Dataset Information

Temporal proteomic analysis of HIV-Infection Reveals Remodelling of the Cellular Phosphoproteome by Phylogenetically Diverse Lentiviral Vif Variants

ABSTRACT: HIV accessory proteins manipulate host factors to evade cellular restriction and enhance viral replication. We used multiplex tandem mass tag (TMT)-based whole cell proteomics to gain a comprehensive, time-based overview of proteins and processes subverted during HIV infection. To make specific functional and mechanistic predictions and systematically identify candidate accessory protein targets, we categorized cellular proteins regulated by HIV according to their patterns of temporal expression. As well as depleting APOBEC family members, we found Vif to be necessary and sufficient for CUL5-dependent degradation of all members of the B56 family of regulatory subunits of the key cellular phosphatase PP2A. Quantitative phosphoproteomic analysis of HIV-infected cells confirmed Vif-dependent hyperphosphorylation of >200 cellular proteins, particularly substrates of the aurora kinases. The ability of Vif to target PP2A subunits spans primate and non-primate lentiviral lineages, and remodeling of the cellular phosphoproteome is therefore a second ancient and conserved Vif function.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Cell Culture

SUBMITTER: Yagnesh Umrania

LAB HEAD: Paul J Lehner

PROVIDER: PXD004187 | Pride | 2016-09-29

REPOSITORIES: Pride

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Publications

Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants.

Greenwood Edward Jd EJ Matheson Nicholas J NJ Wals Kim K van den Boomen Dick Jh DJ Antrobus Robin R Williamson James C JC Lehner Paul J PJ

eLife 20160930

Viruses manipulate host factors to enhance their replication and evade cellular restriction. We used multiplex tandem mass tag (TMT)-based whole cell proteomics to perform a comprehensive time course analysis of >6500 viral and cellular proteins during HIV infection. To enable specific functional predictions, we categorized cellular proteins regulated by HIV according to their patterns of temporal expression. We focussed on proteins depleted with similar kinetics to APOBEC3C, and found the viral ...[more]

PMID: 27690223

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Project description:We assessed correlates of protection from disease progression in a rare subset of HIV-infected individuals, viremic non-progressors (VNPs). These individuals have high viral load for several years, but in contrast to the majority of infected individuals, they do not progress to AIDS. Here we found this lack of progression was associated with selective preservation of two essential subsets of memory CD4+ T cells, central memory (TCM) and stem-cell memory (TSCM) cells. Compared to HIV-infected putative progressors, VNPs had higher proliferation of these indispensable subsets of memory cells, which was associated with the number of TCM. In addition, the long-lived CD4+ TCM and TSCM cells in VNPs had decreased HIV infection compared to the less critical effector memory CD4+ T cells, which indicates a possible mechanism by which VNPs maintain their CD4+ T cell pool after several years of infection, and remain free from AIDS progression. 6 HIV-infected patients fitting the clinical criteria of Viremic Non-Progressors were identified. VNPs were defined as having confirmed HIV-1 infection for at least 9 years with sustained plasma HIV RNA levels >10,000 copies/ml and maintenance of peripheral blood CD4+ T cell counts >500 cells/mm3 and a CD4% (of all lymphocytes) >15%. As controls, 7 HIV-infected Putative Progressors were identified. PPs were defined as having plasma HIV RNA levels >10,000 copies/mL, CD4+ T cell counts >400 cells/mm3 and having been initially infected with HIV 2-24 months prior to the index visit. The estimated date of initial HIV infection was calculated according to published algorithms that incorporate âde-tunedâ anti-HIV-1 antibody ELISA results or by a documented sero-conversion window of <6 months. All participants were required to be antiretroviral therapy (ART)-naÃ¯ve. RNA from 6 VNP and 7 PPs was purified from PAXgene whole blood tubes and hybridized to Affymetrix U133 Plus 2.0 arrays. During data analysis, one VNP patient (PID 4015) was determined to be an outlier and removed from further analysis. Thus, 5 VNPs and 7 PPs are represented in this Series.

Dataset Information

Temporal proteomic analysis of HIV-Infection Reveals Remodelling of the Cellular Phosphoproteome by Phylogenetically Diverse Lentiviral Vif Variants

Publications

Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants.

Similar Datasets

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