| Popis: |
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. |
