Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants
- University of Cambridge, United Kingdom
Abstract
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 >6,500 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 accessory protein Vif to be necessary and sufficient for CUL5-dependent proteasomal degradation of all members of the B56 family of regulatory subunits of the key cellular phosphatase PP2A (PPP2R5A-E). 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 PPP2R5 subunits is found in primate and non-primate lentiviral lineages, and remodeling of the cellular phosphoproteome is therefore a second ancient and conserved Vif function.
Data availability
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Temporal proteomic analysis of HIV-infection reveals remodelling of the cellular phosphoproteome by phylogenetically diverse lentiviral Vif variantsPublicly available at the EMBL PRIDE Archive (accession no: PXD004187).
Article and author information
Author details
Nicholas J Matheson
Funding
Wellcome Trust PRF (101835/Z/13/Z)
- Paul J Lehner
Wellcome Trust PRF (093964/Z/10/Z)
- Nicholas J Matheson
Addenbrooke's Charitable Trust, Cambridge University Hospitals
- Nicholas J Matheson
Raymond and Beverly Sackler Foundation
- Nicholas J Matheson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication
Copyright
© 2016, Greenwood et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants
eLife 5:e18296.
https://doi.org/10.7554/eLife.18296
