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Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at early and late times after infection

Year: 2017
Type: article
Abstract: Latent Epstein-Barr virus (EBV) infection is causally linked to several human cancers. EBV expresses viral oncogenes that promote cell growth and inhibit the apoptotic response to uncontrolled proliferation. The EBV oncoprotein LMP1 constitutively activates NFκB and is critical for survival of EBV-immortalized B cells. However, during early infection EBV induces rapid B cell proliferation with low levels of LMP1 and little apoptosis. Therefore, we sought to define the mechanism of survival in the absence of LMP1/NFκB early after infection. We used BH3 profiling to query mitochondrial regulation of apoptosis and defined a transition from uninfected B cells (BCL-2) to early-infected (MCL-1/BCL-2) and immortalized cells (BFL-1). This dynamic change in B cell survival mechanisms is unique to virus-infected cells and relies on regulation of MCL-1 mitochondrial localization and BFL-1 transcription by the viral EBNA3A protein. This study defines a new role for EBNA3A in the suppression of apoptosis with implications for EBV lymphomagenesis.
Source: eLife
DOI: 10.7554/elife.22509
Authors: Alexander M Price, Joanne Dai, Quentin Bazot, Luv Patel, Pavel A Nikitin, Reza Djavadian, Peter S Winter, Cristina A Salinas, Ashley Perkins Barry, Kris C Wood, Eric C Johannsen, Anthony Letai, Martin J Allday, Micah A Luftig
Institutions: Duke University, Duke Medical Center, Imperial College London, Harvard University, Dana-Farber Cancer Institute, University of Wisconsin–Madison
Language: English
Subfield: Oncology
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,500
Funders: American Cancer Society, Wellcome Trust, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Dental and Craniofacial Research
Awards: G2504015987, Viral Oncology Training Grant, G440311441, Epigenetic reprogramming of B cells in viral persistence, disease pathogenesis and tumour immunosurveillance., G663672420, G6670064158, G7505140584, G790749344, G8916336546, Defining the Mechanisms of Epstein-Barr Virus Persistence and Recurrence, Center for AIDS Research
OpenAlex ID: W2606869403
FWCI: 2.694
Cites: 65
Cited by: 76
Related to: 10