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

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

Author information

1
Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK. Electronic address: njm25@cam.ac.uk.
2
Department of Infectious Diseases, King's College London School of Medicine, Guy's Hospital, London SE1 9RT, UK.
3
Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
4
Helmholtz Center Munich, Institute of Virology, 85764 Neuherberg, Germany; Institute of Medical Virology and Epidemiology of Viral Diseases, University Clinic Tübingen, 72076 Tübingen, Germany.
5
MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK.
6
The Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
7
Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK. Electronic address: pjl30@cam.ac.uk.

Abstract

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.

PMID:
26439863
PMCID:
PMC4608997
DOI:
10.1016/j.chom.2015.09.003
[Indexed for MEDLINE]
Free PMC Article
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