GENETIC REGULATION OF HIV BY DNA VIRUS TRANS-ACTING PROTEINS AND SODIUM BUTYRATE

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

GENETIC REGULATION OF HIV BY DNA VIRUS TRANS-ACTING PROTEINS AND SODIUM BUTYRATE

Diss Abstr Int [B]; 50(1):61 1989. Unique Identifier : AIDSLINE ICDB/90658129
Bohan CA; Emory Univ.

Abstract: Gene expression of HIV-1, the etiological agent of AIDS, has been shown to be regulated by HIV-1 nonstructural regulatory polypeptides and by chemical and DNA virus modulators. Using a transient expression system, the herpes simplex virus (HSV) ICP4, human cytomegalovirus (HCMV) IE1, adenovirus (Ad) E1A 13S gene products, and sodium butyrate were demonstrated to transactivate HIV-1 long terminal repeat (LTR) promoter activity in a specific manner and in numerous human cell types; HSV ICPO and HCMV IE2 transactivated HIV-1 LTR-directed gene expression but lacked target promoter specificity. In contrast, the Ad E1A 12S gene product repressed HIV-1 gene expression. These viral and chemical effector molecules manifested their transcriptional effects by interacting with HIV-1 LTR regulatory domains and their associated cellular transcription factors as discerned by LTR deletion and site-directed mutant analysis. These effector molecules affected HIV-1 replication and production in the presence of HIV-1 gene products as measured by reverse transcriptase assays. In addition, these DNA virus gene products and sodium butyrate were found to stimulate HIV-2 LTR-directed gene expression. HIV-1 and HCMV gene products were detected in brain cells of AIDS patients by immunoperoxidase analysis and in situ hybridization. These experimental results have led to the conclusion that DNA viruses, especially HCMV, may be active cofactors in AIDS pathogenesis by modulating HIV-1 gene expression. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD89-08014)

Keywords: Acquired Immunodeficiency Syndrome/MICROBIOLOGY Adenoviruses, Human/GENETICS Butyric Acids/*PHARMACOLOGY Cytomegalovirus/GENETICS Gene Expression Regulation, Viral/*DRUG EFFECTS Gene Products, rev/*GENETICS Human HIV-1/*GENETICS HIV-2/*GENETICS Simplexvirus/GENETICS Terminator Regions (Genetics)/DRUG EFFECTS Virus Replication/*DRUG EFFECTS THESIS
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M9120726

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