Publication Date:
1987-12-11
Description:
To investigate the mechanism by which immune activation augments replication of the human immunodeficiency virus type 1 (HIV-1) in infected T cells, four different classes of T cell mitogens were evaluated for their effects on the HIV-1 long terminal repeat (LTR). Phytohemagglutinin (PHA), a mitogenic lectin; phorbol 12-myristic 13-acetate, a tumor promoter; ionomycin, a calcium ionophore; and tat-1, the trans-activator protein from the human T cell leukemia/lymphoma virus type I (HTLV-I) each stimulated the HIV-1 LTR. Studies of deleted forms of the LTR supported a central role in these responses for the HIV-1 enhancer, which alone was sufficient for mitogen inducibility, but also suggested that other 5' positive and negative regulatory elements contribute to the overall magnitude of the response. Synergistic activation of the HIV-1 LTR (up to several thousandfold) was observed with combinations of these mitogens and the HIV-1--derived tat-III protein. Cyclosporin A, an immunosuppressive agent, inhibited PHA-mediated activation of the HIV-1 LTR but was without effect in the presence of other mitogens. Thus, HIV-1 gene expression and replication appear to be regulated, via the HIV-1 LTR, by the same mitogenic signals that induce T cell activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Siekevitz, M -- Josephs, S F -- Dukovich, M -- Peffer, N -- Wong-Staal, F -- Greene, W C -- New York, N.Y. -- Science. 1987 Dec 11;238(4833):1575-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Duke University School of Medicine, Durham, NC 27710.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2825351" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Line
;
Cyclosporins/pharmacology
;
Deltaretrovirus/*physiology
;
Genes, Viral
;
HIV/drug effects/genetics/*growth & development
;
Mitogens/*pharmacology
;
Retroviridae Proteins/*physiology
;
T-Lymphocytes/*immunology
;
Trans-Activators
;
Transcription Factors/*physiology
;
Transcription, Genetic
;
*Virus Activation/drug effects
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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