Cell Reports (May 2017)

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

  • Ina Ersing,
  • Luis Nobre,
  • Liang Wei Wang,
  • Lior Soday,
  • Yijie Ma,
  • Joao A. Paulo,
  • Yohei Narita,
  • Camille W. Ashbaugh,
  • Chang Jiang,
  • Nicholas E. Grayson,
  • Elliott Kieff,
  • Steven P. Gygi,
  • Michael P. Weekes,
  • Benjamin E. Gewurz

DOI
https://doi.org/10.1016/j.celrep.2017.04.062
Journal volume & issue
Vol. 19, no. 7
pp. 1479 – 1493

Abstract

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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.

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