title: Bat and pig IFN-induced transmembrane protein 3 restrict cell entry by influenza virus and lyssaviruses.
abstract: IFN-induced transmembrane protein 3 (IFITM3) is a restriction factor that blocks cytosolic entry of numerous viruses that utilize acidic endosomal entry pathways. In humans and mice, IFITM3 limits influenza-induced morbidity and mortality. Although many IFITM3-sensitive viruses are zoonotic, whether IFITMs function as antiviral restriction factors in mammalian species other than humans and mice is unknown. Here, IFITM3 orthologues in the microbat (Myotis myotis) and pig (Sus scrofa domesticus) were identified using rapid amplification of cDNA ends. Amino acid residues known to be important for IFITM3 function were conserved in the pig and microbat orthologues. Ectopically expressed pig and microbat IFITM3 co-localized with transferrin (early endosomes) and CD63 (late endosomes/multivesicular bodies). Pig and microbat IFITM3 restricted cell entry mediated by multiple influenza haemagglutinin subtypes and lyssavirus glycoproteins. Expression of pig or microbat IFITM3 in A549 cells reduced influenza virus yields and nucleoprotein expression. Conversely, small interfering RNA knockdown of IFITM3 in pig NPTr cells and primary microbat cells enhanced virus replication, demonstrating that these genes are functional in their species of origin at endogenous levels. In summary, we showed that IFITMs function as potent broad-spectrum antiviral effectors in two mammals - pigs and bats - identified as major reservoirs for emerging viruses.
authors.affiliation: Department of Pathology and Pathogen Biology, The Royal Veterinary College, Hatfield, UK.
authors.forename: Camilla T O
authors.initials: CTO
authors.lastname: Benfield
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Smith
authors.affiliation: Viral Pseudotype Unit (Fitzrovia), Faculty of Science and Technology, University of Westminster, London, UK.
authors.forename: Edward
authors.initials: E
authors.lastname: Wright
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: Rachael S
authors.initials: RS
authors.lastname: Wash
authors.affiliation: Viral Pseudotype Unit (Medway), School of Pharmacy, University of Kent, Chatham Maritime, Kent, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrara
authors.affiliation: Viral Pseudotype Unit (Medway), School of Pharmacy, University of Kent, Chatham Maritime, Kent, UK.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Temperton
authors.affiliation: MRC/UCL Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, UK.|Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Kellam
mesh_terms: D000818:Animals; D002685:Chiroptera; D017124:Conserved Sequence; D007372:Interferons / Q000276:immunology*; D018114:Lyssavirus / Q000276:immunology* / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009975:Orthomyxoviridae / Q000276:immunology* / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013552:Swine; D053586:Virus Internalization
chemical_list: D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D007372:Interferons