Effect of glucocorticoids on chronic human immunodeficiency virus (HIV) infection and HIV promoter-mediated transcription.

Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.

Effect of glucocorticoids on chronic human immunodeficiency virus (HIV) infection and HIV promoter-mediated transcription.

Blood. 1989 Jul;74(1):291-7. Unique Identifier : AIDSLINE MED/89323352
Laurence J; Sellers MB; Sikder SK; Department of Medicine, Cornell University Medical College, New; York, NY 10021.

Abstract: Corticosteroids are used in treatment of a variety of human immunodeficiency virus (HIV)-related disorders. Preliminary reports of a temporal relationship between administration of these drugs to viral carriers and development of AIDS raised the possibility that they can modify the course of HIV infection. Because glucocorticoids can alter specific gene expression in at least one immunosuppressive murine retrovirus, mammary tumor virus, we explored the ability of dexamethasone (DXM) to upregulate chronic HIV replication or to alter transcription at the HIV-1 long terminal repeat (LTR). A clone of promonocytic cells chronically infected with HIV-1 could be converted to a productive state of replication by phorbol ester or halogenated pyrimidine exposure, yet was unperturbed by DXM used over broad concentrations (10(-4) to 10(-9) mol/L) and time intervals (24 to 96 hours). This unresponsiveness corresponded to the lack of a positive effect of DXM on HIV associated trans-activation in both monocytic and CD4+ T cells. These cells possessed the appropriate steroid receptors, as DXM downregulated Fc gamma type-I receptors in both normal and HIV-infected promonocytic cells. In addition, DXM could block the transcriptional enhancement of an HIV-LTR-linked reporter gene by phorbol ester, while leaving basal levels of HIV-LTR-directed transcription unperturbed. These data are discussed in the context of clinical reviews of short-term steroid use in HIV-infected individuals.

Keywords: Acquired Immunodeficiency Syndrome/MICROBIOLOGY Cell Division/DRUG EFFECTS Cell Line Dexamethasone/*PHARMACOLOGY Gene Expression Regulation/*DRUG EFFECTS Human HIV/GROWTH & DEVELOPMENT/*GENETICS Idoxuridine/PHARMACOLOGY In Vitro Prednisone/PHARMACOLOGY Promoter Regions (Genetics) Purpura, Thrombocytopenic/COMPLICATIONS Receptors, Fc/METABOLISM Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Tetradecanoylphorbol Acetate/PHARMACOLOGY Transcription, Genetic/DRUG EFFECTS JOURNAL ARTICLE

891130
M89B0538

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