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

A region of homology has been found between the envelope (env) protein of the acquired immunodeficiency syndrome (AIDS) virus and a portion of interleukin 2 (IL-2) that purportedly binds to the IL-2 receptor. This homology, between two proteins associated with opposing biological functions, suggests possible mechanisms for the immunosuppressive activity of the AIDS virus. Two mechanisms are proposed in which the AIDS virus env protein interferes with IL-2 activity either directly or indirectly. A region of similarity to the purported IL-2 receptor binding site on IL-2 and AIDS virus env is present in the env proteins of other retroviruses associated with immunosuppression. A synthetic peptide vaccine for AIDS is suggested based on the IL-2 receptor binding sequence in AIDS virus env.
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PMID:Sequence homology between acquired immunodeficiency syndrome virus envelope protein and interleukin 2. 302 69

The first experimental immunization of humans against the AIDS retrovirus, HIV-1, was started in a series of HIV seronegative, healthy volunteers in November 1986. For the primary vaccination recombinant vaccinia virus (V25) expressing the complete gp160 env protein of the HTLV-IIIB strain of HIV-1 was introduced by scarification. This elicited a weak primary response which we subsequently attempted to enhance by additional immunizations (boosting), using four different immunization protocols. We report here that intravenous injection of paraformaldehyde-fixed autologous cells infected in vitro with V25 (individual D.Z.) gave the best results. This individual received second and third boosts of intramuscular gp160 derived from an HTLV-IIIB clone using the hybrid vaccinia virus/bacteriophage T7 expression system. An anamnestic humoral and cellular immune reaction was achieved for over one year after the original vaccination, with high levels of antibodies to the viral envelope, and neutralizing antibodies against divergent HIV-1 strains such as HTLV-IIIB and HTLV-IIIRF (also called HTLV-III HAT) after the first boost. In addition, group-specific cell-mediated immunity and cell-mediated cytotoxicity against infected T4 cells were obtained after the primary vaccine and enhanced by the boosts. Finally, skin tests showed both immediate and delayed hypersensitivity to gp160 in vivo. Although this protocol is not practical for a large scale vaccine trial, our results show for the first time that an immune state against HIV can be obtained in man.
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PMID:A group specific anamnestic immune reaction against HIV-1 induced by a candidate vaccine against AIDS. 316 62

The 1st experimental immunization of humans against the AIDS retrovirus HIV-1 was begun in November 1986 among a group of HIV-seronegative healthy volunteers. A priming, involving a vaccine virus recombinant (V25) expressing Gp 160 env determinants of HTLV-III B at the surface of the infected cells was utilized. This priming, which induced a weak immune reaction, was performed on HIV-seronegative French and Zairian individuals living in Kinshasa, Zaire. These results prompted a boost to the primary immune response. 4 different protocols were used: the slow drip intravenous infusion with paraformaldehyde-fixed autologous cells infected with V25; repeated scarification with V25 for the 2nd protocol; scarifications with fragments of Gp 120 env protein; and intramuscular injections of purified autologous cell membrane infected with V25. The results of the immune reaction obtained after these boosts indicated the following: The last 3 protocols showed a cell- mediated immunity (CMI) that did not significantly enhance in comparison with CMI obtained after V25 priming alone. Moreover, the sera showed low and variable neutralizing antibody titers 1-4 months after boosting. By contrast, boosting with V25 infected fixed cells (D.Z.) provided strong humoral and cellular group specific anamnestic immune responses. Indeed, high levels of antibodies to viral envelope and neutralizing antibodies against divergent HIV-1 strains were observed. Group- specific CMI and cell mediated cytotoxicity were enhanced by boosts. Skin tests showed high mediated and delayed hypersensitivity to Gp 160 in vivo. For the 1st time, these results show that an immune state against HIV can be obtained in a man. (author's modified)
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PMID:[Immunization against the human immunodeficiency virus in Zaire]. 322 92

There is increasing evidence for the link between members of the human T-lymphotropic virus family and clinically important disease. We used indirect membrane immunofluorescence (IMI) to screen patient and control sera for antibodies to human T-cell leukemia virus (HTLV) specific cell membrane antigens (HTLV-MA) of HTLV-I and HTLV-III. Representative sera were screened for antibodies to specific HTLV-encoded proteins using radioimmunoprecipitation (RIP) with SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Essentially all Japanese patients with adult T-cell leukemia/lymphoma (ATLL) from Miyazaki, Japan had detectable antibodies to HTLV-I-MA, further supporting the evidence for the probable etiologic relationship of HTLV-I and ATLL. While 16% of the healthy adults from this endemic region had antibodies to HTLV-I-MA, such antibodies were also found in 42% of the adults hospitalized in Miyazaki with severe infections diseases. Other studies have demonstrated HTLV-I antibodies in 12% of asymptomatic hemophiliacs examined from various U.S. cities. We have previously shown that HTLV-I status positive antibody in hemophiliacs is accompanied by a decrease in the number of T helper cells. Patients seropositive for antibodies to HTLV-I-MA regularly demonstrated antibodies to the env gene encoded gp61 proteins, while lower but significant proportions had antibodies to the gag and lor gene proteins. These and other observations suggest that infection with at least some strains of HTLV-I may be associated with mild or transient immunosuppression, in the absence of leukemia. Analysis by RIP indicated that gp61 and gp45, both encoded by the env gene of HTLV-I, are the most immunogenic proteins of the virus. The gp61 HTLV-I is highly crossreactive with gp67, the major env protein of HTLV-II. Patients with acquired immune deficiency syndrome (AIDS) were also examined for antibodies to HTLV-I-MA and antibodies to the gag, env, and lor gene proteins by RIP. Antibodies were detected in 38-75% of the patients, the higher percentage reflecting the presence of at least one positive sample in those individuals where more than three serial serum samples were tested. Numerous control groups were essentially seronegative for antibodies to HTLV-I proteins. When AIDS patient sera were examined for antibodies to HTLV-III, 95-100% were seropositive. Such antibodies were also found in the majority of asymptomatic Boston-areas hemophiliacs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:HTLV and immunosuppression. 610 Jun 49

The pathology in central nervous system (CNS) AIDS suggests that direct infection with HIV-1 is not required for changes in glia and neurons. Induction of a variety of pathological responses in vitro in rodent brain cultures also suggests that CD4 is not the receptor for HIV-1 in the brain, given that human and rodent CD4 are not homologous. This implies that the epitopes on HIV-1 which bind glia and activate them are novel, non-CD4-binding domains. We have therefore mapped the envelope (env) regions required for production in rat glial cultures of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) which we hypothesize are important in CNS AIDS. Serially truncated deletion mutants from the gp120/gp41 carboxy terminus representing folded, glycosylated recombinant env proteins were expressed in HeLa cells via a vaccinia virus vector. These proteins, linear gp120/gp41 peptides, as well as polyclonal and monoclonal antibodies reactive to defined regions of gp120/gp41 were used to map the epitopes involved in production of IL-1 and TNF alpha. Compared to HeLa cell and wild-type vaccinia virus controls, the vaccinia recombinant env protein gp160 containing cleaved gp120 and gp41 induced both IL-1 and TNF alpha. If gp160 was not cleaved into gp120 and gp41, IL-1 but not TNF alpha induction was reduced. Peak production of TNF alpha by gp120/gp41 was at 4 h while IL-1 production was still significantly elevated at 44 h at the highest concentrations of env protein. Using the truncation deletions, the V3 loop of gp120 appeared to be critical for IL-1. Glycosylation and folding of V3 is probably important in IL-1 induction since a V3 peptide was not as active. While removal of glycosylated, folded V4 and C4 regions had no effect on IL-1, linear peptides in the region from the V4 loop to the C4 domain were strong inducers of IL-1. Non-glycosylated, linear V4 loop peptide induced more IL-1 than the V4 in protein generated in HeLa cells, suggesting that glycosylation and/or conformational structures sequester V4 inducer epitopes. Using the truncation deletions, the carboxy terminus region (V4-C5) of gp120 as well as gp41 were shown to be critical for TNF alpha production. Peptides representing linear epitopes in the V3 loop, C5 domain of gp120, and the ectodomain of gp41 were all strong inducers of TNF alpha; a protein representing almost the entire gp41 was the strongest inducer of TNF alpha.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The mapping of HIV-1 gp160 epitopes required for interleukin-1 and tumor necrosis factor alpha production in glial cells. 770 35

Although both HIV-1 subtypes B and E have been identified from infected individuals in Thailand, subtype E is the main form of HIV currently circulating in the country. Full-length gp160 sequences were obtained from 2 early seroconverters from northern Thailand in a study to learn more about the HIV-1 sequences currently being transmitted among recently infected individuals. Subject A01021 was a female prostitute who tested negative for antibodies to HIV-1 in April 1993, then positive in July 1993. Subject E11429 was a male military conscript who tested negative for antibodies to HIV-1 in May 1993, then positive in November 1993. Uncultured peripheral blood mononuclear cells (PBMCs) were collected from these two individuals in January 1994 and about 2500-bp segments containing the full-length gp160 gene were amplified by nested polymerase chain reaction (PCR) using the Expand high-fidelity PCR system. The nucleotide sequences of full-length gp120 from the subjects were subtype E based upon phylogenetic analysis. The gp120 sequences from the 2 seroconverters appeared more diverse than previously published subtype E HIV-1 sequences from Thailand. Overall, however, the subtype E HIV-1 gp120 sequences from Thailand were less diversified compared to the subtype E HIV-1 isolated from people with AIDS in the Central African Republic. Most of the observed amino acid variations were limited to the 5 variable regions in gp120. Therefore, vaccine strategies which elicit immune responses to the conserved regions of HIV-1 env protein will have a greater possibility of success.
AIDS Res Hum Retroviruses 1997 Nov 01
PMID:Diversity of full-length subtype E HIV type 1 env sequences in early seroconvertors from northern Thailand. 935 64

Intracellular expression of genes that inhibit key steps in the human immunodeficiency virus (HIV-1) replicative cycle could offer an alternative therapy for AIDS treatment. One of these approaches involves the inhibition of env protein maturation through the expression of CD4 molecules with added exogenous sequences that promote their retention in the endoplasmic reticulum (ER). We have tested this strategy using a CD4 chimera (CD4epsilon10) containing an ER retention sequence derived from the TCR CD3-epsilon chain. Transfection of CD4epsilon10 in the human T cell line Jurkat made it resistant to infection with two different HIV-1 isolates, which was evaluated by measuring p24 antigen production, induction of apoptosis, and syncytia formation. Furthermore, polymerase chain reaction (PCR) analysis of genomic DNA showed no traces of the proviral HIV-1 genome in CD4epsilon10-transfected cells, suggesting it was not maintained latently in these cells. To facilitate the delivery of the CD4epsilon10 chimera to primary cells from AIDS patients, a Moloney-based retroviral vector was constructed that expresses CD4epsilon10 under the transcriptional control of the HIV-1 long terminal repeat (LTR) promoter. Transduction of the MT-2 human T cell line with this vector rendered it resistant to infection with HIV-1 by a process that involved the inhibition of gp160 proteolytic processing. Finally, transduction of the CD4epsilon10 chimera into T lymphoblasts derived from asymptomatic HIV-infected individuals demonstrated a protective effect, resulting in both an increased cellular proliferation rate and an increased percentage of CD4+ cells. These results suggest that it is feasible to use retroviral transduction of CD4epsilon10 as a gene therapy approach for AIDS treatment.
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PMID:Retroviral vector-mediated expression in primary human T cells of an endoplasmic reticulum-retained CD4 chimera inhibits human immunodeficiency virus type-1 replication. 965 Jun 19

With the aim to determine if immunization with two different live recombinant viral vectors could lead to an enhancement of the cellular immune response to HIV-1 antigens, we have characterized the CD8+ T cell response elicited against the V3 loop epitope from HIV-1 env protein in Balb/c mice immunized with either: a recombinant influenza virus (Flu-Env) expressing the V3 loop epitope from HIV-1 strain IIIB, a vaccinia virus recombinant (VV-Env) expressing the complete HIV-1-IIIB env protein, or a combination of both. The CD8+ T cell response, measured by the ELISPOT assay, in animals primed with Flu-Env and boosted with VV-Env was 5 to 6 times higher than in animals inoculated with either Flu-Env or VV-Env alone. Similar results were obtained with recombinant viruses expressing the V3 loop epitope or the complete env protein, respectively, from the MN strain of HIV-1. Our results indicate that the use of two different live vectors for priming and boosting has a synergistic effect on the immune response against HIV-1, and could represent a novel vaccination strategy against AIDS.
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PMID:Enhanced CD8+ T cell response to HIV-1 env by combined immunization with influenza and vaccinia virus recombinants. 1006 95

The physiopathology of HIV-1 dementia remains largely hypothetical. Although several sets of evidence point towards an indirect multicellular inflammatory pathway, gp120, one of the HIV-1 env products, was shown to be very cytotoxic for neurons in vitro. To explore a direct pathway in the physiopathology of dementia in AIDS, we developed transgenic mouse models carrying the HIV-1 env proteins gp 120 and gp 41 (gp 160) under the control of the human light neurofilament and murine heavy neurofilament promoters. To date, this is the first mouse model in which the HIV-1 env protein can be detected in neurons by immunohistochemistry. The expression is found in several brainstem and spinal cord gray structures and in the cerebellum in one of the mouse lines bearing the NFHgp160 transgene. The morphological findings at 3 months are subtle and are dominated by a watery, dendritic degeneration and a reactive gliosis. At 12 months, the evidence of neuronal degeneration and loss is present along with various degenerative phenomena involving synapses, dendrites and axons, including axonal swellings. Cytoskeletal abnormalities were found by immunohistochemistry. Chronic inflammation was also observed in the leptomeninges of the spinal cord and brainstem and in the cerebellar white matter. These models thus offer an exciting sequence of morphological findings initiated by the neuronal expression of the HIV-1 env proteins and offer a different tool to explore the neuronal dysfunction in AIDS.
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PMID:Neuropathology of NFHgp160 transgenic mice expressing HIV-1 env protein in neurons. 1139 34

HIV-1 viral proteins, particularly the env protein, are homologous to 22 AIDS autoantigens, suggesting their creation by antiviral antibodies subsequently targeting human homologues. They include antibodies to T-cell receptors, CD4 and CD95, complement components, IgG, TNF and other immune-related proteins. Autoantibodies may compromise the immune system via knockdown of these key proteins, and autoimmune attack on the immune system itself, as supported by immune activation in early stages of infection and during the transition to AIDS. Over 500 human proteins contain pentapeptides or longer consensi, identical to viral peptides. Such homology explains the extensive viral/human interactome, likely related to the ability of viral homologues to compete with human counterparts as binding partners. Pathway analysis of these homologous proteins revealed their involvement in immune-related networks (e.g. natural killer cell toxicity/toll, T-cell/B-cell receptor signalling/antigen processing) and viral and bacterial entry and defence pathways (phagosome/lysosome pathways, DNA sensing/NOD/RIG-1 pathways) relevant to AIDS pathogenesis. At its inception, AIDS may have an autoimmune component selectively targeting the immune system. Immunosuppressive therapy or antibody removal, which has already achieved some success, might be therapeutically beneficial, particularly if targeted at removal of the culpable antibodies, via affinity dialysis.
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PMID:Extensive viral mimicry of 22 AIDS-related autoantigens by HIV-1 proteins and pathway analysis of 561 viral/human homologues suggest an initial treatable autoimmune component of AIDS. 2207 29

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