Jembrana disease virus Tat can regulate human immunodeficiency virus (HIV)long terminal repeat-directed gene expression and can substitute for HIV Tat in viral replication

Jembrana disease virus (JDV) is a bovine Lentivirus genetically similar to bovine immunodeficiency virus; it causes an acute and sometimes fatal disea se in infected animals. This virus carries a very potent Tat that can stron gly activate not only its own long terminal repeat (LTR) but also the human immunodeficiency virus (HIV) LTR. In contrast, HIV Tat cannot reciprocally activate the JDV LTR (H. Chen, G. E, Wilcox, G. Kertayadnya, and C. Wood, J. Virol. 73:658-666, 1999). This indicates that in transactivation JDV Tat may utilize a mechanism similar to but not the same as that of the HIV Tat . To further study the similarity of JDV and HIV tat in transactivation, we first tested the responses of a series of HIV LTR mutants to the JDV Tat. Cross-transactivation of HIV LTR by JDV Tat was impaired by mutations that disrupted the HIV type 1 transactivation response element (TAR) RNA stem-lo op structure. Our results demonstrated that JDV Tat, like HIV Tat, transact ivated the HIV LTR at least partially in a TAR-dependent manner. However, t he sequence in the loop region of TAR was not as critical for the function of JDV Tat as it was for HIV Tat. The competitive inhibition of Tat-induced transactivation by the truncated JDV or HIV Tat, which consisted only of t he activation domain, suggested that similar cellular factors were involved in both JDV and HIV Tat-induced transactivation. Based on the one-round tr ansfection assay with HIV tat mutant proviruses, the cotransfected JDV tat plasmid can functionally complement the HIV tat defect. To further characte rize the effect of JDV Tat on HIV, a stable chimeric HIV carrying the JDV t at gene was generated. This chimeric HIV replicated in a T-cell line, C8166 , and in peripheral blood mononuclear cells, which suggested that JDV Tat c an functionally substitute for HIV Tat. Further characterization of this ch imeric virus will help to elucidate how JDV Tat functions and to explain th e differences between HIV and JDV Tat transactivation.