Hepatitis C virus core protein inhibits human immunodeficiency virus type 1 replication.
We previously demonstrated that hepatitis C virus (HCV) core protein is a strong repressor of human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) basal transcription. In this study, we have localized the HCV core protein-response domain to a region between nucleotides -65 and +3 within the HIV-LTR. Thus, neither the upstream negative regulatory elements, or binding sites for various transcription factors (e.g. NF-kappa B, USF-1, IL2/IL-2R) nor the downstream TAR regions were involved in HCV core-mediated repression. HCV core protein mediated repression of the basal transcriptional activity of HIV-1 LTR was abrogated by the Tat protein. Furthermore, HeLa-T4 cells expressing HCV core protein showed inhibition of HIV-1 replication after acute infection with cell-free HIV. A similar observation was also noted in CD4+ and CD4-lymphocytic cell lines cotransfected with an infectious 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 transcription and modulate viral replication.
Division of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
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Srinivas
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Ray
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Meyer
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D019380:Anti-HIV Agents / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D016655:HIV Core Protein p24 / Q000378:metabolism; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006367:HeLa Cells; D016174:Hepacivirus; D006801:Humans; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus