RT Journal Article
SR Electronic
T1 Functional proteomic atlas of HIV-infection in primary human CD4+ T cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 389346
DO 10.1101/389346
A1 Adi Naamati
A1 James C Williamson
A1 Edward JD Greenwood
A1 Sara Marelli
A1 Paul J Lehner
A1 Nicholas J Matheson
YR 2018
UL http://biorxiv.org/content/early/2018/08/10/389346.abstract
AB Viruses manipulate host cells to enhance their replication, and the identification of host factors targeted by viruses has led to key insights in both viral pathogenesis and cellular physiology. We previously described global changes in cellular protein levels during human immunodeficiency virus (HIV) infection using transformed CEM-T4 T cells as a model. In this study, we develop an HIV reporter virus 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, including quantitation of >9,000 proteins across 4 different donors, and temporal profiling during T cell activation. Remarkably, amongst 650 cellular proteins significantly perturbed during HIV infection of primary T cells (q<0.05), almost 50% are regulated directly or indirectly by the viral accessory proteins Vpr, Vif, Nef and Vpu. The remainder have not been previously characterised, but include novel Vif-dependent targets FMR1 and DPH7, and 192 targets not identified and/or regulated in T cell lines, such as AIRD5A and PTPN22. We therefore provide a high-coverage functional proteomic atlas of HIV infection, and a mechanistic account of HIV-dependent changes in its natural target cell.