Jembrana disease virus Vif antagonizes the inhibition of bovine APOBEC3 proteins through ubiquitin-mediate protein degradation

Virology. 2018 Jun:519:53-63. doi: 10.1016/j.virol.2018.03.028. Epub 2018 Apr 10.

Abstract

Viral infectivity factor (Vif) encoded by lentiviruses is essential for viral replication and escaping from antiviral activity of host defensive factors APOBEC3. Jembrana disease virus (JDV) causes an acute disease syndrome with approximately 20% case fatality rate in Bali cattle. However, the interplay mechanism between JDV Vif and Bos taurus APOBEC3 (btA3) is poorly understood. In this study, we determined that JDV Vif recruits ElonginB, ElonginC(ELOB/C), Cul2 and RBX1 but without the need of CBF-β to form E3 ubiquitin ligase and induces the degradation of btA3 proteins. Further investigation identified BC-box (T149LQ151) motif required for ELOB/C binding, Cul2 box (Y167xxxxV/X172) and a zinc-binding motif (H95-C113-H115-C133) required for Cul2 binding in JDV Vif. The precise mechanism of JDV Vif overcoming the antiviral activity of btA3 proteins is helpful for the application of the broad spectrum antiviral drug targeting conserved functional domains of various species Vif proteins in the future.

Keywords: APOBEC3; E3 ubiquitin ligase; Interplay mechanism; JDV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC Deaminases / metabolism*
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Cattle
  • Elongin / metabolism
  • Gene Products, vif / chemistry
  • Gene Products, vif / genetics
  • Gene Products, vif / metabolism*
  • HEK293 Cells
  • Humans
  • Lentiviruses, Bovine / genetics
  • Lentiviruses, Bovine / metabolism*
  • Protein Binding
  • Proteolysis*
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Elongin
  • Gene Products, vif
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • APOBEC Deaminases