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
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
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.