Cell Surface Proteomic Map of HIV Infection Reveals Antagonism of Amino Acid Metabolism by Vpu and Nef

Cell Host Microbe. 2015 Oct 14;18(4):409-23. doi: 10.1016/j.chom.2015.09.003. Epub 2015 Oct 1.


Critical cell surface immunoreceptors downregulated during HIV infection have previously been identified using non-systematic, candidate approaches. To gain a comprehensive, unbiased overview of how HIV infection remodels the T cell surface, we took a distinct, systems-level, quantitative proteomic approach. >100 plasma membrane proteins, many without characterized immune functions, were downregulated during HIV infection. Host factors targeted by the viral accessory proteins Vpu or Nef included the amino acid transporter SNAT1 and the serine carriers SERINC3/5. We focused on SNAT1, a β-TrCP-dependent Vpu substrate. SNAT1 antagonism was acquired by Vpu variants from the lineage of SIVcpz/HIV-1 viruses responsible for pandemic AIDS. We found marked SNAT1 induction in activated primary human CD4+ T cells, and used Consumption and Release (CoRe) metabolomics to identify alanine as an endogenous SNAT1 substrate required for T cell mitogenesis. Downregulation of SNAT1 therefore defines a unique paradigm of HIV interference with immunometabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • CD4-Positive T-Lymphocytes / chemistry*
  • CD4-Positive T-Lymphocytes / virology
  • Cell Membrane / chemistry*
  • HIV-1 / physiology*
  • Host-Pathogen Interactions*
  • Human Immunodeficiency Virus Proteins / metabolism*
  • Membrane Proteins / analysis*
  • Proteome / analysis
  • Proteomics / methods
  • Viral Regulatory and Accessory Proteins / metabolism*
  • nef Gene Products, Human Immunodeficiency Virus / metabolism*


  • Amino Acids
  • Human Immunodeficiency Virus Proteins
  • Membrane Proteins
  • Proteome
  • Viral Regulatory and Accessory Proteins
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1
  • vpu protein, Human immunodeficiency virus 1