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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2013-08, Vol.110 (34), p.13910-13915
• Main Authors: Pang, Iris K., Pillai, Padmini S., Iwasaki, Akiko
• Format: Article
• Language: English
• Subjects: Animals; Antivirals; Biological Sciences; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - virology; Comparative analysis; Cytokines; Cytokines - analysis; DEAD Box Protein 58; DEAD-box RNA Helicases - metabolism; Dendritic cells; Dosage; Flow Cytometry; Histological Techniques; Immunity, Innate - immunology; Immunohistochemistry; Infections; inflammation; Influenza; Influenza A virus; Influenza A virus - immunology; innate immunity; Lungs; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred C57BL; Monocytes; Orthomyxoviridae; Orthomyxoviridae Infections - immunology; pathogens; Respiratory system; Respiratory Tract Infections - immunology; Respiratory Tract Infections - virology; retinoic acid; Rodents; Signal Transduction - immunology; Sublethal dosage; T cell receptors; Toll-like receptor 7; Toll-Like Receptor 7 - metabolism; Viral Load; virus replication; Virus Replication - physiology; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1303275110

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.