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

Positively charged amino acid substitutions at positions 11 and 25 within the loop of the third variable region (V3) of HIV-1 subtype B envelope have been shown to be associated with the syncytium-inducing (SI) phenotype of the virus. The present study was designed to examine SI and NSI-associated V3 mutations in HIV-1 subtypes other than B. HIV-1 RNA was isolated from 53 virus stocks and 26 homologous plasma samples from 53 recently infected individuals from Brazil, Rwanda, Thailand, and Uganda. The C2-V3 region of the viral envelope was converted to cDNA, amplified, and sequenced. Of 53 primary virus stock samples 49 were biologically phenotyped through measurement of the syncytium-inducing capacity in MT-2 cells (to differentiate between SI and NSI phenotypes). In addition, after passage of primary isolates through PHA stimulated donor PBMC, the replication capacity was determined in U937-2, CEM, MT-2, and Jurkat-tat cell lines (to differentiate rapid/high and slow/low phenotypes). According to the sequence analysis 9 (17.0%) of the viruses belonged to subtype A, 15 (28.3%) to subtype B, 1 (1.9%) to subtype C, 13 (24.5%) to subtype D, and 15 (28.3%) to subtype E. Sequence analysis of virus RNA, obtained from 26 homologous plasma samples, confirmed the homogeneity of sequence populations in plasma compared to primary virus isolates. Of the 49 viruses tested 12 had the SI phenotype, 5 were confirmed to be rapid/high, and 4 appeared to be slow/low pattern 3 replicating. Of 49, 29 had the NSI phenotype, 24 were confirmed to be slow/low pattern 1 or 2, and 3 appeared to be slow/low pattern 3 replicating. Analysis of mutations at V3 loop amino acid positions 11 and 25 revealed that 10/12 (83.3%) of the SI viruses had SI-associated V3 mutations and that 28/29 (96.6%) of the NSI viruses lacked these mutations. V3 loop heterogeneity, length polymorphism, and a high number of positively charged amino acid substitutions were most frequently found among subtype D variants. These results indicate that both the phenotypic distinction between SI and NSI viruses and the association of biological phenotype with V3 mutations is present among HIV-1 subtypes other than B.
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PMID:Syncytium-inducing and non-syncytium-inducing capacity of human immunodeficiency virus type 1 subtypes other than B: phenotypic and genotypic characteristics. WHO Network for HIV Isolation and Characterization. 788 92

HIV-1 isolates were obtained from four countries within the framework of the WHO Network for HIV Isolation and Characterization. The use of standard HIV isolation procedures allowed us to compare the biological properties of 126 HIV-1 isolates spanning five genetic subtypes. In primary isolation cultures, viruses from Uganda and Brazil appeared early and replicated without delay, whereas the replication of Thai viruses was delayed by several weeks. Regardless of genetic subtype or country of origin, blood samples collected more than 2 years after seroconversion yielded virus that replicated efficiently in the primary isolation cultures. None of the isolates obtained from Thailand or Rwanda replicated in cell lines, whereas 5 of the 13 Brazilian isolates and 7 of the 11 Ugandan isolates replicated and induced syncytia in MT-2 cells. As expected for virus isolates obtained early in HIV-1 infection (within 2 years of seroconversion), all viruses from Brazil, Rwanda, and Thailand showed a slow/low replicative pattern. For the Ugandan samples, the time from seroconversion was known precisely for a few of the samples and only in one case was less than 2 years. This may explain why the five viruses that were able to replicate in all cell lines, and thus classified as rapid/high, were of Ugandan origin. Viruses able to induce syncytia in MT-2 cells, also induced syncytia in PBMC. However, 8 slow/low viruses (out of 27) gave discordant results, inducing syncytia in PBMC but not in MT-2 cells. Furthermore, using syncytium induction as a marker, changes in virus populations during early in vitro passage in PBMC could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Standard conditions of virus isolation reveal biological variability of HIV type 1 in different regions of the world. WHO Network for HIV Isolation and Characterization. 788 93

We have reported that amphipathic helical segments in the cytoplasmic domain of the HIV-1 envelope glycoproteins bind to calmodulin (CaM) with high affinity, and inhibit calmodulin-regulated proteins. To investigate the possible role of calmodulin activity in HIV-1 replication, we investigated the anti-HIV activity of various CaM antagonists--trifluoperazine and naphthalenesulfonamide W13 or W7--in HeLa T4 cells, PBMCs, and various T lymphocytic cell lines. The different CaM antagonists were found to inhibit the proliferation of the different cell types to varying extent. Also, the CaM antagonists were found to exert a greater antiproliferative effect on H9/HIV-1IIIB, as compared to uninfected H9 cells, suggesting a deficit of CaM function in HIV-infected cells. The CaM antagonists inhibited virus-induced cell fusion in HeLa T4 cells infected with a recombinant vaccinia virus expressing HIV-1 envelope proteins at threshold concentrations that do not inhibit cell proliferation. The fusion-inhibitory effects of the CaM antagonists were also observed in cocultures of HIV-infected (H9/HIV-1IIIB) and uninfected H9 cells. Under these conditions, the synthesis and surface expression of the viral glycoproteins were not affected, although the kinetics of processing of HIV envelope precursor was delayed. Virus production from both HIV-infected peripheral blood mononuclear cell (PBMC) and MT-2 cell cultures was inhibited by CaM antagonists at concentrations that were inhibitory to cell proliferation. Surprisingly, threshold concentrations of CaM antagonists that do not inhibit cell proliferation were found to enhance virus production from HIV-infected MT-2 cells, but not PBMCs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calmodulin antagonists inhibit human immunodeficiency virus-induced cell fusion but not virus replication. 788 3

Continuing controversy surrounds the cellular effects of the Nef protein of HIV-1, a nonstructural protein expressed by most isolates. Highly purified protein isoforms of MW 27 kDa (Nef 27) and 25 kDa (Nef 25), produced in Escherichia coli by translation from the first and second start codons of HIV-1 nef clone pNL4.3, respectively, were introduced into cells by a sophisticated electroporation technique which uses electric field rather than electric charge to transfer macromolecules across cell membranes. Electroporation of Nef 27 reduced the expression of cell surface CD4 by 30-50%, as measured by flow cytometry, on phytohemagglutinin (PHA)-activated PBMC as well as on a variety of CD4+ T-cell lines (MT-2, CEM, and Jurkat). Reduction in surface CD4 was observed in all cells of the CD4+ T-cell lines but only in the CD4+ cells of the mixed PBMC population. Electroporation of Nef 27 into MT-2 cells and PHA-activated PBMC also reduced the expression of IL-2R to background levels. Other cell surface antigens analyzed such as CD2, CD7, or transferrin receptor (TfR) were not affected by the introduction of HIV-1 Nef 27. In contrast to the effects of Nef 27, electroporation of Nef 25 into cells at equivalent concentrations did not affect the surface expression of CD4 and IL-2R. These data show that the HIV-1 clone pNL4.3 Nef 27 but not the Nef 25 isoform specifically decreases expression of two cell surface receptors important for antigen recognition of MHC class II antigens and for cell proliferation. Production of Nef 27 during HIV-1 infection of cells of the immune system may contribute to immunodeficiency even in the absence of direct viral cytopathic effects.
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PMID:Nef 27, but not the Nef 25 isoform of human immunodeficiency virus-type 1 pNL4.3 down-regulates surface CD4 and IL-2R expression in peripheral blood mononuclear cells and transformed T cells. 790 28

The ability of human immunodeficiency virus type 1 (HIV-1) isolates to replicate in MT-2 cells was investigated as a prognostic marker for disease progression and CD4+ lymphocyte depletion in 53 HIV-1-infected, asymptomatic individuals. MT-2-negative viruses were isolated from 49% of the patients both early and late during the follow-up period; 38% converted from being MT-2 negative to MT-2 positive, while 11% were MT-2 positive throughout the study. One individual showed a fluctuating virus phenotype. The loss of CD4+ lymphocytes was significantly more rapid in MT-2-positive patients. We found a broad spectrum of CD4+ lymphocyte changes in patients whose virus changed its MT-2 tropism. Our data suggest that the changes could be divided into three general patterns. A stable or slowly decreasing CD4+ lymphocyte count changed into a more rapid fall in 44% of the patients, no significant change in rate of decline could be noted in 44% of the patients, while a stable CD4+ lymphocyte level after a change in MT-2 tropism was noted in 12% of the patients. A correlation between MT-2 tropism and clinical symptoms was also noted. Half of the patients with MT-2-negative virus throughout the study were still asymptomatic after a mean follow-up time of 80 months, while only 15% of those who converted remained asymptomatic. All patients with MT-2-positive viruses at the time of inclusion in the study developed HIV-1-related symptoms, and half of them died during the study. The MT-2 status of 16 patients, could be determined at the time of AIDS diagnosis; 50% were Mt-2 positive, while 50% were MT-2 negative. No difference in AIDS-defining diagnoses or CD4+ lymphocyte counts at the time of diagnosis was noted. Knowledge of the HIV-1 phenotype may improve the early recognition of progressive disease.
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PMID:MT-2 cell tropism as prognostic marker for disease progression in human immunodeficiency virus type 1 infection. 785 99

The antiviral effect of the immunomodulating anti-cancer agent, bestatin, was examined in vitro by exposing MT-4 lymphocytes to HIV in the presence of 10-fold dilutions of drug (range 100 micrograms-100 pg/ml). The reduction in infectivity was measured by p24 ELISA and compared to the effect of established anti-HIV drugs-azidothymidine (AZT) and dextran sulfate. The results indicate that low doses of bestatin (1 microgram/ml) can completely inhibit viral infection resulting either from inoculation with free virus or coculture with infected lymphocytes. Unlike AZT or dextran sulfate, bestatin prevents HIV infection without interfering with the rate of cell growth. No appreciable decrease in HIV production was observed when chronically infected virus-producing T cell lines ie, H9, MOLT-4, HPB-ALL, 8E5 and MT-2 were treated with bestatin. Bestatin appears to act in the early stages of viral penetration, possibly through inhibition of lymphocyte-associated aminopeptidases.
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PMID:Inhibitory effect of the oral immune response modifier, bestatin, on cell-mediated and cell-free HIV infection in vitro. 791 6

The syntheses of several alpha-linked thioglycosidic disaccharides are described, including thiokojibiose octaacetate (1), thionigerose (2), and thioisomaltose (3). The title compounds were synthesized by coupling 2,3,4,6-tetra-O-acetyl-1.5-acetyl-1-thio-alpha-D-glucopyranose (4) with either 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethylsulfonyl-beta-D-manno pyr anose (7), 1,2:5,6-di-O-isopropylidene-3-O-trifluoromethylsulfonyl-alpha-D-++ +allofuranose (15), or methyl 2,3,4-tri-O-acetyl-6-deoxy-6-iodo-alpha-D-glucopyranoside (17), respectively. Thiokojibiose octaacetate in turn was converted to 3,4,6-tri-O-acetyl-2-S-(2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl)-2 -thio-alpha-D-glucopyranosyl bromide (9), which was used to obtain several related disaccharides and one trisaccharide. All of the compounds, including thiomaltose and thiotrehalose, which were resynthesized by known methods, were tested for their anti-HIV activity in either CEM or MT-2 cells. Anti-HIV activity was noted only with thiokojibiose octaacetate and its 1-thio analogue (14), which had IC50 values of 51 and 48 micrograms/mL in CEM cells, respectively.
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PMID:Alpha-(1-->2)-, and alpha-(1-->3)-, and alpha-(1-->6)-linked thioglycosidic disaccharides: syntheses and anti-HIV testing of thiokojibiose octaacetate, thionigerose, and thioisomaltose. 798 17

The correlation of the tropism of human immunodeficiency virus type 1 (HIV-1) isolates for MT-2 cells with response to zidovudine and didanosine treatment and with development of drug resistance was studied. Patients with MT-2-negative but not MT-2-positive HIV-1 had a significant increase in CD4+ lymphocyte counts during the first 6 months of treatment. In both groups and for both drugs, the rate of CD4+ lymphocyte decline decreased after the start of treatment. MT-2-positive isolates were more likely than MT-2-negative isolates to show reduced sensitivity to zidovudine and didanosine. Because the differences in zidovudine sensitivity were first evident after 12 months of treatment, drug resistance was probably not the cause of poor response early in zidovudine treatment in patients with MT-2-positive HIV-1. Thus, patients with MT-2-positive virus have limited benefit from treatment with single nucleoside analogues. Knowledge of MT-2 cell tropism may be important in clinical trials and for choosing treatments for patients.
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PMID:MT-2 cell tropism of human immunodeficiency virus type 1 isolates as a marker for response to treatment and development of drug resistance. 799 74

Human immunodeficiency virus type 1 (HIV-1) produces abortive infections of primary cultures of rabbit peripheral blood mononuclear cells (PMBCs). Mitogen activation of rabbit PBMCs or the addition of exogenous cytokines to the cultures does not change the level of release of the early HIV core protein, p24, into the culture medium. The amount of p24 increases steadily and reaches peak levels about 7 days after infection. HIV-1-specific DNA env sequences are also detected in infected PBMCs. However, reverse transcription of RNA of samples from activated infected cultures to cDNA, followed by amplification by the polymerase chain reaction, revealed transcription of gag, but not env, regions, suggesting that HIV-1 infection of rabbit PBMC does not lead to the replication and maturation of complete HIV-1 virions. In addition, neither CPE nor lytic infection was observed in HIV-1-infected rabbit cells and infectivity could not be transferred from rabbit cells infected with HIV for up to 2 weeks to MT-2 or H9 indicator cell lines. In addition, no CPE was seen in long-term cultures of the HTLV-I-transformed rabbit cell line PLT-1441, after inoculation with HIV. It is concluded that primary rabbit PBMCs may be infectable by HIV-1 but are not permissive for production of infectious virus. This conclusion is consistent with the apparent long-term latent infection seen after inoculation of rabbits with HIV-1 or HIV-1-infected cells.
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PMID:Defective infection of rabbit peripheral blood monocyte cultures with human immunodeficiency virus type 1. 801 89

Human immunodeficiency virus type 1 (HIV-1) isolated from patients with acquired immunodeficiency syndrome (AIDS) shows resistance to 3'azido-3'deoxythymidine (AZT) after one or two years of treatment. AZT also has significant toxic side effects, further limiting its use in the therapy of HIV-1-infected individuals. Dehydroepiandrosterone (DHEA) has been shown to have a broad spectrum of biological functions, to be bioavailable orally and to be relatively nontoxic. Epidemiological studies provide evidence that reduced serum levels of DHEA are related to the progression of AIDS in HIV-1 infection. DHEA has also been shown to inhibit HIV-1 replication in vitro and block HIV-1 reactivation from chronically infected cell lines. However, there have been no reports on the ability of DHEA to inhibit the replication of AZT-resistant strains of HIV-1. We investigated whether DHEA treatment could inhibit replication of AZT-resistant strains of HIV-1. Addition of DHEA to MT-2 cell cultures infected with either AZT-sensitive or AZT-resistant isolates of HIV-1 resulted in dose-dependent inhibition of HIV-1-induced cytopathic effect and suppression of HIV-1 replication as measured by accumulation of reverse transcriptase activity. At a concentration as low as 50 microM, DHEA reduced AZT-resistant HIV-1 replication over 50 percent as measured by cytopathic effect and accumulation of reverse transcriptase activity. This study provides evidence that DHEA can inhibit the replication of AZT-resistant as well as wild-type HIV-1. Since the main targets for DHEA are metabolic and cellular signaling pathways leading to HIV-1 replication-activation, DHEA should be effective against multidrug-resistant strains of HIV-1. Combined with recently discovered immunoregulatory properties, the finding that DHEA is able to inhibit replication of both wild-type and AZT-resistant HIV-1 suggests that in vivo DHEA may have a much broader spectrum of action than originally anticipated.
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PMID:Inhibition of 3'azido-3'deoxythymidine-resistant HIV-1 infection by dehydroepiandrosterone in vitro. 802 87


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