HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation

Nature. 2015 Oct 8;526(7572):212-7. doi: 10.1038/nature15399. Epub 2015 Sep 30.


HIV-1 Nef, a protein important for the development of AIDS, has well-characterized effects on host membrane trafficking and receptor downregulation. By an unidentified mechanism, Nef increases the intrinsic infectivity of HIV-1 virions in a host-cell-dependent manner. Here we identify the host transmembrane protein SERINC5, and to a lesser extent SERINC3, as a potent inhibitor of HIV-1 particle infectivity that is counteracted by Nef. SERINC5 localizes to the plasma membrane, where it is efficiently incorporated into budding HIV-1 virions and impairs subsequent virion penetration of susceptible target cells. Nef redirects SERINC5 to a Rab7-positive endosomal compartment and thereby excludes it from HIV-1 particles. The ability to counteract SERINC5 was conserved in Nef encoded by diverse primate immunodeficiency viruses, as well as in the structurally unrelated glycosylated Gag from murine leukaemia virus. These examples of functional conservation and convergent evolution emphasize the fundamental importance of SERINC5 as a potent anti-retroviral factor.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Membrane / virology
  • Endosomes / chemistry
  • Endosomes / metabolism
  • Evolution, Molecular
  • Gene Products, gag / metabolism
  • Gene Products, nef / chemistry
  • Gene Products, nef / metabolism
  • HIV-1 / chemistry
  • HIV-1 / physiology*
  • Host Specificity
  • Host-Pathogen Interactions*
  • Humans
  • Leukemia Virus, Murine / chemistry
  • Leukemia Virus, Murine / physiology
  • Membrane Glycoproteins
  • Membrane Proteins / analysis
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / metabolism*
  • Neoplasm Proteins / metabolism
  • Primates / virology
  • Receptors, Cell Surface / metabolism
  • Virion / chemistry*
  • Virion / metabolism*
  • nef Gene Products, Human Immunodeficiency Virus / metabolism*
  • rab GTP-Binding Proteins / metabolism
  • rab7 GTP-Binding Proteins


  • Gene Products, gag
  • Gene Products, nef
  • Membrane Glycoproteins
  • Membrane Proteins
  • Neoplasm Proteins
  • Receptors, Cell Surface
  • SERINC3 protein, human
  • SERINC5 protein, human
  • nef Gene Products, Human Immunodeficiency Virus
  • rab7 GTP-Binding Proteins
  • rab7 GTP-binding proteins, human
  • rab GTP-Binding Proteins

Associated data

  • SRA/SRP062444