The poly-proline tail of SIVmac Vpx provides gain of function for resistance to a cryptic proteasome-dependent degradation pathway
- School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin Province 130000 (China)
- Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, Jilin Province, China (China)
- Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, Jilin (China)
- Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medical Science, Jilin University, Changchun, Jilin 130021 (China)
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin (China)
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing (China)
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (United States)
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. - Highlights: • The poly-proline motif is essential for SIVmac Vpx resistance to a CRL4(DCAF1) E3 ligase-independent proteasome degradation. • The poly-proline tail confers the nuclear accumulation of Vpx. • The poly-proline tail enhances the ability of Vpx to promote viral infection of macrophages.
- OSTI ID:
- 22722971
- Journal Information:
- Virology, Vol. 511; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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