Hashimoto Koichi, Ishibashi Kei, Ishioka Ken, Zhao Dongchi, Sato Masatoki, Ohara Shinichiro, Abe Yusaku, Kawasaki Yukihiko, Sato Yuka, Yokota Shin-Ichi, Fujii Nobuhiro, Peebles Ray Stokes, Hosoya Mitsuaki, Suzutani Tatsuo
Department of Microbiology, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan.
Virology. 2009 Sep 1;391(2):162-70. doi: 10.1016/j.virol.2009.06.026. Epub 2009 Jul 12.
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 SOCS1, 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.
人呼吸道合胞病毒（Human RSV）每年都会在婴儿和老年人中引发呼吸道疾病的流行。呼吸道合胞病毒拮抗干扰素介导的抗病毒反应的机制包括抑制I型干扰素mRNA转录以及阻断JAK/STAT家族成员的信号转导。细胞因子信号转导抑制因子（SOCS）基因家族利用反馈回路来抑制细胞因子反应并阻断JAK/STAT信号通路的激活。为了评估SOCS分子颠覆对呼吸道合胞病毒感染的先天免疫反应的潜力，研究了八个SOCS家族基因。呼吸道合胞病毒感染上调了HEp-2细胞中SOCS1、SOCS3和CIS mRNA的表达。通过短干扰核糖核酸（siRNA）抑制SOCS1、SOCS3和CIS可抑制病毒复制。此外，抑制SOCS1、SOCS3或CIS可通过诱导STAT1/2磷酸化来激活I型干扰素信号。这些结果表明，呼吸道合胞病毒感染通过在上皮细胞中诱导SOCS1、SOCS3或CIS的表达来逃避先天抗病毒反应。
