Respiratory viral infections are associated with both the induction and exacerbation of allergic conditions including allergic asthma. These processes require activation of both innate and adaptive immune responses. The focus of our Lab is on the contribution of RSV- and dsRNA-responsive molecules in anti viral innate and adaptive immunity.? ? These molecules include the dsRNA-activated protein Kinase (PKR), scavenger receptor type-A (SR-A), and transforming growth factor-β (TGF-β). Our recent data showed that during viral infections and subsequent cell lysis, the released dsRNA was taken up into the cells through interaction with SR-A. After internalization, PKR, which is a dsRNA-specific signaling molecule, is activated and induces inflammatory and regulatory cytokines and chemokines. ? ? We previously reported that RSV replication was enhanced in the presence of TGF-β. Our recent data showed that enhancement of RSV replication by TGF-β is mediated by induction of cell cycle arrest. Our recent data showed that RSV infection induced TGF-β in primary human epithelial cells and in mouse lungs. This novel induction of TGF-β by RSV and its autocrine function on virus replication is under further investigation in our Lab.? ? During respiratory viral infections, for a balanced effector function, several types of immune responses are generated. These diverse and interrelated events include innate, Th1/Th2 and regulatory immune responses. But, the exact intracellular pathways that are differentially activated during viral infections leading to these responses are not yet completely understood. Our recent data using the PKR-/- mice showed that during RSV infection, PKR plays a critical role in the induction of innate and Th2 immune responses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES101784-05
Application #
7734538
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2008
Total Cost
$1,694,380
Indirect Cost
City
State
Country
United States
Zip Code
Limmon, Gino V; Arredouani, Mohamed; McCann, Kelly L et al. (2008) Scavenger receptor class-A is a novel cell surface receptor for double-stranded RNA. FASEB J 22:159-67
McCann, Kelly L; Imani, Farhad (2007) Transforming growth factor beta enhances respiratory syncytial virus replication and tumor necrosis factor alpha induction in human epithelial cells. J Virol 81:2880-6
Singh, Divyendu; McCann, Kelly L; Imani, Farhad (2007) MAPK and heat shock protein 27 activation are associated with respiratory syncytial virus induction of human bronchial epithelial monolayer disruption. Am J Physiol Lung Cell Mol Physiol 293:L436-45
Chiang, Eddie T; Persaud-Sawin, Dixie-Ann; Kulkarni, Sandhya et al. (2006) Bluetongue virus and double-stranded RNA increase human vascular permeability: role of p38 MAPK. J Clin Immunol 26:406-16
Stewart, Michael J; Kulkarni, Sandhya B; Meusel, Tiffany R et al. (2006) c-Jun N-terminal kinase negatively regulates dsRNA and RSV induction of tumor necrosis factor- alpha transcription in human epithelial cells. J Interferon Cytokine Res 26:521-33