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Roles of the ERK MAP Kinase in the Regulation of Proinflammatory and Apoptotic Responses in Chicken Macrophages Infected with H9N2 Avian Influenza Virus

University of California Davis

¹ E-mail: zxing{at}ucdavis.edu

The mitogen-activated protein kinase (MAPK) family are responsible for important signaling pathways, which regulate cell activation, differentiation, apoptosis, and immune responses. Studies have shown that influenza virus infection activates MAPK family members in mammals. While ERK1/2 is important for virus replication, activation of p38 controls the expression of RANTES, IL-8, and TNF-. In this study we report that avian influenza virus (AIV) activates ERK, p38 and JNK kinases in avian species. In chicken macrophages, while ERK was required for H9N2 AIV replication, ERK regulated proinflammatory cytokines IL-1b, IL-6 and IL-8, which is distinct from what has been previously reported in mammalian cells. Moreover, ERK alone suppressed TNF- and FasL and inhibited TNF family-mediated extrinsic apoptosis in H9N2-infected chicken macrophages. Taken together, these findings suggest that ERK signaling may uniquely play important roles in avian host responses to AIV infection.

Received 31 July 2009; accepted 27 October 2009.