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

TRIM5 alpha 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 TRIM5 alpha remains elusive but appears to occur in multiple ways. Here, we report that rhesus monkey TRIM5 alpha (TRIM5 alpha(rh)) can represses HIV-1 LTR promoter activity by negatively regulating TAK1/TAB1/TAB2/TAB3-complex-mediated NF-kappa B activation when TRIM5 alpha(rh) is overexpressed. We show that the overexpressed TRIM5 alpha(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, TRIM5 alpha(rh) lowers the IKK alpha protein level and inhibits NF-kappa B p65 phosphorylation, and knockdown of TRIM5 alpha(rh) expression by small interfering RNA in TRIM5 alpha(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 TRIM5 alpha(rh) plays a previously unrecognized role in repressing HIV-1 transcription by inhibiting TAK1/TAB1/TAB2/TAB3-complex-mediated NF-kappa B activation when TRIM5 alpha(rh) is overexpressed.