression of HIV gp120 in infected cells, the presence of the CD4 protein on the surface of uninfected cells, and sugar moieties. Cellular metabolism and nucleic acid synthesis as measured by DNA, RNA and protein synthesis are not requires. Proteolytic enzymes eliminate virus fusion only when the uninfected cells involved in the process are treated. Since the CD4 protein remains on the surface of the treated cells, the structure of this receptor must be changed sufficiently so that it cannot participate in the fusion process. Alternatively, the results may indicate the elimination by trypsin of a specific fusion receptor.
AIDS 1990 May
PMID:Parameters involved in the cell fusion induced by HIV. 219 7

The human immunodeficiency virus type 1 (HIV-1) uses the CD4 protein as a receptor for infection of susceptible cells. A candidate structure for the HIV-1 binding site on the CD4 protein was identified by epitope mapping with a family of eight functionally distinct CD4-specific monoclonal antibodies in conjunction with a panel of large CD4-derived synthetic peptides. All of the seven epitopes that were located reside within two immunoglobulin-like disulfide loops situated between residues 1 and 168 of the CD4 protein. The CD4-specific monoclonal antibody OKT4A, a potent inhibitor of HIV-1 binding, recognized a site between residues 32 and 47 on the CD4 protein. By analogy to other members of the immunoglobulin superfamily of proteins, this particular region has been predicted to exist as a protruding loop. A synthetic analog of this loop (residues 25 to 58) showed a concentration-dependent inhibition of HIV-1-induced cell fusion. It is proposed that a loop extending from residues 37 to 53 of the CD4 protein is a binding site for the AIDS virus.
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PMID:Location and chemical synthesis of a binding site for HIV-1 on the CD4 protein. 245 25

The soluble form of human CD4, an HIV receptor molecule first detected on the surface of T cells, binds glycoprotein gp120, a coat protein of human immunodeficiency virus, and has potential value for the treatment of AIDS. As a first step toward providing the necessary quantities of this protein at an affordable price we report here on the production of functional, soluble human CD4 in transgenic mice. In these animals, a regulatory region derived from a murine gene encoding the whey acidic protein directs synthesis of human CD4 protein to the mammary gland of lactating animals where it is secreted into milk.
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PMID:Functional human CD4 protein produced in milk of transgenic mice. 248 19

Early events of HIV infection of the CNS are not yet clear. HIV infection in most recent cases, generally shows a prolonged interval between diagnosis and death. HIV infection, months to years before the patient's death, may or may not result in early neurologic symptoms. AIDS patients with spinal cord symptoms often show a sudden onset of long tract signs and a temporally related altered mental status indicating the appearance of both myelitis and encephalitis. Immunohistochemical localization of the HIV cell-surface receptor protein, CD4, and of HIV antigens in cerebral and lymph node venular endothelial cells suggests that a natural occurrence or induction of CD4 protein in some endothelial cells allows transmission of HIV from circulating infected white blood cells preferentially to certain tissues through endothelial cell infection. HIV immunolocalization is present in perivascular astrocytes, particularly in long white matter tracts, and on the surface of oligodendrocytes. HIV immunoreactivity is mostly in macrophages and multinucleated cells in a typical autopsy case, but this may be due to the clearing of HIV antigen from early sites of infection by the hematogenous cells. Not all immunoreactivity for HIV antigens is necessarily due to HIV gene products. Cross reacting epitopes, such as that of HIV envelope glycoprotein gp120 and neuroleukin, may be "seen" not only by antibodies on tissue sections, but by an AIDS patient's immune system, thus targeting a CNS antigen for immune-complex formation. Evidence for hypersensitivity disease in the CNS in AIDS includes the frequent findings of demyelination, perivenous chronic inflammation, chronic vasculitis, and perivenous hemorrhages. The white matter demyelination so frequently reported in all areas of the CNS in AIDS could be the result of a combination of factors that include direct HIV vasculitis, opportunistic infections, and hypersensitivity responses. The blood-brain barrier is breached when immune-related antigens interact on CNS vascular endothelial cells. Perhaps the CD4 antigen, which responds to interaction with antigen-presenting cells and enhances cellular immune activity, is induced or increased in the CNS in association with immune activity and in the presence of a leaky blood-brain barrier. Therefore, with or without HIV in the CNS, hypersensitivity disease, including demyelination, may be the result of long-standing activity of the immune system in AIDS patients.
Prog AIDS Pathol 1989
PMID:Immunohistochemistry of human immunodeficiency virus in the central nervous system and an hypothesis concerning the pathogenesis of AIDS meningoencephalomyelitis. 249 Dec 41

Human immunodeficiency virus type 1 (HIV-1) selectively infects cells expressing the CD4 molecule, resulting in substantial quantitative and qualitative defects in CD4+ T lymphocyte function in patients with acquired immunodeficiency syndrome (AIDS). However, only a very small number of cells in the peripheral blood of HIV-1-infected individuals are expressing virus at any given time. Previous studies have demonstrated that in vitro infection of CD4+ T cells with HIV-1 results in downregulation of CD4 expression such that CD4 protein is no longer detectable on the surface of the infected cells. In the present study, highly purified subpopulations of peripheral blood mononuclear cells (PBMCs) from AIDS patients were obtained and purified by fluorescence-automated cell sorting. They were examined with the methodologies of virus isolation by limiting dilution analysis, in situ hybridization, immunofluorescence, and gene amplification. Within PBMCs, HIV-1 was expressed in vivo predominantly in the T cell subpopulation which, in contrast to the in vitro observations, continued to express CD4. The precursor frequency of these HIV-1-expressing cells was about 1/1000 CD4+ T cells. The CD4+ T cell population contained HIV-1 DNA in all HIV-1-infected individuals studied and the frequency in AIDS patients was at least 1/100 cells. This high level of infection may be the primary cause for the progressive decline in number and function of CD4+ T cells in patients with AIDS.
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PMID:The reservoir for HIV-1 in human peripheral blood is a T cell that maintains expression of CD4. 266 81

Antibodies that enhance human immunodeficiency virus (HIV) infectivity have been found in the blood of infected individuals and in infected or immunized animals. These findings raise serious concern for the development of a safe vaccine against acquired immunodeficiency syndrome. To address the in vivo relevance and mechanism of this phenomenon, antibody-dependent enhancement of HIV infectivity in peripheral blood macrophages, lymphocytes, and human fibroblastoid cells was studied. Neither Leu3a, a monoclonal antibody directed against the CD4 receptor, nor soluble recombinant CD4 even at high concentrations prevented this enhancement. The addition of monoclonal antibody to the Fc receptor III (anti-FcRIII), but not of antibodies that react with FcRI or FcRII, inhibited HIV type 1 and HIV type 2 enhancement in peripheral blood macrophages. Although enhancement of HIV infection in CD4+ lymphocytes could not be blocked by anti-FcRIII, it was inhibited by the addition of human immunoglobulin G aggregates. The results indicate that the FcRIII receptor on human macrophages and possibly another Fc receptor on human CD4+ lymphocytes mediate antibody-dependent enhancement of HIV infectivity and that this phenomenon proceeds through a mechanism independent of the CD4 protein.
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PMID:The Fc and not CD4 receptor mediates antibody enhancement of HIV infection in human cells. 278 47


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