title: Defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity.
abstract: The innate immune response to viruses is initiated when specialized cellular sensors recognize viral danger signals. Here we show that truncated forms of viral genomes that accumulate in infected cells potently trigger the sustained activation of the transcription factors IRF3 and NF-κB and the production type I IFNs through a mechanism independent of IFN signaling. We demonstrate that these defective viral genomes (DVGs) are generated naturally during respiratory infections in vivo even in mice lacking the type I IFN receptor, and their appearance coincides with the production of cytokines during infections with Sendai virus (SeV) or influenza virus. Remarkably, the hallmark antiviral cytokine IFNβ is only expressed in lung epithelial cells containing DVGs, while cells within the lung that contain standard viral genomes alone do not express this cytokine. Together, our data indicate that DVGs generated during viral replication are a primary source of danger signals for the initiation of the host immune response to infection.
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Karla
authors.initials: K
authors.lastname: Tapia
authors.forename: Won-Keun
authors.initials: WK
authors.lastname: Kim
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Xiomara
authors.initials: X
authors.lastname: Mercado-López
authors.forename: Emily
authors.initials: E
authors.lastname: Dunay
authors.forename: Megan
authors.initials: M
authors.lastname: Wise
authors.forename: Michael
authors.initials: M
authors.lastname: Adu
authors.forename: Carolina B
authors.initials: CB
authors.lastname: López
mesh_terms: D000818:Animals; D006224:Cricetinae; D004285:Dogs; D016679:Genome, Viral / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000276:immunology; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010253:Respirovirus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D029082:Sendai virus / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
chemical_list: D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D016328:NF-kappa B; D016899:Interferon-beta