Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A) Enhances IL-10 Production Through the Activation of Bruton's Tyrosine Kinase and STAT3

Overview

Journal Virology

Specialty Microbiology

Date 2016 Oct 30

PMID 27792904

Citations 27

Authors

Ryan Incrocci

Levi Barse

Amanda Stone

Sai Vagvala

Michael Montesano

Vijay Subramaniam

Michelle Swanson-Mungerson

Affiliations

Soon will be listed here.

Abstract

Previous data demonstrate that Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A) enhances IL-10 to promote the survival of LMP2A-expressing B cell lymphomas. Since STAT3 is an important regulator of IL-10 production, we hypothesized that LMP2A activates a signal transduction cascade that increases STAT3 phosphorylation to enhance IL-10. Using LMP2A-negative and -positive B cell lines, the data indicate that LMP2A requires the early signaling molecules of the Syk/RAS/PI3K pathway to increase IL-10. Additional studies indicate that the PI3K-regulated kinase, BTK, is responsible for phosphorylating STAT3, which ultimately mediates the LMP2A-dependent increase in IL-10. These data are the first to show that LMP2A signaling results in STAT3 phosphorylation in B cells through a PI3K/BTK-dependent pathway. With the use of BTK and STAT3 inhibitors to treat B cell lymphomas in clinical trials, these findings highlight the possibility of using new pharmaceutical approaches to treat EBV-associated lymphomas that express LMP2A.

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