Functional proteomic atlas of HIV infection in primary human CD4+ T cells

Author:

Naamati Adi1,Williamson James C12,Greenwood Edward JD12ORCID,Marelli Sara1,Lehner Paul J2ORCID,Matheson Nicholas J1ORCID

Affiliation:

1. Department of Medicine, University of Cambridge, Cambridge, United Kingdom

2. Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom

Abstract

Viruses manipulate host cells to enhance their replication, and the identification of cellular factors targeted by viruses has led to key insights into both viral pathogenesis and cell biology. In this study, we develop an HIV reporter virus (HIV-AFMACS) displaying a streptavidin-binding affinity tag at the surface of infected cells, allowing facile one-step selection with streptavidin-conjugated magnetic beads. We use this system to obtain pure populations of HIV-infected primary human CD4+ T cells for detailed proteomic analysis, and quantitate approximately 9000 proteins across multiple donors on a dynamic background of T cell activation. Amongst 650 HIV-dependent changes (q < 0.05), we describe novel Vif-dependent targets FMR1 and DPH7, and 192 proteins not identified and/or regulated in T cell lines, such as ARID5A and PTPN22. We therefore provide a high-coverage functional proteomic atlas of HIV infection, and a mechanistic account of host factors subverted by the virus in its natural target cell.

Funder

Medical Research Council

NHS Blood and Transplant

Wellcome

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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