Multiple APOBEC3 restriction factors for HIV-1 and one Vif to rule them all

J Mol Biol. 2014 Mar 20;426(6):1220-45. doi: 10.1016/j.jmb.2013.10.033. Epub 2013 Nov 2.

Abstract

Several members of the APOBEC3 family of cellular restriction factors provide intrinsic immunity to the host against viral infection. Specifically, APOBEC3DE, APOBEC3F, APOBEC3G, and APOBEC3H haplotypes II, V, and VII provide protection against HIV-1Δvif through hypermutation of the viral genome, inhibition of reverse transcription, and inhibition of viral DNA integration into the host genome. HIV-1 counteracts APOBEC3 proteins by encoding the viral protein Vif, which contains distinct domains that specifically interact with these APOBEC3 proteins to ensure their proteasomal degradation, allowing virus replication to proceed. Here, we review our current understanding of APOBEC3 structure, editing and non-editing mechanisms of APOBEC3-mediated restriction, Vif-APOBEC3 interactions that trigger APOBEC3 degradation, and the contribution of APOBEC3 proteins to restriction and control of HIV-1 replication in infected patients.

Keywords: APOBEC3F; APOBEC3G; APOBEC3H; Vif; restriction factor.

Publication types

  • Review

MeSH terms

  • Cytidine Deaminase
  • Cytosine Deaminase / immunology*
  • DNA, Viral / genetics
  • HIV / physiology*
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV Infections / virology
  • Humans
  • Immunity, Innate / immunology*
  • Virus Replication / immunology*
  • vif Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • DNA, Viral
  • vif Gene Products, Human Immunodeficiency Virus
  • Cytosine Deaminase
  • APOBEC3 protein, human
  • Cytidine Deaminase