Heat shock induction of HIV production from chronically infected promonocytic and T cell lines.
HIV infection is associated with a long period of clinical latency before the development of symptoms and HIV-related disease. Two chronically HIV-infected cell lines, U1 (promonocytic) and ACH-2 (T-lymphocytic) have been developed as models for studying the mechanisms governing viral latency and the reactivation of virus expression. We have previously shown that a variety of physiologic stimuli, including cytokines and cell stress, can up-regulate HIV expression from these cell lines. In this study we demonstrate that heat shock can also up-regulate the production of virus from both ACH-2 and U1 cells. Heat induction of virus appears to be mediated at the transcriptional level as established in long terminal repeat-chloramphenicol acetyl transferase transient transfection experiments with the use of U937 cells. This inductive effect in part requires the NF-kappa B-binding region of the HIV-long terminal repeat. Furthermore, although physiologic levels of heat are not sufficient to directly induce virus production from these cells, these temperatures are able to synergistically enhance virus production in U1 cells stimulated with IL-6 and granulocyte macrophage-CSF. In contrast, the inductive effect of other cytokines (i.e., TNF-alpha) was not affected by heat stimulation. These in vitro observations suggest that the hyperthermia associated with opportunistic infections, particularly in conjunction with certain cytokines that are released during immune reactions, may play a role in the in vivo induction of HIV expression in infected cells.
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
S K
SK
Stanley
P B
PB
Bressler
G
G
Poli
A S
AS
Fauci
D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006678:HIV / Q000254:growth & development* / Q000472:pathogenicity; D006358:Hot Temperature; D015850:Interleukin-6 / Q000494:pharmacology; D012367:RNA, Viral / Q000096:biosynthesis; D012194:RNA-Directed DNA Polymerase / Q000096:biosynthesis; D051381:Rats; D012091:Repetitive Sequences, Nucleic Acid; D012191:Retroviridae Proteins / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000382:microbiology*; D014158:Transcription, Genetic; D014775:Virus Activation
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D015850:Interleukin-6; D012367:RNA, Viral; D012191:Retroviridae Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015500:Chloramphenicol O-Acetyltransferase; D012194:RNA-Directed DNA Polymerase