RSV replication is attenuated by counteracting expression of the suppressor of cytokine signaling (SOCS) molecules.
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.
Hashimoto
Koichi
K
Department of Microbiology, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan. don@fmu.ac.jp
Ishibashi
Kei
K
Ishioka
Ken
K
Zhao
Dongchi
D
Sato
Masatoki
M
Ohara
Shinichiro
S
Abe
Yusaku
Y
Kawasaki
Yukihiko
Y
Sato
Yuka
Y
Yokota
Shin-Ichi
S
Fujii
Nobuhiro
N
Peebles
Ray Stokes
RS
Hosoya
Mitsuaki
M
Suzutani
Tatsuo
T
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
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