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

A new method is described for the direct construction of randomly mutagenized genes by applying the polymerase chain reaction (PCR) to an oligonucleotide synthesized using doped nucleotide reservoirs. We have demonstrated the utility of this method by generating a library of mutant HIV-1 tat genes. Several arbitrarily selected, inactive tat clones were sequenced to evaluate the extent of the mutagenesis. Moreover, fourteen recombinants encoding varying levels of transcriptional trans-activator activity were isolated by transient transfection of sub-library pools into a HeLa cell line bearing an HIV-LTR-chloramphenicol acetyltransferase (CAT) reporter gene. Sequence data revealed a spectrum of alterations including nucleotide substitutions, insertions, and deletions, suggesting that mutations arose from both the doped DNA synthesis and the subsequent PCR 'rescue' of full-length product. Sequence comparison between inactive and active Tat clones revealed a selection pressure against amino-acid substitutions within the N-terminal domains of Tat, indicating the importance of this region to trans-activation competence. In addition, single and double missense mutations within the basic-rich, TAR RNA-binding domain were seen to be tolerated within active Tat clones.
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PMID:Random mutagenesis of the human immunodeficiency virus type-1 trans-activator of transcription (HIV-1 Tat). 143 50

We have shown previously that HIV-1 matrix protein p17 is transported to the nucleus of Jurkat-tat and H9 cells soon after infection. As shown in this combination, gag polyprotein p55 synthesized 48 h after cell infection is cleaved in cytosol rapidly after its synthesis, and nascent p17 enters the nuclei and gradually accumulates there. Uncleaved p55 molecules and intermediate precursors are rapidly transported to the membranes and are also found in nuclei. Mature gag proteins are seen in membranes only after prolonged period of labelling or chase (4 or more hours later). To determine whether the nascent p17 is associated with viral genomic RNA in the nuclei, the cells were fractionated, the viral complexes were immunoprecipitated by monoclonal antibodies (MAbs) against gag proteins, and RNA was extracted and analyzed by slot and blot hybridization. MAb against p17 precipitated all the viral RNA from the nuclei including full-size genomic RNA and essential parts from membranes while MAb against p24 did not precipitate any viral RNA from the nuclei. These data suggest that matrix protein is linked to genomic RNA in the nuclei and raise the possibility that p17 may transfer viral nucleocapsids from the nuclei to plasma membranes, the site of virus assembly.
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PMID:HIV-1 matrix protein p17 resides in cell nuclei in association with genomic RNA. 145 92

HIV-2ALT is a highly divergent HIV-2-related isolate that is genetically equidistant to the prototypic HIV-2 strains, defined by HIV-2ROD, and to the simian immunodeficiency viruses SIVmac and SIVsm. We have now cloned and sequenced the envelope region of HIV-2ALT, thus completing the analysis of the whole viral genome. The sequences of env and nef and of the second exons of tat and rev were compared with those of the other viruses of the HIV-2/SIVsm/SIVmac group. Despite of the high degree of variation of HIV-2ALT, functional domains of the genes are conserved. Although in env, the overall pattern of constant and variable domains is maintained, many single amino acid exchanges exist at positions previously thought to be constant in HIV-2 strains. In addition, when compared with a broader spectrum of immunodeficiency viruses, which includes SIVMND from mandrill and SIVAGM from African green monkey, HIV-2ALT Env has a high percentage of amino acid exchanges, which are unique to this strain. This underlines the separate branch of HIV-2ALT within the phylogenetic tree and makes obvious the inclusion of such divergent strains in preventive and therapeutic programs.
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PMID:Analysis of the envelope region of the highly divergent HIV-2ALT isolate extends the known range of variability within the primate immunodeficiency viruses. 145 8

Individuals infected with HIV (Human Immunodeficiency Virus) frequently develop B cell non-Hodgkins lymphoma. Although previous studies have failed to document the presence of HIV sequences in these tumors, the recent demonstration of malignant transformation of primary B lymphocytes by HIV-1 has prompted us to reinvestigate this issue. We have examined DNA extracted from 7 lymphomas and 5 lymphadenopathy specimens for HIV LTR (long terminal repeat), gag, and tat sequences using the polymerase chain reaction (PCR). All samples produced products of the expected size with primers for these regions, indicating the presence of HIV proviral sequences in these tissues. The amount of provirus in the tissue was estimated by normalizing the amount of HIV product to the amount of product for the cellular myc gene or beta globin gene. Products were quantitated during the exponential phase of DNA accumulation. These studies indicated that provirus was present at approximately one copy per cell in the 7 lymphoma samples and in 4 of the 5 lymphadenopathy samples. These results are consistent with a direct role for virus in the initiation of lymphoma. Studies to determine whether provirus resides in the lymphoma cells per se will be necessary to further substantiate this hypothesis.
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PMID:Does HIV infection of B lymphocytes initiate AIDS lymphoma? Detection by PCR of viral sequences in lymphoma tissue. 149 Mar 78

We have developed a binary transgenic mouse system that allows easy in vivo evaluation of new anti-human immunodeficiency virus type 1 (HIV-1) drugs or therapies specifically designed to target the viral transactivator protein (TAT) or long terminal repeat (LTR) functions. This approach consists of a simple genetic cross between an "activator" transgenic mouse expressing the HIV-1-tat gene exclusively to T lymphocytes and a "target" transgenic mouse bearing a silent reporter gene whose expression is under the control of the HIV-1-LTR. As expected, most of the target transgenic animals did not express the reporter gene; on the contrary, all the double-transgenic mice bearing both the activator and target transgenes strongly expressed the TAT-induced reporter gene. The choice of a secreted human alpha 1-antitrypsin variant (alpha 1-AT) as reporter gene readily permits in a single animal the quantitative determination of the plasma level of alpha 1-AT protein before and after anti-LTR or anti-TAT treatments. Such mice may be valuable as new laboratory models for the in vivo evaluation of agents with potential anti-HIV-1 activity.
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PMID:A novel transgenic mouse model for the in vivo evaluation of anti-human immunodeficiency virus type 1 drugs. 149 46

Human immunodeficiency virus type 1 (HIV-1) proviral mutants that lack viral regulatory genes are unable to replicate unless rescued by complementation in trans. Structurally intact virus can be produced by infecting recombinant cell lines expressing the deficient genes. A HIV-1 mutant functionally defective in tat and rev (vIIIB delta Tat/Rev), which replicates only in a recombinant T-cell line expressing tat and rev (CEMTART), is described in this report. Infection of the CEMTART cell line with vIIIB delta Tat/Rev permits the complete HIV-1 life cycle, including cytopathology, decreased expression of CD4, and production of viral structural proteins, to be biologically contained. Culture supernatants from infected CEMTART contain virus that is able to replicate only in uninfected CEMTART. No reversion of vIIIB delta Tat/Rev to wild-type HIV-1 was observed as measured either by sequencing proviral vIIIB delta Tat/Rev or by detecting the ability of vIIIB delta Tat/Rev to replicate in CEM or activated CD4-bearing T lymphocytes. Defective HIV-1 mutants produced by trans complementation of essential genes permit infection and analysis of defined genotypes on cellular function and phenotype. Authentic HIV-1 structural proteins and infected cells can be prepared in mass, and agents that interfere with the HIV-1 life cycle can be studied on a large scale with minimum risk of exposing workers to virulent HIV-1.
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PMID:Derivation of a biologically contained replication system for human immunodeficiency virus type 1. 150 83

A ribozyme was constructed that specifically cleaves RNA that contains the first coding exon of the tat gene of HIV-1. This anti-tat ribozyme was incorporated into a Moloney murine leukemia virus vector. A sequence containing only the 48-nucleotide antisense region of the ribozyme was also inserted into the retroviral vector. Human T-cell lines constitutively producing the tat-antisense and the anti-tat ribozyme RNA were created by transduction into Jurkat cells. When challenged with HIV-1, both the tat-antisense and anti-tat ribozyme-producing cells inhibited the replication of HIV-1. The antisense vector conferred a greater resistance to HIV-1 replication than did the anti-tat ribozyme vector.
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PMID:Inhibition of replication of HIV-1 by retroviral vectors expressing tat-antisense and anti-tat ribozyme RNA. 152 27

In this report we show that signals for transcriptional factors are not restricted to the HIV-1 LTR, but are present throughout the HIV-1 genome. Furthermore, we identified a sequence, AGAACAGATG, highly homologous to the X-box of class II MHC genes and located within the tat-IVS/env region of HIV-1. Double stranded oligonucleotides mimicking the HIV-1 region containing AGAACAGATG were synthesized and band shift experiments were performed demonstrating that this HIV-1 genomic region binds nuclear proteins. We further demonstrate that the binding of nuclear factors to this tat-IVS/env HIV-1 sequence is competed for, in the band-shift assay, by the highly homologous X-box of the promoter of the human HLA-DR alpha gene. The presence in the HIV-1 genome of DNA sequences homologous or identical to regulatory sequences of cellular genes represents a potential mechanism of predation of DNA elements recognized by DNA binding proteins.
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PMID:DNA elements target of transcriptional factors are not restricted to long terminal repeat of human immunodeficiency virus. 156 83

The etiologic agent of the acquired immunodeficiency syndrome is a retrovirus included in the subclass of lentiviruses in view of certain characteristics common to these viruses. Their similarity is mainly represented by the extreme slowness of disease manifestation and by the fact that HIV, like other lentiviruses, spreads within the organism in spite of an immune reaction. The mechanism of replication is not dissimilar to that of other retroviruses except for the expression of a particularly large number of regulating genes the most important of which are called tat, rev, and nef. Further genes with a probable regulating function are nef, vpr, and vpx. In the field of diagnostic virology, together with normal isolation tests, a technique that has become particularly important is PCR (polymerase chain reaction) which allows to obtain a relevant amount of specific viral DNA sequences by the use of a DNA polymerase and specific primers.
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PMID:[Acquired immunodeficiency virus (HIV-1). Biological aspects and virological diagnosis]. 156 59

Antisense oligodeoxynucleotide (ODN), which are directed against the splice acceptor site of exon II of the regulatory gene tat of the human immunodeficiency virus type 1 (HIV-1), have been described. These 20-mer ODN's displayed moderate anti-HIV activity in vitro. Using the same antisense ODN (termed ODN-2), which was additionally modified and protected both at the 3'- and the 5'-terminus by two phosphorothioate internucleotide linkages, a strong anti-HIV activity (EC50: 2.7 micrograms/ml) could be measured in the HIV-1/CEM- and HIV-1/HeLa-T4+ cell system. The analogous ODNs which were protected only at one end were either inactive (up to 10 micrograms/ml) or displayed a low antiviral activity. Time kinetic studies revealed that the antisense ODN-2 reduced the release of HIV-1 already after an incubation time of 1 h. By applying S1 nuclease protection procedures, it could be established that the antisense ODN-2 inhibited splicing of high molecular weight transcript to the 2-kb tat mRNA in HIV-1-infected CEM cells. Transfection experiments with pU3R-III chloramphenicol acetyltransferase expression vector in HeLa-T4+ cells revealed that the antisense ODN-2 blocked the Tat protein-mediated transactivation process. In co-transfection experiments using pSV2tat72 or scrape loading studies with purified Tat, the transactivation was restored. These data indicate that the selected antisense ODN-2 displays its anti-HIV effect by blocking the splicing process leading to the functional 2-kb tat mRNA.
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PMID:Antisense oligodeoxynucleotide: inhibitor of splicing of mRNA of human immunodeficiency virus. 156 36


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