Respiratory syncytial virus proteins modulate suppressors of cytokine signaling 1 and 3 and the type I interferon response to infection by a toll-like receptor pathway.
Respiratory syncytial virus (RSV) is a common cause of repeat infections throughout life and potentially severe lower respiratory tract illness in infants, young children, and the elderly. RSV proteins have been shown to contribute to immune evasion by several means, including modification of cytokine and chemokine responses whose expression is negatively regulated by suppressor of cytokine signaling (SOCS) proteins. In this study, we examine the role of SOCS1 and SOCS3 regulation of the type I interferon (IFN) response in normal fully-differentiated human bronchial epithelial cells infected with RSV or with an RSV mutant virus lacking the G gene. The results show that RSV G protein modulates SOCS expression to inhibit type I IFN and interferon-stimulated gene (ISG)-15 expression very early as well as late in infection, and that SOCS induction is linked to toll-like receptor (TLR) signaling by RSV F protein, as indicated by interferon-regulatory factor (IRF)-3 activation and nuclear translocation. These findings indicate that RSV surface proteins signal through the TLR pathway, suggesting that this may be an important mechanism to reduce type I IFN expression to aid virus replication.
Department of Infectious Diseases, College of Veterinary Medicine, Center for Disease Intervention, University of Georgia, Athens, Georgia.
Christine M
CM
Oshansky
Thomas M
TM
Krunkosky
Jamie
J
Barber
Les P
LP
Jones
Ralph A
RA
Tripp
D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000096:biosynthesis / Q000276:immunology; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D018113:Respiratory Syncytial Virus, Human / Q000502:physiology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*; D015533:Transcriptional Activation; D014452:Ubiquitins / Q000096:biosynthesis / Q000276:immunology; D014760:Viral Fusion Proteins / Q000502:physiology; D014779:Virus Replication
D016207:Cytokines; C526850:F protein, human respiratory syncytial virus; C502275:G glycoprotein, Respiratory syncytial virus; D050838:Interferon Regulatory Factor-3; D016898:Interferon-alpha; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051193:Toll-Like Receptors; D014452:Ubiquitins; D014760:Viral Fusion Proteins; C074034:ISG15 protein, human; D016899:Interferon-beta