HEPATITIS-C VIRUS CORE PROTEIN INHIBITS HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION

We previously demonstrated that hepatitis C virus (HCV) core protein i s a strong repressor of human immunodeficiency virus type 1 (HIV-1) lo ng terminal repeat (LTR) basal transcription. In this study, we have l ocalized the HCV core protein-response domain to a region between nucl eotides -65 and +3 within the HIV-LTR. Thus, neither the upstream nega tive regulatory elements, or binding sites for various transcription f actors (e.g. NF-kappa B, USF-1, IL2/IL-2R) nor the downstream TAR regi ons were involved in HCV core-mediated repression. HCV core protein me diated repression of the basal transcriptional activity of HIV-1 LTR w as abrogated by the Tat protein. Furthermore, HeLa-T4 cells expressing HCV core protein showed inhibition of HIV-1 replication after acute i nfection with cell-free HIV. A similar observation was also noted in C D4(+) and CD4(-) lymphocytic cell lines cotransfected with an infectio us molecular clone of HIV-1 and the HCV core protein expression vector . Thus, a repression of basal transcription prior to the accumulation of threshold levels of Tat protein appears to restrict HIV-1 transcrip tion and modulate viral replication.