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J. Virol. doi:10.1128/JVI.00989-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The RNA binding domain of the influenza A virus NS1 protein affects the secretion of TNF, IL-6 and IFN in primary murine tracheal epithelial cells

Depts. of Molecular Microbiology and Pathology & Immunology, Washington University in St. Louis School of Medicine, 660 S.Euclid Ave., Campus Box 8230, St. Louis, MO 63110

^* To whom correspondence should be addressed. Email: pekosz{at}borcim.wustl.edu.

	Abstract

Primary, differentiated respiratory epithelial cell cultures closely model the in vivo environment, and allow for studies of innate immune responses generated specifically by epithelial cells, the primary cell type infected by human influenza A virus strains. We used primary murine tracheal epithelial cell (mTEC) cultures to investigate antiviral and cytokine responses to influenza A virus infection, focusing on the contribution of the RNA binding domain of the NS1 protein. rWSN NS1 R38A replication is attenuated in mTEC cultures, however, viral antigen is detected predominantly in ciliated cells, similar to that of wild type virus. NS1 and NS1 R38A proteins display a primarily cytoplasmic localization in infected mTEC cultures. Increased production of TNF, IL-6, and IFN- is observed during rWSN NS1 R38A infection, and cytokines are secreted in a directional manner. Cytokine pretreatment of mTEC cultures and Vero cells suggest that rWSN NS1 R38A is more sensitive to the presence of antiviral/inflammatory cytokines than wild type virus. Our results demonstrate that the RNA binding domain is a critical regulator of both cytokine production and cytokine sensitivity during influenza A virus infection of primary tracheal epithelial cells.

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