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

Seven diverse primary isolates of human immunodeficiency virus type 1 (HIV-1) were examined and found to be refractory to neutralization by antisera to recombinant gp120 (rgp120) protein from HIV-1 MN. This stands in marked contrast to the sensitivity exhibited by certain laboratory-adapted viruses. To understand the difference between primary and laboratory-adapted viruses, we adapted the primary virus ACH 168.10 to growth in the FDA/H9 cell line. ACH 168.10 was chosen because the V3 region of gp120 closely matches that of MN. After 4 weeks, infection became evident. The virus (168A) replicated in FDA/H9 cells with extensive cytopathic effect but was unchanged in sensitivity to antibody-mediated neutralization. Thus, growth in cell lines is not sufficient to render primary virus sensitive to neutralization. The 168A virus was, however, partially sensitive to CD4 immunoadhesin (CD4-Ig). Adaptation was continued to produce a persistently infected FDA/H9 culture that displayed minimal cytopathic effect. The virus (168C) was now sensitive to neutralization by MN rgp120 vaccine sera and by MN-specific monoclonal antibodies and showed increased sensitivity to HIVIG and CD4-Ig. 168C encoded three amino acid changes in gp120, including one within the V3 loop (I-166-->R, I-282-->N, G-318-->R). MN-specific monoclonal antibodies bound equally to the surface of cells infected with either neutralization-resistant or -sensitive virus. The coincidence of changes in neutralization sensitivity with changes in cell tropism and cytopathic effect suggests a common underlying mechanism(s) acting through the whole of the envelope protein complex.
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PMID:Adaptation to persistent growth in the H9 cell line renders a primary isolate of human immunodeficiency virus type 1 sensitive to neutralization by vaccine sera. 798 34

Apoptosis is an important regulatory process during normal development and maturation. We find that the proliferation-arresting and differentiation-inducing compound sodium n-butyrate (NaB) triggers a marked host chromatin degradation. This apoptotic process is independent of, but commensurate with, a rapid increase in viral mRNA synthesis and subsequent release of HIV-1 virus in transformed human cell lines harboring tat- (HLM1) or tat+ (U1, ACH-2) dormant HIV-1 proviruses. This compound stimulates a reversible accumulation of the characteristic viral mRNAs at a much faster rate than two other DNA degradation inducers such as tumor necrosis factor-alpha and phorbol 12-myristate 13-acetate. The transcriptional activator butyrate analogue, alpha-amino-n-butyrate, failed to cause similar phenotypic changes. These results suggest that common regulatory signals may be involved in activation of apoptosis genes and latent provirus by NaB.
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PMID:Induction of developmentally programmed cell death and activation of HIV by sodium butyrate. 800 66

In this study, we have examined whether the Tat antagonist can inhibit human immunodeficiency virus type 1 (HIV-1) replication in the presence of cofactors that can activate transcription of HIV-1 provirus by an NF-kappa B-mediated mechanism, such as tumor necrosis factor-alpha (TNF-alpha) or herpes simplex virus type 1 (HSV-1) infection. As a prototype, we have chosen a low-molecular-weight Tat inhibitor, Ro5-3335, and analyzed its effect on HIV-1 replication in the presence of TNF-alpha and HSV-1 infection in acutely infected peripheral blood lymphocytes (PBLs) and T cells. Ro5-3335 inhibited HIV-1 replication both in CEM-174 cells and in PBLs, but the magnitude of the inhibition was inversely related to viral inoculum and the inhibition was only temporary; viral replication resumed at later times postinfection in spite of the continuous presence of the drug. In contrast, Ro5-3335 suppressed TNF-alpha-induced activation of HIV-1 replication in chronically infected T cells and monocytes that both expressed only low levels of HIV-1 constitutively, while its effect in high-expressing OM-10.1 cells was negligible in the presence of TNF-alpha. The inhibition of HIV-1 replication by Ro5-3335 was specific for the Tat-mediated effect and this drug was not able to inhibit the TNF-alpha-induced expression of the tat-defective HIV-1 provirus. In contrast to TNF-alpha, HSV-1-stimulated HIV-1 expression in the ACH-2 cells was effectively inhibited in the presence of Ro5-3335. These results demonstrate that Tat plays an essential role in HSV-1-mediated activation of HIV-1 provirus, while the TNF-alpha complementation of Tat shows cell-type specificity. These observations suggest that inhibition of the Tat function alone may not be sufficient for an effective anti-HIV-1 inhibition.
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PMID:Differential effect of tumor necrosis factor-alpha and herpes simplex virus type 1 on the Tat-targeted inhibition of human immunodeficiency virus type 1 replication. 803 Feb 18

In vivo infection of human T cell lymphocytes by HIV-1 is mediated by the specific binding of the HIV-1 envelope glycoprotein gp120 to the T cell CD4 receptor. One of the post-infection events observed in vivo is the progressive loss of CD4+ T cells. One possible mechanism is the production of infected T cells which are lacking in surface expression of the CD4 receptor protein. We have analysed this possibility utilizing the two HIV-1 chronically-infected CD4- cell lines, 8E5 and ACH-2, both of which are derived from a CD4+ parental strain (A3.01) after HIV-1 infection. In each cell (8E5 and ACH-2) the loss of CD4 surface expression was found to occur by different mechanisms. In ACH-2 cells, neither CD4 protein nor the 3 kb CD4 RNA transcript could be detected. However, treatment of ACH-2 cells with cycloheximide elicited production of the 3 kb transcript suggesting the possibility for a repressor protein(s) to act at the level of transcription and/or stability of the 3 kb mRNA. In contrast, in 8E5 cells the level of the 3 kb CD4 RNA was comparable with that found in the CD4+ A3.01 parental strain. Analysis of the 8E5 strain revealed the presence of a CD4- gp160 bimolecular protein complex sequestered internally in the rough endoplasmic reticulum (RER). Finally, the protein tyrosine kinase p56lck, normally associated with the cellular membrane, appeared to be linked to the RER and bound to the CD4- gp160 proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transcriptional and post-transcriptional mechanisms are involved in the absence of CD4 surface expression in two HIV-1 chronically infected T cell lines. 810 73

An in vitro model of placental infection by human immunodeficiency virus type 1 (HIV-1) was established using human choriocarcinoma-derived trophoblast lines exposed to free HIV-1 or HIV-1-infected lymphocytic and monocytic cells. Virus infectivity was evaluated by measuring both the levels of p24 HIV-1 antigen and reverse transcriptase activity either from indicator MT-4 lymphocytes after co-cultivation with infected trophoblasts or directly from trophoblast cultures. None of the tested trophoblast lines were permissive, in a detectable manner, to infection by cell-free virus. Furthermore, there were no signs of infection when trophoblasts were exposed to HIV-1-carrying ACH-2 and U1 cells with impaired adhesion capacity. However, the exposure to MOLT-4/IIIB lymphocytes or U937/YH5 monocytes that adhere to substrate cells resulted invariably in productive infection. The ultrastructure of the trophoblasts suggests endocytosis of HIV-1. It appears that the infection of the host cell results from the escape of virions from degradation in lysosomes. Alternatively, HIV-1 may enter by budding directly from the lymphocyte surface into the cytoplasm of trophoblasts. These results confirm previous studies and suggest that CD4-negative placental trophoblasts--the only foetal cells in direct contact with maternal blood--can be susceptible to HIV-1 infection.
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PMID:Human immunodeficiency virus type 1 infection of choriocarcinoma-derived trophoblasts. 810 49

Human immunodeficiency virus type 1 (HIV-1) can infect various cell lines in culture and be maintained in a chronic state of restricted replication. These states of proviral latency are characterized by a predominance of spliced compared to unspliced viral RNA species. The proximate molecular mechanisms leading to restricted HIV-1 replication may differ in various cell lines. Importantly, recent studies have demonstrated that the site of integration is the critical parameter leading to proviral latency in ACH-2 cells. Utilizing murine retroviral shuttle vectors, the HIV-1 Tat protein was demonstrated to dramatically increase HIV-1 expression in the restrictively infected U1 monocytic cell line but not in the ACH-2 T-lymphocytic line. The HIV-1 Rev protein only modestly increased viral expression in both of these cell types. Thus, these data support the hypothesis that the mechanisms which initiate and/or maintain restricted HIV-1 expression may differ in various cell types in cell culture, and possibly in vivo.
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PMID:Tat and rev differentially affect restricted replication of human immunodeficiency virus type 1 in various cells. 812 76

An important aspect of infection by the human immunodeficiency virus (HIV-1) type 1 is its long clinical latency period, suggesting that the provirus may remain latent for extended periods of time after primary infection. Numerous factors such as cytokines, tumor promoters, co-infection by several viruses and physical agents are able to reactivate latent virus. Since a common denominator, shared by several of these agents, is their ability to cause stress conditions, we have examined the effects of an oxidative stress mediated by reactive oxygen species on HIV-1 latently infected monocytes (U1) or lymphocytes (ACH-2). Exposure of these two cell lines to hydrogen peroxide causes a decrease of cell viability but among the cells surviving the treatment, a HIV-1 reactivation can be observed as measured by increased RT activities depicted in cell supernatants or by the appearance of HIV-1 antigens inside cells. Singlet oxygen (1O2) when generated either in the cytoplasm or in the cell nucleus can also promote an important HIV-1 reactivation from treated cells. However, extracellular generation of 1O2 cannot trigger the HIV-1 reactivation although this kind of treatment is highly cytotoxic. These experiments demonstrate that different reactive oxygen species are able to lead to an intracellular pro-oxidant state initiating one or several signalling pathways which lead in fine to the HIV-1 LTR transactivation by regulatory proteins.
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PMID:HIV-1 reactivation after an oxidative stress mediated by different reactive oxygen species. 819 37

The oral anticoagulant warfarin (4-hydroxy-3-(3-oxo-1-phenylbutyl)- benzopyran-2-one) is a structurally novel low micromolar competitive inhibitor of HIV-1 protease in vitro. It was recently reported that warfarin inhibits HIV-1 infection in U-1 monocytes and viral production in ACH-2 lymphocytes (Bourinbaiar, A.S. et al., (1993) AIDS 7, 129-130). Our results demonstrate that warfarin and a series of structurally related analogs inhibit the viral protease, the most potent analog having an IC50 = 1.9 microM. Kinetic analysis reveals inhibition by warfarin occurs in a competitive manner, with Ki = 3.3 microM. While it is unclear whether the cellular inhibition previously reported is due to inhibition of HIV-1 protease, the warfarin analogs are a novel class of nonpeptide HIV-1 protease inhibitors.
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PMID:Competitive inhibition of HIV-1 protease by warfarin derivatives. 819 86

The p53 tumor suppressor gene product, a sequence-specific DNA-binding protein, has been shown to act as a transcriptional activator and repressor both in vitro and in vivo. Consistent with its role in regulating transcription are recent observations that the N-terminal acidic domain of p53 binds directly to the TATA box-binding protein subunit of the general transcription factor, TF IID. It is now demonstrated that wild-type p53 (wt-p53) inhibits human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-directed chloramphenicol acetyltransferase activity in a cotransfection assay system. Importantly, this effect of wt-p53 on the HIV-1 LTR was also demonstrated by in vitro transcription assays. In addition, the Sp1 sites and the TATA box of the HIV-1 LTR are demonstrated to be the primary sites involved with p53-induced effects on this viral promoter. The upstream elements of the HIV-1 LTR, including the nuclear factor kappa B (NF-kappa B) binding sites, decrease the p53-induced inhibitory effects on viral transcription. In the presence of the HIV-1 TAR sequence and Tat protein, the HIV-1 LTR also becomes less sensitive to wt-p53-induced inhibition. By using a retroviral vector delivery system, mutant forms of p53 genes were expressed in two HIV-1 latently infected cell lines, ACH-2 and U1. In the ACH-2 cell line, which is now demonstrated to contain an endogenous mutant form of p53 (amino acid 248, Arg to Gln), additional mutant p53 proteins did not alter HIV-1 replication. In U1 cells, which completely lack endogenous p53, overexpression of mutant p53 led to an increase in HIV-1 replication. Thus, these data indicate a possible functional role for wt-p53 and mutant p53 proteins in the control of HIV-1 replication patterns and proviral latency.
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PMID:The tumor suppressor protein p53 strongly alters human immunodeficiency virus type 1 replication. 820 5

CD8-positive cytotoxic T cells (CTLs) are activated by recognition of peptide bound to MHC class I molecules on target cells. This human leukocyte antigen-restricted process induces not only lysis of target cells but also secretion of lymphokines by the CTLs, including TNF-alpha, TNF-beta, and IFN-gamma. In this study we show that activation of HIV-1-specific CTL clones by their cognate peptide epitopes induces HIV-1 replication in the chronically HIV-1-infected T-cell line ACH-2. The HIV-1-inducing activity correlates with increased levels of TNF-alpha produced by these CTLs, and can be inhibited by anti-TNF-alpha antibodies, indicating that the effect is mediated by this cytokine. These studies suggest that activation of CTL in vivo could lead to enhanced viral replication. Although HIV-1-specific CTLs may serve as a host defense to inhibit virus replication, the induction of TNF-alpha production by these cells may facilitate viral replication in infected bystander cells, contributing to viral persistence and disease pathogenesis.
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PMID:Induction of HIV-1 replication in a chronically infected T-cell line by cytotoxic T lymphocytes. 831 73


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