A New Class of Antiretroviral Enabling Innate Immunity by Protecting APOBEC3 From HIV Vif-Dependent Degradation

Trends Mol Med. 2018 May;24(5):507-520. doi: 10.1016/j.molmed.2018.03.004. Epub 2018 Mar 30.

Abstract

The infectivity of HIV depends on overcoming APOBEC3 (A3) innate immunity, predominantly through the expression of the viral protein Vif, which induces A3 degradation in the proteasome. Disruption of the functional interactions of Vif enables A3 mutagenesis of the HIV genome during viral replication, which can result in a broadly neutralizing antiviral effect. Vif function requires self-association along with interactions with A3 proteins, protein chaperones, and factors of the ubiquitination machinery and these are described here as a potential platform for novel antiviral drug discovery. This Review will examine the current state of development of Vif inhibitors that we believe to have therapeutic and functional cure potential.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Retroviral Agents / therapeutic use*
  • Cytidine Deaminase
  • Cytosine Deaminase / immunology*
  • Cytosine Deaminase / metabolism
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / immunology
  • HIV-1 / physiology
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunity, Innate / drug effects*
  • Protein Binding / drug effects
  • Proteolysis / drug effects
  • vif Gene Products, Human Immunodeficiency Virus / immunology*
  • vif Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • Anti-Retroviral Agents
  • vif Gene Products, Human Immunodeficiency Virus
  • vif protein, Human immunodeficiency virus 1
  • Cytosine Deaminase
  • APOBEC3 protein, human
  • Cytidine Deaminase