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-βis mediated by induction of cell cycle arrest. Our recent data showed that RSV infection induced TGF-βin primary human epithelial cells and in mouse lungs. This novel induction of TGF-βby 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.

Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2011
Total Cost
$610,515
Indirect Cost
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State
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Zip Code
Minor, Radiah A Corn; Limmon, Gino V; Miller-DeGraff, Laura et al. (2010) Double-stranded RNA-activated protein kinase regulates early innate immune responses during respiratory syncytial virus infection. J Interferon Cytokine Res 30:263-72
Gibbs, John D; Ornoff, Douglas M; Igo, Heather A et al. (2009) Cell cycle arrest by transforming growth factor beta1 enhances replication of respiratory syncytial virus in lung epithelial cells. J Virol 83:12424-31
Cho, Hye-Youn; Imani, Farhad; Miller-DeGraff, Laura et al. (2009) Antiviral activity of Nrf2 in a murine model of respiratory syncytial virus disease. Am J Respir Crit Care Med 179:138-50
Li, Yin; Limmon, Gino V; Imani, Farhad et al. (2009) Induction of lactoferrin gene expression by innate immune stimuli in mouse mammary epithelial HC-11 cells. Biochimie 91:58-67