Cell surface proteomic map of HIV infection reveals antagonism of amino acid metabolism by Vpu and Nef

ABSTRACT: Critical cell surface immunoreceptors downregulated by HIV 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. HIV downregulated >100 plasma membrane proteins, many without characterised roles in the immune system. An exclusive group of host factors were targeted by the viral accessory proteins Vpu or Nef, including the amino acid transporter SNAT1 and the serine carriers SERINC3/5. We focussed on SNAT1, a novel, ß- TrCP-dependent Vpu substrate. Antagonism of SNAT1 emerges in 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 novel paradigm of viral interference with immunometabolism.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Cell Culture

SUBMITTER: Yagnesh Umrania  

LAB HEAD: Paul Lehner

PROVIDER: PXD002934 | Pride | 2015-11-09

REPOSITORIES: Pride