Dataset Information

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

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, T-lymphocyte

DISEASE(S): Human Immunodeficiency Virus Infectious Disease

SUBMITTER: James Williamson

LAB HEAD: Nicholas J Matheson

PROVIDER: PXD012263 | Pride | 2019-03-08

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	PJL_AN-NM_PrimaryT_LNGFR-Ctrl.mzid.gz	Mzid
	PJL_AN-NM_PrimaryT_LNGFR-Ctrl_F.mzML	Mzml
	PJL_AN-NM_PrimaryT_LNGFR-Ctrl_F.pride.mgf.gz	Mgf
	PJL_AN-NM_PrimaryT_LNGFR-Ctrl_F1.raw	Raw
	PJL_AN-NM_PrimaryT_LNGFR-Ctrl_F10.raw	Raw

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

Naamati Adi A Williamson James C JC Greenwood Edward Jd EJ Marelli Sara S Lehner Paul J PJ Matheson Nicholas J NJ

eLife 20190312

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 c ...[more]

PMID: 30857592

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