Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants.
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 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.
Cambridge Institute for Medical Research, Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
Edward Jd
EJ
Greenwood
Cambridge Institute for Medical Research, Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
Nicholas J
0000-0002-3318-1851
NJ
Matheson
Cambridge Institute for Medical Research, Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
Kim
K
Wals
Cambridge Institute for Medical Research, Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
Dick Jh
DJ
van den Boomen
Cambridge Institute for Medical Research, Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
Robin
R
Antrobus
Cambridge Institute for Medical Research, Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
James C
JC
Williamson
Cambridge Institute for Medical Research, Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
Paul J
0000-0001-9383-1054
PJ
Lehner
D002478:Cells, Cultured; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000473:pathology*; D054884:Host-Pathogen Interactions; D006801:Humans; D010750:Phosphoproteins / Q000032:analysis*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D013997:Time Factors; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D010750:Phosphoproteins; D020543:Proteome; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1
HIV; PP2A; Vif; human; infectious disease; lentivirus; microbiology; phosphorylation; proteomics
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