HIV-1 tat gene induces tumor necrosis factor-beta (lymphotoxin) in a human B-lymphoblastoid cell line.
The tat protein from human immunodeficiency virus type 1 (HIV-1) activates viral gene expression and is essential for HIV replication in vitro. It has also been shown that the tat gene product specifically inhibits antigen-induced proliferation of human peripheral blood lymphocytes. In order to understand the growth and immunomodulatory roles of HIV-1 tat, we have examined the effect of the tat gene on the expression of tumor necrosis factors in a human B-lymphoblastoid cell line (Raji). We report here that the HIV-1 tat gene introduced into Raji cells by retroviral-mediated transformation induces production of tumor necrosis factor-beta (TNF-beta). The tat-mediated induction of TNF-beta seems to be both at the transcriptional and post-transcriptional levels because, concurrent with a 30-fold increase in the levels of TNF-beta protein, an approximate 8-fold increase in mRNA was observed in tat-transformed Raji cells. It is recently reported that tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients (Ensoli, B., Barillari, G., Salahuddin, S.Z., Gallo, R.C., and Wong-Staal, F. (1990) Nature 345, 84-86). Since TNF has been shown to function as a growth factor for several cell types, our results showing induction of TNF-beta by tat indicate the possibility that a growth-stimulatory role of HIV-1 tat on Kaposi's sarcoma cells is mediated through TNF-beta.
Sastry
K J
KJ
Department of Molecular Pathology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Reddy
H R
HR
Pandita
R
R
Totpal
K
K
Aggarwal
B B
BB
D001402:B-Lymphocytes; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D015756:Genes, tat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008233:Lymphotoxin-alpha / Q000096:biosynthesis / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D008233:Lymphotoxin-alpha; D015500:Chloramphenicol O-Acetyltransferase