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

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Matheson, Nicholas J 
Sumner, Jonathan 
Wals, Kim 
Rapiteanu, Radu 
Weekes, Michael P 


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.



Amino Acids, CD4-Positive T-Lymphocytes, Cell Membrane, HIV-1, Host-Pathogen Interactions, Human Immunodeficiency Virus Proteins, Membrane Proteins, Proteome, Proteomics, Viral Regulatory and Accessory Proteins, nef Gene Products, Human Immunodeficiency Virus

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Cell Host Microbe

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Elsevier BV
Wellcome Trust (093964/Z/10/Z)
Wellcome Trust (093966/Z/10/Z)
Medical Research Council (MC_UU_12022/6)
Wellcome Trust (101835/Z/13/Z)
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (108070/Z/15/Z)
This work was supported by a Wellcome Trust PRF (WT101835) to PJL and SRF (WT098049) to SJDN, the NIHR Cambridge BRC, a Wellcome Trust Strategic Award to CIMR and the Addenbrooke’s Charitable Trust. MPW is a Wellcome Trust Fellow (093966/Z/10/Z) and NJM is a Wellcome Trust Training Fellow (093964/Z/10/Z) and Raymond and Beverly Sackler student.