title: Rhesus monkey TRIM5α represses HIV-1 LTR promoter activity by negatively regulating TAK1/TAB1/TAB2/TAB3-complex-mediated NF-κB activation.
abstract: TRIM5α has been identified as the main restriction factor responsible for resistance of Old World monkey cells to HIV-1 infection. The precise mechanism of viral inhibition by TRIM5α remains elusive but appears to occur in multiple ways. Here, we report that rhesus monkey TRIM5α (TRIM5α(rh)) can represses HIV-1 LTR promoter activity by negatively regulating TAK1/TAB1/TAB2/TAB3-complex-mediated NF-κB activation when TRIM5α(rh) is overexpressed. We show that the overexpressed TRIM5α(rh) can interact with the TAK1/TAB1/TAB2/TAB3 complex by binding to TAB1 and promotes the degradation of TAB2 within the complex via the lysosomal degradation pathway. Subsequently, TRIM5α(rh) lowers the IKKα protein level and inhibits NF-κB p65 phosphorylation, and knockdown of TRIM5α(rh) expression by small interfering RNA in TRIM5α(rh)-overexpressing cells can abolish this inhibition. Finally, the inhibition of p65 phosphorylation results in the repression of HIV-1 LTR promoter activity. Taken together, these findings indicate that TRIM5α(rh) plays a previously unrecognized role in repressing HIV-1 transcription by inhibiting TAK1/TAB1/TAB2/TAB3-complex-mediated NF-κB activation when TRIM5α(rh) is overexpressed.
authors.affiliation: The State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Xiaohongshan 44, Wuhan 430071, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gong
authors.forename: Xi-Hui
authors.initials: XH
authors.lastname: Shen
authors.forename: Hui
authors.initials: H
authors.lastname: Qiu
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.forename: Rong-Ge
authors.initials: RG
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D008253:Macaca mulatta; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016328:NF-kappa B; D020930:MAP Kinase Kinase Kinases