Respiratory syncytial virus NS1 protein degrades STAT2 by inducing SOCS1 expression.
OBJECTIVE
Respiratory syncytial virus (RSV) nonstructural protein NS1 (NS1) has been shown to block interferon (IFN)-inducible antiviral signaling. The suppressor of cytokine signaling (SOCS) gene family could utilize a feedback loop to block the activation of the JAK/STAT signaling pathway, further inhibiting the activation of host type I IFN. We evaluated the role of the SOCS1 and SOCS3 genes in this antiviral mechanism.


METHODS
A humanized stable NS1 (rich in GC)-expressing plasmid was constructed, and A549 cells were transfected with it. Expression of the SOCS1, SOCS3, RIG-I, and TLR3 mRNAs was measured with real-time PCR. STAT2 and pSTAT2 expression was determined with Western blotting.


RESULTS
RSV NS1 upregulated SOCS1 mRNA expression 30-fold increase compared with the baseline level in very early phase (p < 0.01), and silence of RIG-I or TLR3 mRNA did not affect NS1-induced SOCS1 expression. NS1 inhibited IFN-α-induced STAT2 phosphorylation and degraded STAT2 in a time-dependent manner compared with the empty-vector control (p < 0.05).


CONCLUSIONS
RSV NS1 upregulates SOCS1 expression in a RIG-I- and TLR3-independent pathway, to inhibit STAT2 phosphorylation.
Department of Pediatrics, Zhongnan Hospital of Wuhan University, Wuhan, China.
Xiaodong
X
Xu
Junwen
J
Zheng
Kun
K
Zheng
Yan
Y
Hou
Feng
F
Zhao
Dongchi
D
Zhao
D015153:Blotting, Western; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D008969:Molecular Sequence Data; D010957:Plasmids; D059748:Proteolysis; D012367:RNA, Viral / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D050795:STAT2 Transcription Factor / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D014162:Transfection; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
D012367:RNA, Viral; C108944:SOCS1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D017361:Viral Nonstructural Proteins