HIV-2/SIV Vpx targets a novel functional domain of STING to selectively inhibit cGAS–STING-mediated NF-κB signalling

Jiaming Su, Yajuan Rui, Meng Lou, Lu Yin, Hanchu Xiong, Zhenbang Zhou, Si Shen, Ting Chen, Zhengguo Zhang, Na Zhao, Wei Zhang, Yong Cai, Richard Markham, Shu Zheng, Rongzhen Xu, Wei Wei, Xiao Fang Yu

Research output: Contribution to journalArticle

Abstract

Innate immunity is the first line of host defence against pathogens. Suppression of innate immune responses is essential for the survival of all viruses. However, the interplay between innate immunity and HIV/SIV is only poorly characterized. We have discovered Vpx as a novel inhibitor of innate immune activation that associates with STING signalosomes and interferes with the nuclear translocation of NF-κB and the induction of innate immune genes. This new function of Vpx could be separated from its role in mediating degradation of the antiviral factor SAMHD1, and is conserved among diverse HIV-2/SIV Vpx. Vpx selectively suppressed cGAS–STING-mediated nuclear factor-κB signalling. Furthermore, Vpx and Vpr had complementary activities against cGAS–STING activity. Since SIVMAC lacking both Vpx and Vpr was less pathogenic than SIV deficient for Vpr or Vpx alone, suppression of innate immunity by HIV/SIV is probably a key pathogenic determinant, making it a promising target for intervention.

Original languageEnglish (US)
Pages (from-to)2552-2564
Number of pages13
JournalNature microbiology
Volume4
Issue number12
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology

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    Su, J., Rui, Y., Lou, M., Yin, L., Xiong, H., Zhou, Z., Shen, S., Chen, T., Zhang, Z., Zhao, N., Zhang, W., Cai, Y., Markham, R., Zheng, S., Xu, R., Wei, W., & Yu, X. F. (2019). HIV-2/SIV Vpx targets a novel functional domain of STING to selectively inhibit cGAS–STING-mediated NF-κB signalling. Nature microbiology, 4(12), 2552-2564. https://doi.org/10.1038/s41564-019-0585-4