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

The processing and secretion of the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) were studied in chronically infected T cells and in primary macrophages treated with an antiviral antibiotic brefeldin A (BFA). BFA blocks the egress of proteins from the endoplasmic reticulum and has a profound effect on the structure of cis/medial Golgi. In MOLT-3 cells infected with the IIIB strain of HIV-1 (MOLT-3/IIIB), BFA inhibited the intracellular processing of gp160. The secretion of envelope proteins from these cells was significantly inhibited in the presence of BFA. The gag proteins, on the other hand, were processed and secreted normally. BFA also inhibited the proteolytic processing of gp160 in primary macrophages infected with HIV-1. The infectivity of virus pelleted from the medium of MOLT-3/IIIB cells treated with BFA was markedly lower than that obtained from untreated cells. These results demonstrate that the proteolytic processing of gp160 in HIV-1-infected cells takes place after the glycoprotein exists the endoplasmic reticulum and that the transport of glycoprotein to the cell surface is required for assembly of complete HIV-1 particles.
AIDS Res Hum Retroviruses 1991 Aug
PMID:Brefeldin A inhibits the processing and secretion of envelope glycoproteins of human immunodeficiency virus type 1. 171 46

A panel of human monoclonal antibody Fab fragments has been generated against the surface glycoprotein gp120 of type 1 human immunodeficiency virus (HIV) by antigen selection from a random combinatorial library expressed on the surface of filamentous phage. The library was prepared from 5 ml of bone marrow from an asymptomatic individual who has been HIV-positive for 6 years. The antibodies have high affinity for antigen (mostly with affinity constants of greater than 10(8) M-1) and notable sequence diversity. Given appropriate donor selection, the methods described should allow the generation of antibodies for the evaluation of passive immunization as a therapy for AIDS.
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PMID:A large array of human monoclonal antibodies to type 1 human immunodeficiency virus from combinatorial libraries of asymptomatic seropositive individuals. 171 45

The principal neutralizing determinant of the human immunodeficiency virus type 1 (HIV-1) is located within the V3 loop of the surface glycoprotein gp120. Recently a mutational approach was used to demonstrate that the tip of the V3 loop is involved in cell fusion mediated by the HIV-1 envelope glycoproteins. Here these results are extended by introducing seven additional single amino acid mutations in the V3 loop. Mutations at highly conserved amino acids in the left stem, tip, and right stem of the V3 loop blocked or greatly reduced cell fusion without affecting envelope glycoprotein processing, transport, or binding to the CD4 receptor molecule. This study further characterizes the involvement of the V3 loop in cell fusion mediated by the HIV-1 envelope glycoproteins and identifies residues involved in the fusion reaction.
AIDS Res Hum Retroviruses 1991 Oct
PMID:Identification of conserved residues in the human immunodeficiency virus type 1 principal neutralizing determinant that are involved in fusion. 172 Jun 27

The significance of the human immunodeficiency virus (HIV) in the small intestinal lamina propria in patients with the acquired immune deficiency syndrome or conditions related to that syndrome who have chronic diarrhea and malabsorption is unclear. To investigate this issue, upper endoscopy (after a 12- to 16-hour fast) with duodenal biopsy and aspirate was performed in 20 HIV-infected seropositive homosexual men referred for diarrhea of more than 8 weeks duration (Group 2) and in 9 HIV-infected homosexual men referred for dysphagia or dyspepsia with no symptoms of malabsorption (Group 1). All biopsy specimens were examined by light microscopy and immunochemical staining with monoclonal antibody against HIV glycoprotein gp41. Electron microscopy was performed in 18 patients in Group 2 and in all patients in Group 1. Immunogold electron microscopy was used as a confirmatory test for identified HIV particles. In addition, D-xylose absorption was measured in all patients after a 25-g dose of D-xylose with measurement of serum D-xylose concentration 1 hour after the dose and measurement of 5-hour urinary D-xylose excretion. Mean serum D-xylose was 35.4 +/- 4.5 mg/dL in Group 1 and 15.8 +/- 2.3 mg/dL in Group 2 (P less than 0.001), whereas mean urine D-xylose was 5.5 +/- 0.6 g in Group 1 and 2.0 +/- 0.4 g in Group 2 (P less than 0.001). Immunoperoxidase for gp41 was positive in 5 (56%) patients in Group 1 and in 12 (60%) patients in Group 2. Lamina propria HIV viral particles were identified by electron microscopy in both patient groups. Viral particles were seen within and adjacent to the cytoplasm of mononuclear cells and were not present in enterocytes or neuroendocrine cells. There were no significant differences in serum or urine D-xylose tests between patients with and without lamina propria HIV. In addition, lipid accumulation in intercellular spaces near the basolateral membrane of adjacent enterocytes was seen in 33% of patients with chronic diarrhea. These findings suggest that lamina propria HIV is not a direct cause of enteropathy in HIV-infected patients and that lymphatic obstruction may be one pathophysiologic mechanism producing this malabsorptive state.
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PMID:Histopathologic findings of duodenal biopsy specimens in HIV-infected patients with and without diarrhea and malabsorption. 141 28

The aim of this study was to determine whether mannosyl-specific lectins, especially Concanavalin A (ConA), may bridge HIV-1 env glycoproteins to cell membranes to increase virus binding to its targets, and to what extent this lectin-carbohydrate interaction can modify HIV-1 infectivity for monocytic compared with lymphoid cells. Monocytic U937 and lymphoid CEM cells, which both express surface mannose, were utilized. Whether first incubated with env glycoprotein or with the cells, lectins bound both to the cells and to radiolabeled recombinant gp160 (rgp160). Thus, they enhanced rgp160 adsorption to the cells in a methyl-alpha-mannose inhibitable manner. ConA did not appear to bind to the V1 domain of CD4 at the U937 cell surface since Leu3a binding was not blocked in the presence of ConA, nor was recombinant CD4 retained on a ConA-agarose affinity matrix. Moreover, enhanced rgp160 binding to the cells was CD4 independent, since it was not modified by preincubating the cells with Leu3a. Finally, ConA did not inhibit the binding of CD4-IgG3 chimeric molecules to virions immobilized on nitrocellulose membrane, which argues against the possibility that it interferes with the interaction of gp120 and CD4. However, both when incubated with the virus or with the cells and despite mediating enhanced binding of env glycoprotein, ConA neutralized HIV-1 infectivity for monocytic U937 as well as for lymphoid CEM cells. In this respect, ConA behaves like neutralizing antibodies which do not interfere with CD4 binding of gp120 but rather with some later event that leads to virus entry. These findings obtained with plant lectins may be of relevance in vivo, inasmuch as endogenous mannosyl-binding proteins, which are known to function as opsonins, have been reported to inhibit in vitro infection by HIV-1.
AIDS Res Hum Retroviruses 1992 Jan
PMID:Lectin-carbohydrate interactions and infectivity of human immunodeficiency virus type 1 (HIV-1). 173 38

Acquired immune deficiency syndrome (AIDS) is caused by infection with the human immunodeficiency virus (HIV), a human retrovirus. The virus infects cells of the immune system by attachment of a glycoprotein viral envelope (gp 120) to a molecule expressed on human helper T cells called CD4. The fusion of the virus envelope protein to its specific receptor allows HIV to penetrate the T cell. Once inside the cell viral RNA is transcribed into double-stranded DNA by an enzyme unique to retroviruses, reverse transcriptase. The double-stranded, proviral DNA travels to the nucleus of the cell and is integrated into the infected cell's chromosomal DNA where it may remain latent for years. As a result of triggers that are poorly understood, viral replication becomes activated and proviral DNA is transcribed back into genomic RNA and RNA that is translated into viral proteins, both of which are packaged and bud from the infected T cell as infectious virus. The viral life cycle orchestrates the natural history of clinical HIV infection. Three to four weeks following exposure to HIV there is a phase of rapid viral replication, high levels of plasma viremia, and development of a "flue like" illness. Four to six weeks after exposure, during this stage of acute infection, antibodies to HIV core (p24) and envelope (gp 160, gp 120, gp41) proteins appear. Six to eight weeks after exposure symptoms disappear and plasma viremia subsides, presumably due to clearance by the immune system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathogenesis and natural history of HIV infection. 175 33

Retroviral envelope glycoproteins interact with cell receptors and are targets for antiviral immune responses in infected hosts. Macaque simian immunodeficiency virus (SIVmac) is a T-lymphocytopathic lentivirus which causes an AIDS-like disease in rhesus macaques. The envelope gene of SIVmac encodes a precursor glycoprotein (gp160) which is cleaved into an external domain (gp130) and a transmembrane domain (gp32). To investigate the functional and immunological properties of the SIV external envelope glycoprotein, we have used genetically engineered mammalian cells to produce recombinant gp130 (rgp130). The rgp130 has the appropriate molecular weight, is glycosylated, and has native conformation as determined by binding to the cell receptor for SIV, the CD4 antigen. Rhesus macaques immunized with purified rgp130 formulated in muramyl dipeptide adjuvant generated high titers of antienvelope antibodies. Antibodies from these macaques were tested for in vitro virus neutralization; very low or undetectable levels of neutralization were observed. In contrast, neutralizing antibodies were readily detected in sera from goats immunized with rgp130. With respect to cell-mediated immunity, proliferative responses to rgp130 were demonstrated in peripheral blood monocyte cells (PBMC) from macaques immunized with the recombinant glycoprotein as well as in PBMC from SIV-infected animals. These results show that rgp130 is functional and immunogenic; the potential of rgp130 for protective immunization remains to be determined.
AIDS Res Hum Retroviruses 1991 Nov
PMID:Functional and immunological characterization of SIV envelope glycoprotein produced in genetically engineered mammalian cells. 176 Feb 29

A protein profile has been monitored during human immunodeficiency virus (HIV) infection. The investigation concerned 60 patients suffering from acquired immunodeficiency syndrome (AIDS), 24 asymptomatic HIV-antibody seropositive subjects and 22 healthy HIV-antibody seronegative, individuals voluntary blood donors. Data show that retinol-binding protein, thyroxin-binding prealbumin and beta 2-microglobulin are already modified in HIV infection (p less than 0.05) whereas the other protein alteration becomes apparent during AIDS. These studies demonstrate that severe, but progressive malnutrition occurs in patients with AIDS. On the other hand nutritional abnormalities can be shown to have a deleterious effect upon the disease course as revealed by increasing alpha-1-acid glycoprotein and C-reactive protein levels for 60 to 70% of patients.
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PMID:[Inflammatory reaction markers and nutritional markers in HIV infection]. 177 13

Western blot (WB) analysis of various strains of HIV-2 indicated that transmembrane glycoprotein (TMP) of HIV-2 exists as trimers. These trimers have molecular weights and electrophoretic mobilities in the region of the major external glycoprotein, gp120, resulting in WB misidentification during diagnosis. A simple and rapid procedure was developed using trichloroacetic acid (TCA) to efficiently dissociate oligomeric forms of the TMP to monomers prior to the preparation of WB. This procedure permitted the unambiguous identification of antibodies to gp120 and to the TMP. Use of HIV-2 WB strips without any oligomeric forms of the TMP demonstrated (1) that cross reactivity of HIV-1-positive specimens on HIV-2 WB was mainly directed to Gag and Pol proteins, with some reactivity to gp36/gp41 TMP, but none to gp120; (2) that these strips can substantially reduce the number of specimens falsely identified as dually (HIV-1 and HIV-2) reactive; and (3) that HIV-2-positive specimens reacted to viral gp120 in a strain-specific manner, demonstrating high antigenic variation in this glycoprotein. It is recommended that this general procedure of viral protein dissociation be used for HIV-2 WB preparation.
AIDS 1991 Aug
PMID:Oligomeric nature of transmembrane glycoproteins of HIV-2: procedures for their efficient dissociation and preparation of Western blots for diagnosis. 177 59

Altered T cell adherence after human immunodeficiency virus 1 (HIV-1) infection may contribute to viral pathogenesis in the acquired immune deficiency syndrome. To address this hypothesis, we assessed mechanisms of T cell adherence to extracellular matrix proteins in vitro. We found that after HIV-1 infection, both chronically infected H9 CD4+ T cells and acutely infected primary peripheral blood lymphocytes acquired the ability to adhere to the extracellular matrix glycoprotein fibronectin, to a lesser extent to type IV collagen and laminin, but not to type I collagen. H9 cells chronically infected with two of the three HIV-1 strains studied showed approximately a sevenfold increase in attachment to fibronectin, while the same cells infected with the human retrovirus HIV-2 did not. Adhesion was accompanied by changes in morphology, including marked spreading and increased filopodia. These alterations were not blocked by the protein kinase C inhibitor H-7, which did inhibit TPA-induced T cell attachment to fibronectin. Monoclonal antibodies against both the alpha 5 and the beta 1 subunits of the classical fibronectin receptor as well as an Arg-Gly-Asp (RGD) peptide inhibited attachment, whereas anti-alpha 4 monoclonal antibodies and the CS1 peptide did not. Binding to collagen IV was also inhibited by the anti-beta 1 monoclonal antibody, but not the other antibodies. Cells metabolically labeled with [35S]methionine and analyzed by immunoprecipitation with polyclonal anti-beta 1 integrin antibody showed a 2.5-fold increase in integrin synthesis in infected cells compared to uninfected controls. This increase in synthesis was associated with an increase in cell surface expression of both alpha 5 and beta 1 integrins by FACS (registered trademark of Becton Dickinson for a fluorescence-activated cell sorter) analysis. Enhanced expression of integrins such as alpha 5 beta 1 may cause T cell adherence to a variety of tissues, where released viral gene products may induce some of the tissue-specific manifestations of HIV-1 infection.
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PMID:HIV-1 infection of human T lymphocytes results in enhanced alpha 5 beta 1 integrin expression. 183 Dec 4


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