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

Nicholas J Matheson; Jonathan Sumner; Kim Wals; Radu Rapiteanu; Michael P Weekes; Raphael Vigan; Julia Weinelt; Michael Schindler; Robin Antrobus; Ana S H Costa; Christian Frezza; Clary B Clish; Stuart J D Neil; Paul J Lehner

doi:10.1016/j.chom.2015.09.003

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

Nicholas J Matheson, Jonathan Sumner, Kim Wals, Radu Rapiteanu, Michael P Weekes, Raphael Vigan, Julia Weinelt, Michael Schindler, Robin Antrobus, Ana S H Costa, Christian Frezza, Clary B Clish, Stuart J D Neil, Paul J Lehner

Infectious Diseases

University of Cambridge
Department of Infectious Diseases, King's College London School of Medicine, Guy's Hospital, London SE1 9RT, UK.
Helmholtz Center Munich, Institute of Virology, 85764 Neuherberg, Germany; Institute of Medical Virology and Epidemiology of Viral Diseases, University Clinic Tübingen, 72076 Tübingen, Germany.
MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK.
Broad Institute of MIT and Harvard

Research output: Contribution to journal › Article › peer-review

137 Citations (Scopus)

123 Downloads (Pure)

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.

Original language	English
Pages (from-to)	409-23
Number of pages	15
Journal	Cell Host & Microbe
Volume	18
Issue number	4
Early online date	1 Oct 2015
DOIs	https://doi.org/10.1016/j.chom.2015.09.003
Publication status	Published - 14 Oct 2015

Keywords

Amino Acids/metabolism
CD4-Positive T-Lymphocytes/chemistry
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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cell Surface Proteomic Map_Acc10Sep2015Epub1Oct2015_GOLD VoR (CC BY)Final published version, 3.81 MBLicence: CC BY

Cite this

Matheson, N. J., Sumner, J., Wals, K., Rapiteanu, R., Weekes, M. P., Vigan, R., Weinelt, J., Schindler, M., Antrobus, R., Costa, A. S. H., Frezza, C., Clish, C. B., Neil, S. J. D., & Lehner, P. J. (2015). Cell Surface Proteomic Map of HIV Infection Reveals Antagonism of Amino Acid Metabolism by Vpu and Nef. Cell Host & Microbe, 18(4), 409-23. https://doi.org/10.1016/j.chom.2015.09.003

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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.",

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AU - Weekes, Michael P

AU - Vigan, Raphael

AU - Weinelt, Julia

AU - Schindler, Michael

AU - Antrobus, Robin

AU - Costa, Ana S H

AU - Frezza, Christian

AU - Clish, Clary B

AU - Neil, Stuart J D

AU - Lehner, Paul J

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AB - 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.

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KW - Host-Pathogen Interactions

KW - Human Immunodeficiency Virus Proteins/metabolism

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KW - Proteome/analysis

KW - Proteomics/methods

KW - Viral Regulatory and Accessory Proteins/metabolism

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JF - Cell Host & Microbe

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ER -

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

Abstract

Keywords

UN SDGs

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