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

作者:Ersing Ina; Nobre Luis; Wang Liang Wei; Soday Lior; Ma Yijie; Paulo Joao A; Narita Yohei; Ashbaugh Camille W; Jiang Chang; Grayson Nicholas E; Kieff Elliott; Gygi Steven P; Weekes Michael P*; Gewurz Benjamin E*
来源:Cell Reports, 2017, 19(7): 1479-1493.
DOI:10.1016/j.celrep.2017.04.062

摘要

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-sarcomaassociated herpesvirus immunoevasin identified host factors targeted by multiple herpesviruses. Our results provide an important resource for studies of EBV replication.