A TRANSFORMING FRAGMENT WITHIN THE DIRECT REPEAT REGION OF HUMAN HERPESVIRUS TYPE-6 THAT TRANSACTIVATES HIV-1

HHV-6 infection has been associated with several malignancies includin g non-Hodgkin's lymphoma and Hodgkin's disease by the presence of high antibody titer and/or the presence of HHV-6 DNA. To understand their oncogenic potential, SalI restriction fragments from HHV-6 strain U110 2 were transfected into NIH3T3 cells to assess transforming ability. A 3.9-kbp SalI-L DNA fragment spanning the junction of the direct repea t left (DR(L)) and unique long segment (U(L)) regions of HHV-6 induced foci of morphologically altered cells. The SalI-L transformed NIH3T3 focal lines induced tumors in nude mice within 2 weeks. The retention of HHV-6 specific DNA observed in SalI-L transformed cells and their t umor-derived lines suggest a possible maintenance function. Since both HHV-6 infection as well as transforming fragments from other DNA viru ses have been shown to transactivate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR), SalI-L was examined for tra nsactivation activity. SalI-L up-regulated HIV-1 LTR CAT 10-15 fold in both monkey CV-1 and human T Jurkat cells. The further study of the S alI-L transforming fragment exhibiting transactivation of HIV-1 LTR wi ll elucidate whether these two activities are encoded by a single gene and will aid in the understanding of the interaction between HHV-6 an d HIV-1 as it relates to progression of AIDS and/or AIDS-related malig nancies.