Bat and pig Interferon-Induced Transmembrane Protein 3 restrict cell entry by influenza virus and lyssaviruses

Benfield, Camilla and Smith, Sarah E. and Wright, Edward and Wash, Rachael S. and Ferrara, Francesca and Temperton, Nigel J. and Kellam, Paul (2015) Bat and pig Interferon-Induced Transmembrane Protein 3 restrict cell entry by influenza virus and lyssaviruses. Journal of General Virology, 96 (5). ISSN 0022-1317. E-ISSN 1465-2099. (doi:https://doi.org/10.1099/vir.0.000058) (Full text available)

Abstract

Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor which blocks cytosolic entry of numerous viruses that utilise 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 the 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 bat orthologues. Ectopically-expressed pig and microbat IFITM3 co-localised with transferrin (early endosomes) and CD63 (late endosomes/multivesicular bodies) and trafficked from the plasma membrane into endosomes following live cell staining. Pig and microbat IFITM3 restricted cell entry mediated by multiple influenza HA subtypes and lyssavirus G proteins. Expression of pig or microbat IFITM3 in A549 cells reduced influenza virus yields and nucleoprotein expression. Conversely siRNA 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 sum, we show that IFITMs function as potent broad-spectrum antiviral effectors in two mammals - pigs and bats - identified as major reservoirs for emerging viruses.

Item Type:	Article
Subjects:	Q Science > QR Microbiology > QR355 Virology
Divisions:	Faculties > Sciences > Medway School of Pharmacy
Depositing User:	Nigel Temperton
Date Deposited:	16 Jan 2015 12:53 UTC
Last Modified:	17 Jan 2017 23:34 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/46718 (The current URI for this page, for reference purposes)