Heat shock induces HIV-1 replication in chronically infected promyelocyte cell line OM10.1.
A long period of clinical latency before development of symptoms is characteristic of human immunodeficiency virus type 1 (HIV-1) infection. OM10.1, a promyelocyte cell line latently infected with HIV-1, has been developed as a model for studying the mechanism of viral latency and the activation of virus expression. We found that this latently infected cell line with heat shock at 42 degrees C for 2 h resulted in a high level of HIV-1 production without addition of any cytokines. The mechanism of activation was analyzed by using anti-TNF-alpha antibody and various inhibitors. Although the TNF-alpha level in culture supernatants was below the sensitivity of an ELISA assay system, addition of anti-TNF-alpha antibody in culture medium could partially suppress the heat shock induced HIV-1 production. Staurosporine (PKC inhibitor), pentoxifylline (NF-kappa B inhibitor), and Ro5-3335 (HIV-1 Tat inhibitor) also inhibited significantly the heat shock induced virus activation. In particular, staurosporine achieved approximately 90% inhibition of the HIV-1 antigen expression in heat shock-treated OM10.1 at a non-toxic concentration. Although the mechanism of HIV-1 activation with heat shock has not been fully elucidated yet, it is presumed PKC plays an important role in HIV-1 activation. Thus, the present observations will provide a further insight into the pathogenesis of HIV-1 infections.
Hashimoto
K
K
Department of Microbiology, Fukushima Medical College, Japan.
Baba
M
M
Gohnai
K
K
Sato
M
M
Shigeta
S
S
D000470:Alkaloids / Q000494:pharmacology; D000906:Antibodies / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015696:Gene Products, tat / Q000037:antagonists & inhibitors; D006098:Granulocytes / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D018869:Heat-Shock Response; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010431:Pentoxifylline / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology; D019311:Staurosporine; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014775:Virus Activation / Q000187:drug effects / Q000502:physiology; D054322:tat Gene Products, Human Immunodeficiency Virus
D000470:Alkaloids; D000906:Antibodies; D000998:Antiviral Agents; D001570:Benzodiazepinones; D004791:Enzyme Inhibitors; D015696:Gene Products, tat; D016328:NF-kappa B; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus; C072173:Ro 5-3335; D011493:Protein Kinase C; D019311:Staurosporine; D010431:Pentoxifylline