Autocrine CCL3 and CCL4 induced by the oncoprotein LMP1 promote epstein-barr virus-triggered B cell proliferation

Shu Chun Tsai, Sue Jane Lin, Cheau Jye Lin, Ya-Ching Chou, Jiun Han Lin, Te Huei Yeh, Mei Ru Chen, Li Min Huang, Meng You Lu, Ya Chi Huang, Huan Yun Chen, Ching Hwa Tsai*

*Corresponding author for this work

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Epstein-Barr virus (EBV) alters the regulation and expression of a variety of cytokines in its host cells to modulate host immune surveillance and facilitate viral persistence. Using cytokine antibody arrays, we found that, in addition to the cytokines reported previously, two chemotactic cytokines, CCL3 and CCL4, were induced in EBV-infected B cells and were expressed at high levels in all EBV-immortalized lymphoblastoid cell lines (LCLs). Furthermore, EBV latent membrane protein 1 (LMP1)-mediated Jun N-terminal protein kinase activation was responsible for upregulation of CCL3 and CCL4. Inhibition of CCL3 and CCL4 in LCLs using a short hairpin RNA approach or by neutralizing antibodies suppressed cell proliferation and caused apoptosis, indicating that autocrine CCL3 and CCL4 are required for LCL survival and growth. Importantly, significant amounts of CCL3 were de-tected in EBV-positive plasma from immunocompromised patients, suggesting that EBV modulates this chemokine in vivo. This study reveals the regulatory mechanism and a novel function of CCL3 and CCL4 in EBV-infected B cells. CCL3 might be useful as a therapeutic target in EBV-associated lymphoproliferative diseases and malignancies.

Original languageEnglish
Pages (from-to)9041-9052
Number of pages12
JournalJournal of Virology
Volume87
Issue number16
DOIs
StatePublished - Aug 2013

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    Tsai, S. C., Lin, S. J., Lin, C. J., Chou, Y-C., Lin, J. H., Yeh, T. H., Chen, M. R., Huang, L. M., Lu, M. Y., Huang, Y. C., Chen, H. Y., & Tsai, C. H. (2013). Autocrine CCL3 and CCL4 induced by the oncoprotein LMP1 promote epstein-barr virus-triggered B cell proliferation. Journal of Virology, 87(16), 9041-9052. https://doi.org/10.1128/JVI.00541-13