Open AccessShp‐2 contributes to anti‐ RSV activity in human pulmonary alveolar epithelial cells by interfering with the IFN ‐α‐induced Jak/Stat1 pathway
Author(s) -
Wang Saisai,
Zheng Gang,
Zhao Lifang,
Xu Feng,
Qian Jing
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12629
Subject(s) - stat1 , a549 cell , protein tyrosine phosphatase , biology , interferon , proto oncogene tyrosine protein kinase src , viral replication , phosphorylation , signal transduction , microbiology and biotechnology , virus , cell culture , virology , genetics
Src homology phosphotyrosyl phosphatase 2 (Shp‐2) is a ubiquitously expressed protein that is involved in a variety of cellular processes, including antiviral interferon signalling pathways. In this study, we investigated the role of Shp‐2 in the host cell interactions of human respiratory syncytial virus ( RSV ). We report significant changes in the expression of Shp‐2 in human pulmonary alveolar epithelial cells (A549) upon RSV infection. We also report that blocking Shp‐2 does not affect viral replication or virus‐induced interferon‐alpha ( IFN ‐α) production. Interestingly, whereas A549 cells were activated by IFN ‐α, the blocking of Shp‐2 resulted in increased viral replication that was associated with the reduced expression of the IFN ‐stimulated genes of 2′,5′‐oligoadenylate synthetases and Mx1, and the concomitant inhibition of Stat1 tyrosine phosphorylation. Our findings suggest that Shp‐2 contributes to the control of RSV replication and progeny production in pulmonary alveolar epithelial cells by interfering with IFN ‐α‐induced Jak/Stat1 pathway activation rather than by affecting the production of IFN ‐α itself.