title: RSV replication is attenuated by counteracting expression of the suppressor of cytokine signaling (SOCS) molecules.
abstract: 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.
authors: Department of Microbiology, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan. don@fmu.ac.jp
authors: Koichi
authors: K
authors: Hashimoto
authors: Kei
authors: K
authors: Ishibashi
authors: Ken
authors: K
authors: Ishioka
authors: Dongchi
authors: D
authors: Zhao
authors: Masatoki
authors: M
authors: Sato
authors: Shinichiro
authors: S
authors: Ohara
authors: Yusaku
authors: Y
authors: Abe
authors: Yukihiko
authors: Y
authors: Kawasaki
authors: Yuka
authors: Y
authors: Sato
authors: Shin-Ichi
authors: S
authors: Yokota
authors: Nobuhiro
authors: N
authors: Fujii
authors: Ray Stokes
authors: RS
authors: Peebles
authors: Mitsuaki
authors: M
authors: Hosoya
authors: Tatsuo
authors: T
authors: Suzutani
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors*; D004847:Epithelial Cells / Q000821:virology; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques / Q000379:methods; D020868:Gene Silencing; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000502:physiology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis*; D015854:Up-Regulation; D014779:Virus Replication
chemical_list: D016207:Cytokines; D034741:RNA, Small Interfering; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human