A Temporal Proteomic Map of Epstein-Barr Virus Lytic Replication in B Cells.

Cell Reports
Ina ErsingBenjamin E Gewurz

Abstract

Epstein-Barr virus (EBV) replication contributes to multiple human diseases, including infectious mononucleosis, nasopharyngeal carcinoma, B cell lymphomas, and oral hairy leukoplakia. We performed systematic quantitative analyses of temporal changes in host and EBV proteins during lytic replication to gain insights into virus-host interactions, using conditional Burkitt lymphoma models of type I and II EBV infection. We quantified profiles of >8,000 cellular and 69 EBV proteins, including >500 plasma membrane proteins, providing temporal views of the lytic B cell proteome and EBV virome. Our approach revealed EBV-induced remodeling of cell cycle, innate and adaptive immune pathways, including upregulation of the complement cascade and proteasomal degradation of the B cell receptor complex, conserved between EBV types I and II. Cross-comparison with proteomic analyses of human cytomegalovirus infection and of a Kaposi-sarcoma-associated herpesvirus immunoevasin identified host factors targeted by multiple herpesviruses. Our results provide an important resource for studies of EBV replication.

Citations

Feb 2, 2018·Viruses·Makda GebreBenjamin E Gewurz
Oct 26, 2018·Journal of Virology·Vladimir MajerciakZhi-Ming Zheng
Sep 4, 2019·Nature Reviews. Microbiology·Christian Münz
Nov 21, 2019·Proceedings of the National Academy of Sciences of the United States of America·Thejaswi NagarajuBill Sugden
Jun 11, 2020·Cancers·Diego GerminiYegor Vassetzky
Oct 23, 2019·Frontiers in Immunology·Korbinian BöslRichard K Kandasamy
Jun 18, 2020·Frontiers in Microbiology·Werner J D OuwendijkGeorges M G M Verjans
Apr 2, 2020·Seminars in Immunopathology·Alexander Buschle, Wolfgang Hammerschmidt
May 7, 2021·Journal of Virology·Melissa L WhyteAmy W Hudson
Jun 16, 2021·Annual Review of Virology·Alice Fletcher-Etherington, Michael P Weekes

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Methods Mentioned

BETA
flow cytometry
FACS
neddylation
ubiquitination
fluorescence-activated cell sorting

Software Mentioned

GSEA
DAVID
Excel
Plotter
Sequest

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