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Signal transducer and activator of transcription 3 limits Epstein-Barr virus lytic activation in B lymphocytes.
J Virol. 2013 Nov; 87(21):11438-46.JV

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.

Authors+Show Affiliations

Division of Infectious Diseases, Department of Pediatrics and Stony Brook Children's Hospital, Stony Brook University, Stony Brook, New York, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

23966384

Citation

Hill, Erik R., et al. "Signal Transducer and Activator of Transcription 3 Limits Epstein-Barr Virus Lytic Activation in B Lymphocytes." Journal of Virology, vol. 87, no. 21, 2013, pp. 11438-46.
Hill ER, Koganti S, Zhi J, et al. Signal transducer and activator of transcription 3 limits Epstein-Barr virus lytic activation in B lymphocytes. J Virol. 2013;87(21):11438-46.
Hill, E. R., Koganti, S., Zhi, J., Megyola, C., Freeman, A. F., Palendira, U., Tangye, S. G., Farrell, P. J., & Bhaduri-McIntosh, S. (2013). Signal transducer and activator of transcription 3 limits Epstein-Barr virus lytic activation in B lymphocytes. Journal of Virology, 87(21), 11438-46. https://doi.org/10.1128/JVI.01762-13
Hill ER, et al. Signal Transducer and Activator of Transcription 3 Limits Epstein-Barr Virus Lytic Activation in B Lymphocytes. J Virol. 2013;87(21):11438-46. PubMed PMID: 23966384.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Signal transducer and activator of transcription 3 limits Epstein-Barr virus lytic activation in B lymphocytes. AU - Hill,Erik R, AU - Koganti,Siva, AU - Zhi,Jizu, AU - Megyola,Cynthia, AU - Freeman,Alexandra F, AU - Palendira,Umaimainthan, AU - Tangye,Stuart G, AU - Farrell,Paul J, AU - Bhaduri-McIntosh,Sumita, Y1 - 2013/08/21/ PY - 2013/8/23/entrez PY - 2013/8/24/pubmed PY - 2013/12/16/medline SP - 11438 EP - 46 JF - Journal of virology JO - J Virol VL - 87 IS - 21 N2 - 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. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/23966384/Signal_transducer_and_activator_of_transcription_3_limits_Epstein_Barr_virus_lytic_activation_in_B_lymphocytes_ L2 - https://journals.asm.org/doi/10.1128/JVI.01762-13?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -