1. A Temporal Proteomic Map of Epstein-Barr Virus Lytic Replication in B Cells
- Author
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Ersing, I, Nobre, L, Wang, LW, Soday, L, Ma, Y, Paulo, JA, Narita, Y, Ashbaugh, CW, Jiang, C, Grayson, NE, Kieff, E, Gygi, SP, Weekes, MP, and Gewurz, BE
- Subjects
quantitative proteomics ,B cell receptor ,herpesvirus ,hemic and lymphatic diseases ,Epstein-Barr virus ,viral evasion ,complement ,tandem mass tag ,host-pathogen interaction ,lytic replication ,3. Good health ,immune evasion - 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.