Double-stranded RNA-activated protein kinase regulates early innate immune responses during respiratory syncytial virus infection.
Respiratory syncytial virus (RSV) is the most common cause of childhood viral bronchiolitis and lung injury. Inflammatory responses significantly contribute to lung pathologies during RSV infections and bronchiolitis but the exact mechanisms have not been completely defined. The double-stranded RNA-activated protein kinase (PKR) functions to inhibit viral replication and participates in several signaling pathways associated with innate inflammatory immune responses. Using a functionally defective PKR (PKR(-/-)) mouse model, we investigated the role of this kinase in early events of RSV-induced inflammation. Our data showed that bronchoalveolar lavage (BAL) fluid from infected PKR(-/-) mice had significantly lower levels of several innate inflammatory cytokines and chemokines. Histological examinations revealed that there was less lung injury in infected PKR(-/-) mice as compared to the wild type. A genome-wide analysis showed that several early antiviral and immune regulatory genes were affected by PKR activation. These data suggest that PKR is a signaling molecule for immune responses during RSV infections.
Minor
Radiah A Corn
RA
North Carolina A&T University, Greensboro, North Carolina.
Limmon
Gino V
GV
Miller-DeGraff
Laura
L
Dixon
Darlene
D
Andrews
Danica M K
DM
Kaufman
Randal J
RJ
Imani
Farhad
F
D000818:Animals; D018925:Chemokines / Q000378:metabolism; D004789:Enzyme Activation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000201:enzymology / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000201:enzymology* / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000502:physiology; D015398:Signal Transduction; D019562:Viral Load / Q000276:immunology; D014779:Virus Replication; D019892:eIF-2 Kinase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D018925:Chemokines; D019892:eIF-2 Kinase; D020928:Mitogen-Activated Protein Kinases