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J Virol. 2015 Oct 14. pii: JVI.01593-15. [Epub ahead of print]
Duck IFITM3 mediates restriction of influenza viruses.
Blyth GA1, Chan WF1, Webster RG2, Magor KE3.
Author information
Abstract
Interferon Inducible Transmembrane Proteins (IFITMs) can restrict the entry of a wide range of viruses. IFITM3 localizes to endosomes and can potently restrict the replication of influenza A viruses (IAV), and several other viruses that also enter host cells through the endocytic pathway. Here we investigate whether IFITMs are involved in protection in ducks, the natural host of influenza. We identify and sequence duck IFITM1, IFITM2, IFITM3 and IFITM5. Using qPCR we demonstrate upregulation of these genes in lung tissue in response to highly pathogenic IAV infection 400-fold, 30-fold, 30-fold and 5-fold, respectively. We express each IFITM in chicken DF-1 cells and show duck IFITM1 localizes to the cell surface, while IFITM3 localizes to LAMP1 containing compartments. DF-1 cells stably expressing duck IFITM3 (but not IFITM1 or IFITM2) show increased restriction of replication of H1N1, H6N2 and H11N9 IAV strains, but not vesicular stomatitis virus. Although duck and human IFITM3 share only 38% identity, critical residues for viral restriction are conserved. We generate chimeric and mutant IFITM3 proteins and show duck IFITM3 does not require its N-terminal domain for endosomal localization or antiviral function, however, this N-terminal end confers endosomal localization and antiviral function on IFITM1. In contrast to mammalian IFITM3, the conserved YXXθ endocytosis signal sequence in the N-terminal domain of duck IFITM3 is not the sole contributor to correct endosomal localization. Despite significant structural and amino acid divergence, presumably due to host-viral co-evolution, duck IFITM3 is functional against IAV.
IMPORTANCE:
Immune IFITM genes are poorly conserved across species suggesting that selective pressure from host-specific viruses has driven this divergence. We wondered whether co-evolution between viruses and their natural host would result in evasion of IFITM restriction. Ducks are the natural host of avian influenza A viruses (IAV) and display little to no disease symptoms upon infection with most strains, including highly pathogenic avian influenza. We have characterized the duck IFITM locus, and identified IFITM3 as an important restrictor of several influenza A viruses, including avian strains. With only 38% amino acid identity to human IFITM3, duck IFITM3 possesses antiviral function against influenza. Thus, despite long co-evolution of virus and host effectors in the natural host, influenza evasion of IFITM3 restriction in ducks is not apparent.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26468537 [PubMed - as supplied by publisher]
Duck IFITM3 mediates restriction of influenza viruses.
Blyth GA1, Chan WF1, Webster RG2, Magor KE3.
Author information
Abstract
Interferon Inducible Transmembrane Proteins (IFITMs) can restrict the entry of a wide range of viruses. IFITM3 localizes to endosomes and can potently restrict the replication of influenza A viruses (IAV), and several other viruses that also enter host cells through the endocytic pathway. Here we investigate whether IFITMs are involved in protection in ducks, the natural host of influenza. We identify and sequence duck IFITM1, IFITM2, IFITM3 and IFITM5. Using qPCR we demonstrate upregulation of these genes in lung tissue in response to highly pathogenic IAV infection 400-fold, 30-fold, 30-fold and 5-fold, respectively. We express each IFITM in chicken DF-1 cells and show duck IFITM1 localizes to the cell surface, while IFITM3 localizes to LAMP1 containing compartments. DF-1 cells stably expressing duck IFITM3 (but not IFITM1 or IFITM2) show increased restriction of replication of H1N1, H6N2 and H11N9 IAV strains, but not vesicular stomatitis virus. Although duck and human IFITM3 share only 38% identity, critical residues for viral restriction are conserved. We generate chimeric and mutant IFITM3 proteins and show duck IFITM3 does not require its N-terminal domain for endosomal localization or antiviral function, however, this N-terminal end confers endosomal localization and antiviral function on IFITM1. In contrast to mammalian IFITM3, the conserved YXXθ endocytosis signal sequence in the N-terminal domain of duck IFITM3 is not the sole contributor to correct endosomal localization. Despite significant structural and amino acid divergence, presumably due to host-viral co-evolution, duck IFITM3 is functional against IAV.
IMPORTANCE:
Immune IFITM genes are poorly conserved across species suggesting that selective pressure from host-specific viruses has driven this divergence. We wondered whether co-evolution between viruses and their natural host would result in evasion of IFITM restriction. Ducks are the natural host of avian influenza A viruses (IAV) and display little to no disease symptoms upon infection with most strains, including highly pathogenic avian influenza. We have characterized the duck IFITM locus, and identified IFITM3 as an important restrictor of several influenza A viruses, including avian strains. With only 38% amino acid identity to human IFITM3, duck IFITM3 possesses antiviral function against influenza. Thus, despite long co-evolution of virus and host effectors in the natural host, influenza evasion of IFITM3 restriction in ducks is not apparent.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26468537 [PubMed - as supplied by publisher]