Rhesus monkey TRIM5α represses HIV-1 LTR promoter activity by negatively regulating TAK1/TAB1/TAB2/TAB3-complex-mediated NF-κB activation

Arch Virol. 2011 Nov;156(11):1997-2006. doi: 10.1007/s00705-011-1097-6. Epub 2011 Sep 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Line
  • Down-Regulation*
  • HIV Infections / genetics
  • HIV Infections / metabolism*
  • HIV Infections / virology
  • HIV Long Terminal Repeat*
  • HIV-1 / genetics*
  • HIV-1 / physiology
  • Humans
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism*
  • Macaca mulatta
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Protein Binding
  • Signal Transduction

Substances

  • Adaptor Proteins, Signal Transducing
  • NF-kappa B
  • MAP Kinase Kinase Kinases