Constitutive activation of interleukin-13/STAT6 contributes to Kaposi's sarcoma-associated herpesvirus-related primary effusion lymphoma cell proliferation and survival

Chong Wang, Caixia Zhu, Fang Wei, Liming Zhang, Xiaohui Mo, Yanling Feng, Jianqing Xu, Zhenghong Yuan, Erle Robertson, Qiliang Cai

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway has been associated with numerous human malignancies, including primary effusion lymphomas (PELs). PEL, a cancerous proliferation of B cells, is caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Previously we identified constitutive phosphorylation of STAT6 on tyrosine 641 (p-STAT6C) in PEL cell lines BC3 and BCBL1; however, the molecular mechanism leading to this activation remains unclear. Here we demonstrate that STAT6 activation tightly correlates with interleukin-13 (IL-13) secretion, JAK1/2 tyrosine phosphorylation, and reduced expression of SHP1 due to KSHV infection. Moreover, p-STAT6C and reduction of SHP1 were also observed in KS patient tissue. Notably, blockade of IL-13 by antibody neutralization dramatically inhibits PEL cell proliferation and survival. Taken together, these results suggest that IL-13/STAT6 signaling is modulated by KSHV to promote host cell proliferation and viral pathogenesis.

Original languageEnglish (US)
Pages (from-to)10416-10426
Number of pages11
JournalJournal of virology
Volume89
Issue number20
DOIs
StatePublished - 2015
Externally publishedYes

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