Respiratory syncytial virus (RSV) attachment and nonstructural proteins modify the type I interferon response associated with suppressor of cytokine signaling (SOCS) proteins and IFN-stimulated gene-15 (ISG15).
Respiratory syncytial virus (RSV) is a major cause of severe lower airway disease in infants and young children, but no safe and effective RSV vaccine is yet available. Factors attributing to this problem are associated with an incomplete understanding of the mechanisms by which RSV modulates the host cell response to infection. In the present study, we investigate suppressor of cytokine signaling (SOCS)-1 and SOCS3 expression associated with the type I IFN and IFN-stimulated gene (ISG)-15 response following infection of mouse lung epithelial (MLE-15) cells with RSV or RSV mutant viruses lacking the G gene, or NS1 and NS2 gene deletions. Studies in MLE-15 cells are important as this cell line represents the distal bronchiolar and alveolar epithelium of mice, the most common animal model used to evaluate the host cell response to RSV infection, and exhibit morphologic characteristics of alveolar type II cells, a primary cell type targeted during RSV infection. These results show an important role for SOCS1 regulation of the antiviral host response to RSV infection, and demonstrate a novel role for RSV G protein manipulation of SOCS3 and modulation of ISG15 and IFNbeta mRNA expression.
Moore
Elizabeth C
EC
Department of Infectious Diseases, Center for Disease Intervention, University of Georgia, Athens, GA 30602, USA. ecmoore@uga.edu
Barber
Jamie
J
Tripp
Ralph A
RA
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000821:virology; D017353:Gene Deletion; D020869:Gene Expression Profiling; D007370:Interferon Type I / Q000276:immunology*; D051379:Mice; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000502:physiology; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis*; D014452:Ubiquitins / Q000096:biosynthesis*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology*; D053585:Virus Attachment
D016207:Cytokines; D007370:Interferon Type I; D050826:Suppressor of Cytokine Signaling Proteins; D014452:Ubiquitins; D017361:Viral Nonstructural Proteins; D015678:Viral Structural Proteins; C074034:ISG15 protein, human