Epitopes described in "Hematopoietic-specific targeting of influenza A virus reveals replication requirements for induction of antiviral immune responses."

Article Authors:Ryan A Langlois; Andrew Varble; Mark A Chua; Adolfo GarcĂ­a-Sastre; Benjamin R tenOever
Article Title:Hematopoietic-specific targeting of influenza A virus reveals replication requirements for induction of antiviral immune responses.
Reference Detail
Reference ID:1026056
Abstract:A coordinated innate and adaptive immune response, orchestrated by antigen presenting cells (APCs), is required for effective clearance of influenza A virus (IAV). Although IAV primarily infects epithelial cells of the upper respiratory tract, APCs are also susceptible. To determine if virus transcription in these cells is required to generate protective innate and adaptive immune responses, we engineered IAV to be selectively attenuated in cells of hematopoietic origin. Incorporation of hematopoietic-specific miR-142 target sites into the nucleoprotein of IAV effectively silenced virus transcription in APCs, but had no significant impact in lung epithelial cells. Here we demonstrate that inhibiting IAV replication in APCs in vivo did not alter clearance, or the generation of IAV-specific CD8 T cells, suggesting that cross-presentation is sufficient for cytotoxic T lymphocyte activation. In contrast, loss of in vivo virus infection, selectively in APCs, resulted in a significant reduction of retinoic acid-inducible gene I-dependent type I IFN (IFN-I). These data implicate the formation of virus replication intermediates in APCs as the predominant trigger of IFN-I in vivo. Taking these data together, this research describes a unique platform to study the host response to IAV and provides insights into the mechanism of antigen presentation and the induction of IFN-I.
Affiliations:Department of Microbiology and Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
Reference Type:Literature
PubMed ID:22778433
Journal:Proc Natl Acad Sci U S A
Journal Volume:109
Article Pages:12117-22
Journal ISSN:0027-8424
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@1ab02686;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@22b1351a;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@20154fc1;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@5727185b;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@47b02b10
Article MeSH List:Adaptive Immunity(immunology); Animals; Antigen-Presenting Cells(virology); Base Sequence; Blotting, Northern; Blotting, Western; Cell Line; Cloning, Molecular; DNA Primers(genetics); Dogs; Fibroblasts; Flow Cytometry; Gene Expression Regulation, Viral(genetics; immunology); High-Throughput Nucleotide Sequencing; Humans; Immunity, Innate(immunology); Influenza A virus(immunology); Interferon Type I(metabolism); Macrophages; Mice; MicroRNAs(metabolism); Molecular Sequence Data; Nucleoproteins(genetics; metabolism); Virus Replication(immunology)
Curation Last Updated:2015-01-18 00:53:17