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Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at early and late times after infection.
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.
Type
Journal articleSubject
B cellBH3 Profiling
Epstein-Barr virus
apoptosis
cancer biology
enhancer
human
infectious disease
microbiology
virus
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https://hdl.handle.net/10161/14611Published Version (Please cite this version)
10.7554/eLife.22509Publication Info
Price, Alexander M; Dai, Joanne; Bazot, Quentin; Patel, Luv; Nikitin, Pavel A; Djavadian,
Reza; ... Luftig, Micah A (2017). Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at early
and late times after infection. Elife, 6. 10.7554/eLife.22509. Retrieved from https://hdl.handle.net/10161/14611.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Micah Alan Luftig
Professor of Molecular Genetics and Microbiology
The Luftig laboratory studies viruses that cause cancer with an overarching goal of
defining the basic molecular mechanisms underlying pathogenesis and leveraging these
findings for diagnostic value and therapeutic intervention. Our work primarily focuses
on the common herpesvirus, Epstein-Barr virus (EBV). This virus latently infects virtually
all adults worldwide being acquired early in life. In the immune suppressed, EBV promotes
lymphomas in the B cells that it naturally infects. However, EB
Kris Cameron Wood
Associate Professor of Pharmacology and Cancer Biology
Our laboratory uses genomic and pharmacological approaches to understand how tumor
dependencies are shaped by cell intrinsic factors, environmental factors, and drug
treatments during the dynamic process of tumor evolution. To learn more, please visit
our laboratory website: https://woodlabduke.com/.
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