Effect of glucocorticoids on chronic human immunodeficiency virus (HIV) infection and HIV promoter-mediated transcription.
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.
Laurence
J
J
Department of Medicine, Cornell University Medical College, New York, NY 10021.
Sellers
M B
MB
Sikder
S K
SK
D000163:Acquired Immunodeficiency Syndrome / Q000382:microbiology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006678:HIV / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D007065:Idoxuridine / Q000494:pharmacology; D066298:In Vitro Techniques; D011241:Prednisone / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011696:Purpura, Thrombocytopenic / Q000150:complications; D011961:Receptors, Fc / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D011961:Receptors, Fc; D003907:Dexamethasone; D007065:Idoxuridine; D013755:Tetradecanoylphorbol Acetate; D011241:Prednisone