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Selected Works of Erik Hill
Article
Cellular STAT3 Functions via PCBP2 To Restrain Epstein-Barr Virus Lytic Activation in B Lymphocytes
Journal of Virology (2015)
  • Siva Koganti, State University of New York at Stony Brook
  • Carissa Clark, State University of New York at Stony Brook
  • Jizu Zhi, State University of New York at Stony Brook
  • Xiaofan Li, State University of New York at Stony Brook
  • Emily I. Chen, State University of New York at Stony Brook
  • Sharmistha Chakrabortty, State University of New York at Stony Brook
  • Erik Hill, Seton Hall University
  • Sumita Bhaduri-McIntosh, State University of New York at Stony Brook
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Abstract
A major hurdle to killing Epstein-Barr virus (EBV)-infected tumor cells using oncolytic therapy is the presence of a substantial fraction of EBV-infected cells that does not support the lytic phase of EBV despite exposure to lytic cycle-promoting agents. To determine the mechanism(s) underlying this refractory state, we developed a strategy to separate lytic from refractory EBV-positive (EBV+) cells. By examining the cellular transcriptome in separated cells, we previously discovered that high levels of host STAT3 (signal transducer and activator of transcription 3) curtail the susceptibility of latently infected cells to lytic cycle activation signals. The goals of the present study were 2-fold: (i) to determine the mechanism of STAT3-mediated resistance to lytic activation and (ii) to exploit our findings to enhance susceptibility to lytic activation. We therefore analyzed our microarray data set, cellular proteomes of separated lytic and refractory cells, and a publically available STAT3 chromatin immunoprecipitation sequencing (ChIP-Seq) data set to identify cellular PCBP2 [poly(C)-binding protein 2], an RNA-binding protein, as a transcriptional target of STAT3 in refractory cells. Using Burkitt lymphoma cells and EBV+ cell lines from patients with hypomorphic STAT3 mutations, we demonstrate that single cells expressing high levels of PCBP2 are refractory to spontaneous and induced EBV lytic activation, STAT3 functions via cellular PCBP2 to regulate lytic susceptibility, and suppression of PCBP2 levels is sufficient to increase the number of EBV lytic cells. We expect that these findings and the genome-wide resources that they provide will accelerate our understanding of a longstanding mystery in EBV biology and guide efforts to improve oncolytic therapy for EBV-associated cancers.
Disciplines
Publication Date
2015
DOI
10.1128/JVI.00121-15
Citation Information
Siva Koganti, Carissa Clark, Jizu Zhi, Xiaofan Li, et al.. "Cellular STAT3 Functions via PCBP2 To Restrain Epstein-Barr Virus Lytic Activation in B Lymphocytes" Journal of Virology Vol. 89 Iss. 9 (2015) p. 5002 - 5011 ISSN: 1098-5514
Available at: http://works.bepress.com/erik-hill/5/