Dual Functionality of HIV-1 Vif in APOBEC3 Counteraction and Cell Cycle Arrest

Daniel J. Salamango, Reuben S. Harris

Research output: Contribution to journalReview articlepeer-review

Abstract

Accessory proteins are a key feature that distinguishes primate immunodeficiency viruses such as human immunodeficiency virus type I (HIV-1) from other retroviruses. A prime example is the virion infectivity factor, Vif, which hijacks a cellular co-transcription factor (CBF-β) to recruit a ubiquitin ligase complex (CRL5) to bind and degrade antiviral APOBEC3 enzymes including APOBEC3D (A3D), APOBEC3F (A3F), APOBEC3G (A3G), and APOBEC3H (A3H). Although APOBEC3 antagonism is essential for viral pathogenesis, and a more than sufficient functional justification for Vif’s evolution, most viral proteins have evolved multiple functions. Indeed, Vif has long been known to trigger cell cycle arrest and recent studies have shed light on the underlying molecular mechanism. Vif accomplishes this function using the same CBF-β/CRL5 ubiquitin ligase complex to degrade a family of PPP2R5 phospho-regulatory proteins. These advances have helped usher in a new era of accessory protein research and fresh opportunities for drug development.

Original languageEnglish (US)
Article number622012
JournalFrontiers in Microbiology
Volume11
DOIs
StatePublished - Jan 12 2021

Bibliographical note

Funding Information:
This work was supported by NIAID R37-AI064046 (to RH). DS received salary support from an NIAID K99/R00 transition award (K99-AI147811). RH is the Margaret Harvey Schering Land Grant Chair for Cancer Research, a Distinguished University McKnight Professor, and an Investigator of the Howard Hughes Medical Institute.

Funding Information:
Funding. This work was supported by NIAID R37-AI064046 (to RH). DS received salary support from an NIAID K99/R00 transition award (K99-AI147811). RH is the Margaret Harvey Schering Land Grant Chair for Cancer Research, a Distinguished University McKnight Professor, and an Investigator of the Howard Hughes Medical Institute.

Publisher Copyright:
© Copyright © 2021 Salamango and Harris.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • APOBEC3
  • APOBEC3G
  • PPP2R5
  • Vif
  • cell cycle arrest

Fingerprint Dive into the research topics of 'Dual Functionality of HIV-1 Vif in APOBEC3 Counteraction and Cell Cycle Arrest'. Together they form a unique fingerprint.

Cite this