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Selected Works of Erik Hill
Article
Signal Transducer and Activator of Transcription 3 Limits Epstein-Barr Virus Lytic Activation in B Lymphocytes
Journal of Virology (2013)
  • Erik Hill, Seton Hall University
  • Siva Koganti, State University of New York at Stony Brook
  • Jizu Zhi, State University of New York at Stony Brook
  • Cynthia Megyola, Yale University
  • Alexandra F. Freeman, National Institutes of Health
  • Umaimainthan Palendira, University of New South Wales
  • Stuart G. Tangye, University of New South Wales
  • Paul J. Farrell, Imperial College School of Medicine
  • Sumita Bhaduri-McIntosh, State University of New York at Stony Brook
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Abstract
Lytic activation of Epstein-Barr virus (EBV) is central to its life cycle and to most EBV-related diseases. However, not every EBV-infected B cell is susceptible to lytic activation. This lack of uniform susceptibility to lytic activation also directly impacts the success of viral oncolytic therapy for EBV cancers, yet determinants of susceptibility to lytic induction signals are not well understood. To determine if host factors influence susceptibility to EBV lytic activation, we developed a technique to separate lytic from refractory cells and reported that EBV lytic activation occurs preferentially in cells with lower levels of signal transducer and activator of transcription 3 (STAT3). Using this tool to detect single cells, we now extend the correlation between STAT3 and lytic versus refractory states to EBV-infected circulating B cells in patients with primary EBV infection, leading us to investigate whether STAT3 controls susceptibility to EBV lytic activation. In loss-of-function and gain-of-function studies in EBV-positive B lymphoma and lymphoblastoid cells, we found that the levels of functional STAT3 regulate susceptibility to EBV lytic activation. This prompted us to identify a pool of candidate cellular genes that might be regulated by STAT3 to limit EBV lytic activation. From this pool, we confirmed increases in transcript levels in refractory cells of a set of genes known to participate in transcription repression. Taken together, our findings place STAT3 at a critical crossroads between EBV latency and lytic activation, processes fundamental to EBV lymphomagenesis.
Disciplines
Publication Date
2013
DOI
10.1128/JVI.01762-13
Citation Information
Erik Hill, Siva Koganti, Jizu Zhi, Cynthia Megyola, et al.. "Signal Transducer and Activator of Transcription 3 Limits Epstein-Barr Virus Lytic Activation in B Lymphocytes" Journal of Virology Vol. 87 Iss. 21 (2013) p. 11438 - 11446 ISSN: 1098-5514
Available at: http://works.bepress.com/erik-hill/4/