RSV replication is attenuated by counteracting expression of the suppressor of cytokine signaling (SOCS) molecules

被引:48
作者
Hashimoto, Koichi [1 ,2 ]
Ishibashi, Kei [2 ,3 ]
Ishioka, Ken [2 ]
Zhao, Dongchi [2 ]
Sato, Masatoki [1 ]
Ohara, Shinichiro [1 ]
Abe, Yusaku [1 ]
Kawasaki, Yukihiko [1 ]
Sato, Yuka [2 ]
Yokota, Shin-ichi [4 ]
Fujii, Nobuhiro [4 ]
Peebles, Ray Stokes, Jr. [5 ]
Hosoya, Mitsuaki [1 ]
Suzutani, Tatsuo [2 ]
机构
[1] Fukushima Med Univ, Sch Med, Dept Pediat, Fukushima 9601295, Japan
[2] Fukushima Med Univ, Sch Med, Dept Microbiol, Fukushima 9601295, Japan
[3] Fukushima Med Univ, Sch Med, Dept Urol, Fukushima 9601295, Japan
[4] Sapporo Med Univ, Sch Med, Dept Microbiol, Sapporo, Hokkaido 0608556, Japan
[5] Vanderbilt Univ, Med Ctr, Ctr Lung Res, MCN T1217, Nashville, TN 37232 USA
基金
日本学术振兴会;
关键词
RSV; IFN; SOCS; siRNA; JAK/STAT; RESPIRATORY-SYNCYTIAL-VIRUS; NEGATIVE REGULATION; INTERFERON-ALPHA; EPITHELIAL-CELLS; INNATE IMMUNITY; PROTEINS; INHIBITION; INDUCTION; INFECTION; ALLERGY;
D O I
10.1016/j.virol.2009.06.026
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Human RSV causes an annual epidemic of respiratory tract illness in infants and in elderly. Mechanisms by which RSV antagonizes IFN-mediated antiviral responses include inhibition of type I IFN mRNA transcription and blocking signal transduction of JAK/STAT family members. The suppressor of cytokines signaling (SOCS) gene family utilizes a feedback loop to inhibit cytokine responses and block the activation of the JAK/STAT signaling pathway. To evaluate the potential of SOCS molecules to subvert the innate immune response to RSV infection, eight SOCS family genes were examined. RSV infection up-regulated SOCS1, SOCS3, and CIS mRNA expression in HEp-2 cells, Suppression of SOCS 1, SOCS3 and CIS by short interfering ribonucleic acid (siRNA) inhibited viral replication. Furthermore, inhibition of SOCS1, SOCS3, or CIS activated type I IFN signaling by inducing STAT1/2 phosphorylation. These results suggest that RSV infection escapes the innate antiviral response by inducing SOCS1, SOCS3 or CIS expression in epithelial cells. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:162 / 170
页数:9
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