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

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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 (TRIM5αrh) can represses HIV-1 LTR promoter activity by negatively regulating TAK1/TAB1/TAB2/TAB3-complex-mediated NF-κB activation when TRIM5αrh is overexpressed. We show that the overexpressed TRIM5αrh 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, TRIM5αrh lowers the IKKα protein level and inhibits NF-κB p65 phosphorylation, and knockdown of TRIM5αrh expression by small interfering RNA in TRIM5αrh-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 TRIM5αrh plays a previously unrecognized role in repressing HIV-1 transcription by inhibiting TAK1/TAB1/TAB2/TAB3-complex-mediated NF-κB activation when TRIM5αrh is overexpressed.

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Acknowledgments

We thank Dr. Hong-Bing Shu (Wuhan University, Wuhan, China) for providing the Flag-TAB2 and Flag-TAB3 plasmids, Dr. Zheng-Li Shi (Wuhan Institute of Virology, CAS, Wuhan, China) for providing pVpack-GP and pVpack-VSV-G plasmids, Dr. Qun-Yuan Xu (Capital Medical University, Beijing, China) for providing the pLPCX plasmid, Prof. Tian-Xian Li (Wuhan Institute of Virology, CAS, Wuhan, China) for providing the marmoset B-lymphoblastoid (B95-8) and fetal rhesus monkey kidney (FRhk-4) cell lines. This work was supported by a grant of the Key Projects in the National Science & Technology Pillar Program during the Eleventh Five-Year Plan Period of China (2008ZX10001-002).

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  1. The State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Xiaohongshan 44, Wuhan, 430071, China

    Jian Gong, Xi-Hui Shen, Hui Qiu, Chao Chen & Rong-Ge Yang

  2. School of Life Science, Huzhou Teachers College, No.1 Xueshi Road., Huzhou, 313000, Zhejiang, China

    Jian Gong

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Correspondence to Rong-Ge Yang.

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Gong, J., Shen, XH., Qiu, H. et al. Rhesus monkey TRIM5α represses HIV-1 LTR promoter activity by negatively regulating TAK1/TAB1/TAB2/TAB3-complex-mediated NF-κB activation. Arch Virol 156, 1997–2006 (2011). https://doi.org/10.1007/s00705-011-1097-6

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