title: Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I.
abstract: 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.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Iris K
authors.initials: IK
authors.lastname: Pang
authors.forename: Padmini S
authors.initials: PS
authors.lastname: Pillai
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwasaki
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000821:virology; D016207:Cytokines / Q000032:analysis; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D005434:Flow Cytometry; D006652:Histological Techniques; D007113:Immunity, Innate / Q000276:immunology*; D007150:Immunohistochemistry; D009980:Influenza A virus / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000276:immunology / Q000821:virology*; D015398:Signal Transduction / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000378:metabolism*; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology
chemical_list: D016207:Cytokines; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
keywords: cytokine; inflammation; monocytes
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