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

Human immunodeficiency virus (HIV types 1 and 2) replication is controlled by the interaction of viral-encoded regulatory proteins and host cellular proteins with the viral long terminal repeat (LTR). The presence of HIV-1 and HIV-2 trans-activator proteins, tat1 and tat2, respectively, greatly increases viral gene expression from their homologous LTRs. It is unclear if the cellular factors that support tat1-directed trans-activation of the HIV-1 LTR are the same for tat2 trans-activation of the HIV-2 LTR. Human-Chinese hamster ovary hybrid cell clones were used to probe for human chromosomes involved in regulating HIV-1 and HIV-2 tat-directed transactivation. DNA transfection experiments showed that the presence of human chromosome 12 in human-hamster hybrid clones was necessary for high-level tat-directed trans-activation of the HIV-1 and -2 LTR. Cross-trans-activation of the HIV-2 LTR by tat1 was found to be chromosome 12 independent. In addition, chromosome 12 did not support trans-activation of another human retrovirus (human T-cell leukemia virus type I). Our results suggest that HIV-1 and -2 have evolved to employ a cellular pathway(s) encoded on human chromosome 12 for supporting homologous tat-directed trans-activation. Trans-activation of the HIV-2 LTR by tat1 in chromosome 12-minus cells suggests that multiple cellular pathways can be recruited to trans-activate the HIV-2 LTR and that these pathways may have been important in an HIV-like progenitor virus.
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PMID:Human chromosome-dependent and -independent pathways for HIV-2 trans-activation. 176 Feb 28

Kaposi's Sarcoma (KS) is a tumor of mesenchymal origin of unclear etiology and pathogenesis. The epidemic form of KS (AIDS-associated) occurs in up to 30% of HIV-1 infected individuals with lesions characterized by mixed cellularity, spindle cells proliferation and neoangiogenesis. The establishment of in vitro and in vivo model systems (AIDS-KS cell cultures and nude mouse) have allowed studies toward the understanding of the pathogenesis of KS. The data presented here support the hypothesis that KS is a cytokine mediated disease and that interactions between mesenchymal cell types and HIV-1 gene products might lead to a composite lesion such as KS. In fact, in vitro and in vivo studies indicate that the HIV-1 Tat protein acts as a growth factor for cells derived from AIDS-KS lesions, thus establishing an experimental link between HIV-1 infection and the development of KS in humans. Human immunodeficiency virus (HIV-1) is implicated in various clinical manifestations associated with AIDS, including KS. KS represents the most frequent tumor arising in infected individuals, particularly homosexual and bisexual men. This form of KS (epidemic or AIDS-KS) is aggressive and often results in dissemination and invasion of lymph nodes and viscera. Histologically, KS is characterized by the proliferation of spindle-shaped cells ("KS cells"), considered to be the tumor element of the lesions, associated with endothelial cells, fibroblasts, inflammatory cells and new blood vessel formation (early stage lesions). In a later stage, the spindle cells tend to coalesce in larger tumor masses, although the slit-like spaces, which are characteristic of the lesion, usually remain evident. The histogenesis of the KS spindle cells, however, is still controversial and both types of mesenchymal cells, endothelial and smooth muscle cells, have been proposed as potential cell progenitors. Although KS is clearly associated with HIV-1 infection, little is known about the molecular events underlying its pathogenesis. Recently, however, two experimental advances (the establishment of long-term cell cultures derived from KS lesions of AIDS patients and the development of animal models) have made the study of the pathogenesis of AIDS-KS possible. Here we discuss results obtained from these new systems suggesting that the induction of the AIDS-KS lesions involves a pathway of events mediated by specific cytokines and that the HIV-1 tat gene product may play a crucial role in the development and/or progression of KS in HIV-1 infected individuals.
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PMID:Molecular mechanisms in the pathogenesis of AIDS-associated Kaposi's sarcoma. 180 71

A eukaryotic vector-host cell system is described where the additive transactivating effects of HIV-1 tat and adenovirus E1A on HIV-1 long terminal repeat (LTR) are exploited to increase expression of exogenous cDNAs. Human 143B and 293 cells, the latter constitutively producing E1A, were used as host cell lines. The bacterial gene chloramphenicol acetyltransferase (CAT) and the hepatitis B surface antigen (HBs-Ag) gene were employed as reporter genes inserted in pRPneoU3R, an episomal vector containing BK virus replication origin and early region, where cDNAs are expressed under control of HIV-1 LTR. The 293 cells were transformed by tat expression vectors to constitutively express tat. Stable cell clones of 293tat cells, constitutively expressing CAT after transformation with pRPneoU3R-CAT, show a CAT activity 600-fold higher than normal 293 transformed cells. CAT expression obtained in normal 293 cells can be transiently increased 10-fold by transfection by vectors expressing tat. The 293tat cells transformed by pRPneoU3R-HBs, an episomal vector expressing HBs-Ag from HIV LTR, yielded stable cell clones secreting HBs-Ag in the culture medium at a concentration up to 744 ng/ml or 44 ng/10(6) cells/24 h, 48-fold more than normal 293 cells. The use of this system for constitutive or inducible expression of sequences under control of HIV-1 LTR is discussed in view of possible applications for diagnostic, vaccinal and therapeutic purposes.
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PMID:High expression of exogenous cDNAs directed by HIV-1 long terminal repeat in human cells constitutively producing HIV-1 tat and adenovirus E1A/E1B. 182 15

The immunodeficiency virus type 1 is a complex retrovirus. In addition to genes that specify the proteins of the virus particle and the replicative enzymes common to all retroviruses, HIV-1 specifies at least six additional proteins that regulate the virus life cycle. Two of these regulatory genes, tat and rev, specify proteins essential for replication. These proteins bind to specific sequences of newly synthesized virus RNA and profoundly affect virus protein expression. Tat and rev appear to be prototypes of novel eukaryotic regulatory proteins. These two genes may play a central role in regulating the rate of virus replication. Three other viral genes, vif, vpu, and vpr, affect the assembly and replication capacity of newly made virus particles. These genes may play a critical role in spread of the virus from tissue to tissue and from person to person. Our understanding of the contribution of each of the virus structural proteins and regulatory genes to the complex life cycle of the virus in natural infections is incomplete. However, enough insight has been gained into the structure and function of each of these components to provide a firm basis for rational antiviral drug development.
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PMID:Molecular biology of the human immunodeficiency virus type 1. 182 94

Synthetic oligoribonucleotides having single uracil residues replaced by dU, dT, 2'-O-methylU or 5-bromodU have been prepared and used in the study of the interaction of HIV-1 tat protein with an RNA stem-loop. The preparation of phosphoramidites of 5-bromouridine and purine riboside suitable for use in solid-phase oligoribonucleotide synthesis is also described. The effect of adenine replacement by purine in a hammerhead ribozyme has also been determined.
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PMID:Synthesis of site-specifically modified oligoribonucleotides for studies of the recognition of TAR RNA by HIV-1 tat protein and studies of hammerhead ribozymes. 184 80

The adeno-associated virus (AAV) rep gene encodes four proteins (Rep78, Rep68, Rep52, and Rep40) required for AAV DNA replication and AAV gene regulation. In addition, the Rep proteins may have pleiotropic regulatory effects in heterologous systems, and in particular Rep78 may mediate a negative regulatory effect. We analyzed the effects of the AAV rep gene on human immunodeficiency virus type 1 (HIV-1) gene expression. The rep gene proteins of AAV type 2 (AAV2) inhibited the trans-activating ability of HIV-1. Constructs containing the AAV2 rep gene (pHIVrep) or a CAT gene (pBennCAT) expressed from the 5' HIV-1 long terminal repeat were inducible for Rep78 and Rep68 or CAT expression, respectively, when cotransfected with a plasmid containing the HIV-1 tat gene (pARtat). When equivalent amounts of pHIVrep and pBennCAT were cotransfected with increasing amounts of pARtat, expression of CAT activity was decreased. The pHIVrep construct was more inhibitory than plasmids expressing rep from the wild-type AAV2 p5 transcription promoter. rep expression from pHIVrep almost completely inhibited the replication of an HIV-1 proviral clone as measured by reverse transcriptase activity and p24 protein levels. Inhibition of HIV-1 production by Rep protein was also seen at the transcriptional level in that all HIV-1 transcripts were decreased when pHIVrep was present. The inhibitory effects of pHIVrep appear to be mediated primarily by Rep78 and perhaps Rep68. These results suggest that a trans-acting protein from a heterologous virus might be used to inhibit HIV-1 growth.
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PMID:Adeno-associated virus Rep protein inhibits human immunodeficiency virus type 1 production in human cells. 184 99

HIV-1 replication depends on the expression of trans-regulatory genes (tat, rev) encoded in the 3' part of the retroviral genome. HIV-1 Rev trans-activator protein allows the cytoplasmic translocation of incompletely spliced retroviral mRNA which is required for the translational switch from regulatory (Tat, Rev, Nef) to structural proteins (Gag, Pol, Env). The HIV-1 Rev regulatory protein comprises an activation domain (RAD) and a RNA binding domain (RBD). Both functional domains are not well defined and the RBD appears to overlap with the nuclear localization signal (NLS). Our mutational analysis localized the Rev protein domain important for RRE (nucleotide 7781 to 8000) binding in vitro to amino acid residues 31 to 50. Mutations in this domain always resulted in exclusion from the nucleoli. Furthermore, these mutants did not support Rev-dependent p24 Gag production in vivo. Sequences immediately upstream of this domain (RevM4, RevM19) were attenuated in their in vivo activity possibly indicating a role in Rev protein oligomerization. The observed tight correlation between subcellular localization and RNA binding in vitro indicates that this short stretch of amino acids supports two essential functions required for HIV-1 replication.
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PMID:Mutational analysis of functional domains in the HIV-1 Rev trans-regulatory protein. 185 65

Substantial evidence indicates that HIV-1 trans-activation by tat protein is mediated through the TAR RNA element. This RNA forms a stem-loop structure containing a three-nucleotide bulge and a six-nucleotide loop. Previous mutagenic analysis of TAR indicates that the bulge residues and a 4 bp segment of the stem constitute, in part, the tat binding site. However, there appears to be no sequence-specific contribution of the six-base loop. We have employed a ribonuclease protection technique to explore the interaction of tat with single-stranded regions of TAR. The results indicate that tat interacts with both the bulge and loop regions of TAR. Treatment of TAR RNA with RNase A results in cleavage at U23 and U31, located in the bulge and loop regions, respectively. High concentrations (approximately 2 microM) of Escherichia coli derived tat protein, prepared by standard procedures, gave complete protection of TAR RNA from RNase A cleavage. However, under these conditions, truncated TAR derivatives in which no stem-loop structure is expected to form were also protected, indicating nonspecific binding. In order to obtain a tat preparation with enhanced specificity toward TAR RNA, methods were developed for refolding the recombinant protein. This treatment enhanced the affinity of tat for TAR by approximately 30-fold [Kd(apparent) less than 25 nM] and markedly increased its specificity for the TAR. Again, tat protected TAR RNA from RNase A cleavage at both U23 and U31. Protection was also observed with RNase T1 which cleaves TAR RNA at three G residues in the six-base loop.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Refolded HIV-1 tat protein protects both bulge and loop nucleotides in TAR RNA from ribonucleolytic cleavage. 186 81

HTLV-I, II, HIV-1, 2 and other retroviruses possess genes for the transcriptional activators, tax and tat, the expression of which is closely related with the pathogenesis of leukemia and human immunodeficiency syndrome (AIDS) and induced by the virus infection. The effects of these activators on the expression of host cell genes, however, are still largely unknown. Recently the authors have discovered that infection with HIV or Mo-MuLV causes a specific acceleration of the synthesis of an UAG suppressor glutamine tRNA in the host cell; they could demonstrate that this phenomenon is based on transcriptional promotion of tRNA genes which is due to a new transcriptional activator synthesized as a function of viral infection and/or increased virus levels. The present paper discusses the significance of the suppressor tRNA and explains the role of the virus in the regulation of its expression.
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PMID:Cell biological aspects of HIV-1 infection: effect of the anti-HIV-1 agent Avarol. 189 96

Human immunodeficiency virus type 1 (HIV-1) primarily infects CD4+ lymphocytes and macrophages and causes AIDS in humans. Retroviral vectors allowing neomycin phosphotransferase (npt) gene expression were engineered to express 5' sequences of HIV-1 RNA in the antisense or sense orientation and used to transform the human CD4+ lymphocyte-derived MT4 cell line. Cells expressing antisense or sense RNA to the HIV-1 tat mRNA leader sequence, as part of the 3' untranslated region of the npt mRNA, remained sensitive to HIV-1 infection. In contrast, resistance to HIV-1 infection was observed in cells expressing antisense RNA to the HIV-1 primer-binding site or to the region 5' to the primer-binding site as part of the 3' region of the npt mRNA. Cells expressing the tat mRNA leader sequence in the sense orientation as a precise replacement of the 5' untranslated region of npt mRNA were also resistant to HIV-1. These results indicate that sense and antisense approaches can be used to interfere with HIV-1 multiplication.
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PMID:Inhibition of human immunodeficiency virus type 1 multiplication by antisense and sense RNA expression. 189 1


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