Structural insights for HIV-1 therapeutic strategies targeting Vif

Trends Biochem Sci. 2014 Sep;39(9):373-80. doi: 10.1016/j.tibs.2014.07.001. Epub 2014 Aug 12.

Abstract

HIV-1 viral infectivity factor (Vif) is a viral accessory protein that is required for HIV-1 infection due largely to its role in recruiting antiretroviral factors of the APOBEC3 (apolipoprotein B editing catalytic subunit-like 3) family to an E3 ubiquitin ligase complex for polyubiquitylation and proteasomal degradation. The crystal structure of the (near) full-length Vif protein in complex with Elongin (Elo)B/C, core-binding factor (CBF)β and Cullin (Cul)5 revealed that Vif has a novel structural fold. In our opinion the structural data revealed not only the protein-protein interaction sites that determine Vif stability and interaction with cellular proteins, but also motifs driving Vif homodimerization, which are essential in Vif functionality and HIV-1 infection. Vif-mediated protein-protein interactions are excellent targets for a new class of antiretroviral therapeutics to combat AIDS.

Keywords: APOBEC; Elongin B/C; core-binding factor β; cullin 5; viral infectivity factor.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • APOBEC-1 Deaminase
  • Antiviral Agents / therapeutic use
  • Cytidine Deaminase / metabolism
  • Drug Design*
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism
  • HIV Infections / virology
  • HIV-1 / metabolism*
  • Humans
  • vif Gene Products, Human Immunodeficiency Virus / chemistry*
  • vif Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • Antiviral Agents
  • vif Gene Products, Human Immunodeficiency Virus
  • APOBEC-1 Deaminase
  • APOBEC1 protein, human
  • Cytidine Deaminase