Inhibition of HIV-1 latency reactivation by dehydroepiandrosterone (DHEA) and an analog of DHEA.
The initial infection with human immunodeficiency virus type 1 (HIV-1) in most individuals usually results in the establishment of a latent or chronic infection before eventual progression toward acquired immunodeficiency syndrome. HIV-1 can also establish a latent or persistent infection in some T cell lines that show minimal constitutive virus expression. However, activation of the T cell lines leading to enhanced HIV-1 replication can be induced by antigens, mitogens, and cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin 1, and interleukin-2). Various gene products from other viruses (HTLV-1, HSV, EBV, CMV, HBV, and HHV-6) can also enhance HIV-1 long terminal repeat (LTR)-driven reporter gene activity. On the basis of these observations, it has been proposed that reactivation of latent HIV-1 harbored in chronically infected T lymphocytes, monocytes, or macrophages plays an important role in the pathogenesis of AIDS. So far, there are no drugs or therapy available that can provide protection against HIV-1 latency reactivation. ACH-2, derived from a human T cell line (CEM), is chronically infected with HIV-1, with low levels of constitutive virus expression. ACH-2 can be converted to productive infection by stimulation of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), mitogen or cytokines (TNF-alpha), or infection with HSV. Therefore the ACH-2 cell line is a good candidate for studying the effects of drugs on HIV-1 activation. Previously, we have reported that DHEA and synthetic analogs of DHEA can be modest inhibitors of HIV-1 IIIB replication in phytohemagglutinin-stimulated peripheral blood lymphocyte cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
Yang
J Y
JY
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Schwartz
A
A
Henderson
E E
EE
D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004279:DNA, Viral; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000494:pharmacology*; D004790:Enzyme Induction; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D012194:RNA-Directed DNA Polymerase / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000382:microbiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014775:Virus Activation / Q000187:drug effects*; D017735:Virus Latency / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D004279:DNA, Viral; D016328:NF-kappa B; D003687:Dehydroepiandrosterone; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D013755:Tetradecanoylphorbol Acetate