Proteomic identification of nuclear processes manipulated by cytomegalovirus early during infection

Proteomics
Dominique M CarterScott S Terhune

Abstract

Human cytomegalovirus (HCMV) is a herpesvirus that is ubiquitously distributed worldwide and causes life-threating disease upon immunosuppression. HCMV expresses numerous proteins that function to establish an intracellular environment that supports viral replication. Like most DNA viruses, HCMV manipulates processes within the nucleus. We have quantified changes in the host cell nuclear proteome at 24 h post infection following infection with a clinical viral isolate. We have combined SILAC with multiple stages of fractionation to define changes. Tryptic peptides were analyzed by RP-HPLC combined with LC-MS/MS on an LTQ Orbitrap Velos mass spectrometer. Data from three biological replicates were processed with MaxQuant. A total of 1281 cellular proteins were quantified and 77 were found to be significantly differentially expressed. In addition, we observed 36 viral proteins associated with the nucleus. Diverse biological processes were significantly altered, including increased aspects of cell cycling, mRNA metabolism, and nucleocytoplasmic transport and decreased immune responses. We validated changes for several proteins including a subset of classical nuclear transport proteins. In addition, we demonstrated that disruption ...Continue Reading

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Citations

Mar 30, 2017·Molecular Systems Biology·Pierre M Jean BeltranIleana M Cristea
May 19, 2017·Nucleic Acids Research·Georgios EfstathiouIoannis Iliopoulos
May 14, 2020·Journal of the American Society for Mass Spectrometry·Michelle A KennedyIleana M Cristea
May 9, 2021·Nucleic Acids Research·Evangelos TheodorakisIoannis Iliopoulos
Jun 16, 2021·Annual Review of Virology·Alice Fletcher-Etherington, Michael P Weekes

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