The poly-proline tail of SIVmac Vpx provides gain of function for resistance to a cryptic proteasome-dependent degradation pathway

Nannan Zhang, Haoran Guo, Jiaxin Yang, Guanchen Liu, Shuang Li, Siying Li, Dongyin Wang, Rui Li, Chang Shu, Hongmei Xu, Zhentong Wei, Honglan Huang, Songling Zhang, Pujun Gao, Shan Cen, Richard Bryan Markham, Yongsheng Wang, Xiao Fang Yu, Wei Wei

Research output: Contribution to journalArticle

Abstract

The lentiviral accessory protein Vpx is critical for viral infection of myeloid cells and acts by hijacking CRL4(DCAF1) E3 ubiquitin ligase to induce the degradation of the host restriction factor SAMHD1. It has been observed that the sequences from HIV-2 and SIVsmm/SIVmac Vpx contain a poly-proline tail which is distinct from other SIV Vpx proteins. However, the role of this region in Vpx function is controversial. Herein, we found proteasome-dependent degradation of a Vpx mutant lacking the poly-proline tail in the nucleus in a CRL4(DCAF1) E3 ligase-independent fashion. Unlike wild-type Vpx, the poly-proline tail mutant Vpx is partly defective in enhancing viral infection in macrophages. Our findings suggest that during Vpx evolution, Vpx of the HIV-2/SIVsm/SIVmac lineage is targeted by a CRL4(DCAF1) E3 ligase-independent ubiquitination pathway, and have gained this interesting region, allowing them to maintain nuclear accumulation as part of their adaptation to host cell regulation.

Original languageEnglish (US)
Pages (from-to)23-29
Number of pages7
JournalVirology
Volume511
DOIs
StatePublished - Nov 1 2017

Keywords

  • HIV/SIV
  • Poly-proline tail
  • Proteasome-dependent degradation
  • Vpx

ASJC Scopus subject areas

  • Virology

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  • Cite this

    Zhang, N., Guo, H., Yang, J., Liu, G., Li, S., Li, S., Wang, D., Li, R., Shu, C., Xu, H., Wei, Z., Huang, H., Zhang, S., Gao, P., Cen, S., Markham, R. B., Wang, Y., Yu, X. F., & Wei, W. (2017). The poly-proline tail of SIVmac Vpx provides gain of function for resistance to a cryptic proteasome-dependent degradation pathway. Virology, 511, 23-29. https://doi.org/10.1016/j.virol.2017.07.022