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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Price, AM; Dai, J; Bazot, Q; Patel, L; Nikitin, PA; Djavadian, R; Winter, PS; Salinas, CA; Barry, AP; Wood, KC; Johannsen, EC; Letai, A; Allday, MJ; Luftig, MA

Published Date

  • April 20, 2017

Published In

Volume / Issue

  • 6 /

PubMed ID

  • 28425914

Pubmed Central ID

  • PMC5425254

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.22509


  • eng

Conference Location

  • England