[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I

Iris K. Pang<SUP>1</SUP>, Padmini S. Pillai, and Akiko Iwasaki<SUP>2</SUP>
<ABBR>PNAS</ABBR> August 20, 2013 vol. 110 no. 34 13910-13915 - Published online before print August 5, 2013, doi: 10.1073/pnas.1303275110

Author Affiliations: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520

Edited* by Ruslan Medzhitov, Yale University School of Medicine, New Haven, CT, and approved July 16, 2013 (received for review February 19, 2013)


Induction of a proinflammatory response is the hallmark of host innate defense against invading pathogens. Host recognition of influenza A virus (IAV) infection relies on pattern-recognition receptors, including Toll-like receptor 7 (TLR7) and retinoic acid inducible gene-1 (RIG-I) for the activation of innate-immune responses. Here, we show that following a physiological low dose of IAV infection, viral sensing by either TLR7 or RIG-I induces a proinflammatory program that promotes viral replication. Transfer of bronchoalveolar lavage from infected wild-type mice into the airway of mice deficient in TLR7 and RIG-I pathways was sufficient to restore viral replication efficiency. Comparison of IAV-infected cells revealed that inflammatory mediators elicited by TLR7 and RIG-I signaling recruit viral target cells to the airway, thereby enhancing viral load within the respiratory tract. Our data suggest that IAV uses physiological levels of inflammatory responses for its replicative advantage and highlight the complex interplay between viruses and the host innate-immune responses.

inflammation ? cytokine ? monocytes


<SUP>1</SUP>Present address: Centre of Influenza Research, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.

<SUP>2</SUP>To whom correspondence should be addressed. E-mail: akiko.iwasaki@yale.edu.

Author contributions: I.K.P., P.S.P., and A.I. designed research; I.K.P. and P.S.P. performed research; I.K.P., P.S.P., and A.I. analyzed data; and I.K.P. and A.I. wrote the paper.

The authors declare no conflict of interest.

*This Direct Submission article had a prearranged editor.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1303275110/-/DCSupplemental.