HIV type 1 Tat inhibits tumor necrosis factor alpha-induced repression of tumor necrosis factor receptor p55 and amplifies tumor necrosis factor alpha activity in stably tat-transfected HeLa cells

Citation
C. Chiao et al., HIV type 1 Tat inhibits tumor necrosis factor alpha-induced repression of tumor necrosis factor receptor p55 and amplifies tumor necrosis factor alpha activity in stably tat-transfected HeLa cells, AIDS RES H, 17(12), 2001, pp. 1125-1132
Citations number
52
Categorie Soggetti
Immunology
Journal title
AIDS RESEARCH AND HUMAN RETROVIRUSES
ISSN journal
08892229 → ACNP
Volume
17
Issue
12
Year of publication
2001
Pages
1125 - 1132
Database
ISI
SICI code
0889-2229(20010810)17:12<1125:HT1TIT>2.0.ZU;2-T
Abstract
The human immunodeficiency virus type 1 (HIV-1) Tat protein is a key regula tory protein in the HIV-1 replication cycle. Tat interacts with cellular tr anscriptional factors and cytokines, such as tumor necrosis factor (TNF-alp ha), and alters the expression of a variety of genes in HIV-1-infected and noninfected cells. To further elucidate the mechanisms by which HIV-1 Tat a mplifies the activity of TNF-alpha, we transfected the HIV-1 tat gene into an epithelial (HeLa) cell line. We observed that Tat-expressing cells had i ncreased NF-kappaB-dependent trans-activational activity due to enhanced NF -kappaB-DNA binding in response to TNF-alpha treatment. Tumor necrosis fact or receptor (TNFR) p55 was the prominent receptor, as neutralizing antibodi es to TNFR p55, but not to TNFR p75, blocked TNF-alpha -mediated NF-kappaB activation. Furthermore, tat-transfected cells were more sensitive to TNF-a lpha -induced. cytotoxicity and only the neutralizing antibodies to TNFR p5 5 completely protected the cells. To determine whether TNFR p55 was involve d in amplification of cellular response to TNF-alpha by HIV-1 Tat, we inves tigated the effect of TNF-alpha on TNFR p55 expression in the tat-transfect ed cells. TNF-alpha treatment resulted in a reduction in both TNFR p55 mRNA and protein levels in the control cells but not in the tat-transfected cel ls as determined with Northern blot and Western blot analyses, respectively . Our results indicate that HIV-1 Tat may inhibit TNF-alpha -induced repres sion of TNFR p55 and thereby amplify TNF-alpha activity in these stably tra nsfected cells.