vir.0.000058.full.pdf (2.73 MB)
Bat and pig IFN-induced transmembrane protein 3 restrict cell entry by influenza virus and lyssaviruses
journal contribution
posted on 2023-06-09, 11:56 authored by Camilla T O Benfield, Sarah E Smith, Edward WrightEdward Wright, Rachael S Wash, Francesca Ferrara, Nigel J Temperton, Paul KellamIFN-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.
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Publication status
- Published
File Version
- Accepted version
Journal
Journal of General VirologyISSN
0022-1317Publisher
Microbiology SocietyExternal DOI
Issue
5Volume
96Page range
991-1005Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2018-02-07First Open Access (FOA) Date
2018-02-07First Compliant Deposit (FCD) Date
2018-02-06Usage metrics
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