Conserved interaction of lentiviral Vif molecules with HIV-1 Gag and differential effects of species-specific Vif on virus production

Wenwen Zheng, Limian Ling, Zhaolong Li, Hong Wang, Yajuan Rui, Wenying Gao, Shaohua Wang, Xing Su, Wei Wei, Xiao Fang Yu

Research output: Contribution to journalArticle

Abstract

The virion infectivity factor (Vif) open reading frame is conserved among most lentiviruses. Vif molecules contribute to viral replication by inactivating host antiviral factors, the APOBEC3 cytidine deaminases. However, various species of lentiviral Vif proteins have evolved different strategies for overcoming host APOBEC3. Whether different species of lentiviral Vif proteins still preserve certain common features has not been reported. Here, we show for the first time that diverse lentiviral Vif molecules maintain the ability to interact with the human immunodeficiency virus type 1 (HIV-1) Gag precursor (Pr55Gag) polyprotein. Surprisingly, bovine immunodeficiency virus (BIV) Vif, but not HIV-1 Vif, interfered with HIV-1 production and viral infectivity even in the absence of APOBEC3. Further analysis revealed that BIV Vif demonstrated an enhanced interaction with Pr55Gag compared to that of HIV-1 Vif, and BIV Vif defective for the Pr55Gag interaction lost its ability to inhibit HIV-1. The C-terminal region of capsid (CA) and the p2 region of Pr55Gag, which are important for virus assembly and maturation, were involved in the interaction. Transduction of CD4+ T cells with BIV Vif blocked HIV-1 replication. Thus, the conserved Vif- Pr55Gag interaction provides a potential target for the future development of antiviral strategies.

Original languageEnglish (US)
Article numbere00064-17
JournalJournal of Virology
Volume91
Issue number7
DOIs
StatePublished - 2017

Keywords

  • BIV Vif
  • HIV-1
  • HIV-1 Gag precursor
  • Viral infectivity factor

ASJC Scopus subject areas

  • Immunology
  • Virology

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    Zheng, W., Ling, L., Li, Z., Wang, H., Rui, Y., Gao, W., Wang, S., Su, X., Wei, W., & Yu, X. F. (2017). Conserved interaction of lentiviral Vif molecules with HIV-1 Gag and differential effects of species-specific Vif on virus production. Journal of Virology, 91(7), [e00064-17]. https://doi.org/10.1128/JVI.00064-17