BACKGROUND: The interferon-induced transmembrane (IFITM) protein family comprises a class of restriction factors widely characterised in humans for their potent antiviral activity. Their biological activity is well documented in several animal species, but their genetic variation and biological mechanism is less well understood, particularly in avian species. RESULTS: Here we report the complete sequence of the domestic chicken Gallus gallus IFITM locus from a wide variety of chicken breeds to examine the detailed pattern of genetic variation of the locus on chromosome 5, including the flanking genes ATHL1 and B4GALNT4. We have generated chIFITM sequences from commercial breeds (supermarket-derived chicken breasts), indigenous chickens from Nigeria (Nsukka) and Ethiopia, European breeds and inbred chicken lines from the Pirbright Institute, totalling of 206 chickens. Through mapping of genetic variants to the latest chIFITM consensus sequence our data reveal that the chIFITM locus does not show structural variation in the locus across the populations analysed, despite spanning diverse breeds from different geographic locations. However, single nucleotide variants (SNVs) in functionally important regions of the proteins within certain groups of chickens were detected, in particular the European breeds and indigenous birds from Ethiopia and Nigeria. In addition, we also found that two out of four SNVs located in the chIFITM1 (Ser36 and Arg77) and chIFITM3 (Val103) proteins were simultaneously under positive selection. CONCLUSIONS: Together these data suggest that IFITM genetic variation may contribute to the capacities of different chicken populations to resist virus infection.

Addis Ababa University P O Box 32853 Addis Ababa Ethiopia

Amhara Regional Agricultural Research Institute P O Box 527 100 Bahir Dar Ethiopia

Center for Tropical Livestock Genetics and Health The Roslin Institute University of Edinburgh Easter Bush Midlothian EH25 9RG Scotland UK

Department of Medicine Division of Infectious Diseases Wright Fleming Wing St Mary's Campus Imperial College London Norfolk Place London W2 1PG UK

Department of Pharmaceutical Microbiology and Biotechnology Faculty of Pharmaceutical Sciences University of Nigeria Nsukka Enugu State 410001 Nigeria

Department of Zoology Faculty of Science Charles University Viničná 7 128 44 Prague Czech Republic

Imperial College London Department of Life Sciences South Kensington London SW7 2AZ UK

International Livestock Research Institute P O Box 5689 Addis Ababa Ethiopia

Kymab Ltd The Bennet Building Babraham Research Campus Cambridge CB22 3AT UK

School of Life Sciences University of Nottingham University Park Nottingham NG72RD UK

The Pirbright Institute Ash Road Woking GU24 0NF UK

Wellcome Sanger Institute Wellcome Genome Campus Hinxton Cambridge CB10 1SA UK

Zobrazit více v PubMed

Smith SE, et al. Chicken interferon-inducible transmembrane protein 3 restricts influenza viruses and lyssaviruses in vitro. J Virol. 2013;87(23):12957–12966. doi: 10.1128/JVI.01443-13. PubMed DOI PMC

Smith J, et al. A comparative analysis of host responses to avian influenza infection in ducks and chickens highlights a role for the interferon-induced transmembrane proteins in viral resistance. BMC Genomics. 2015;16:574. doi: 10.1186/s12864-015-1778-8. PubMed DOI PMC

Chesarino NM, McMichael TM, Yount JS. E3 ubiquitin ligase NEDD4 promotes influenza virus infection by decreasing levels of the antiviral protein IFITM3. PLoS Pathog. 2015;11(8):e1005095. doi: 10.1371/journal.ppat.1005095. PubMed DOI PMC

Everitt AR, et al. IFITM3 restricts the morbidity and mortality associated with influenza. Nature. 2012;484(7395):519–523. doi: 10.1038/nature10921. PubMed DOI PMC

Allen EK, et al. SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with risk of severe influenza in humans. Nat Med. 2017;23(8):975–983. doi: 10.1038/nm.4370. PubMed DOI PMC

Bassano I, et al. Accurate characterization of the IFITM locus using MiSeq and PacBio sequencing shows genetic variation in Galliformes. BMC Genomics. 2017;18(1):419. doi: 10.1186/s12864-017-3801-8. PubMed DOI PMC

2017. https://software.broadinstitute.org/gatk/. Accessed Aug 2018.

Agilent . SureSelectXT Target Enrichment System for Illumina Paired-End Multiplexed Sequencing Library. 2018.

Adeleke MA, Ozoje MO, Peters SO, Ikeobi CON, Adebambo AO, Olowofeso IO, Bamgbose AM, Adebambo OA. A preliminary screening of genetic lineage of Nigerian local chickens based on blood protein polymorphisms. Anim Genet Resourc. 2011;48:23–28. doi: 10.1017/S2078633610000962. DOI

Danecek P, et al. The variant call format and VCFtools. Bioinformatics. 2011;27(15):2156–2158. doi: 10.1093/bioinformatics/btr330. PubMed DOI PMC

NCBI . dbSNP Short Genetic variations. 2018.

NCBI . Gallus Gallus SNPdb. 2018.

Pronk S, et al. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics. 2013;29(7):845–854. doi: 10.1093/bioinformatics/btt055. PubMed DOI PMC

Murrell B, et al. FUBAR: a fast, unconstrained bayesian approximation for inferring selection. Mol Biol Evol. 2013;30(5):1196–1205. doi: 10.1093/molbev/mst030. PubMed DOI PMC

Murrell B, et al. Detecting individual sites subject to episodic diversifying selection. PLoS Genet. 2012;8(7):e1002764. doi: 10.1371/journal.pgen.1002764. PubMed DOI PMC

Delport W, et al. Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology. Bioinformatics. 2010;26(19):2455–2457. doi: 10.1093/bioinformatics/btq429. PubMed DOI PMC

Pond SL, Frost SD. Datamonkey: rapid detection of selective pressure on individual sites of codon alignments. Bioinformatics. 2005;21(10):2531–2533. doi: 10.1093/bioinformatics/bti320. PubMed DOI

Eswar N, et al. Comparative protein structure modeling using Modeller. Curr Protoc Bioinformatics. 2006;5:5–6. PubMed PMC

Jones DT. Protein secondary structure prediction based on position-specific scoring matrices. J Mol Biol. 1999;292(2):195–202. doi: 10.1006/jmbi.1999.3091. PubMed DOI

Ling S, et al. Combined approaches of EPR and NMR illustrate only one transmembrane helix in the human IFITM3. Sci Rep. 2016;6:24029. doi: 10.1038/srep24029. PubMed DOI PMC

Pietrucci F, Laio A. A collective variable for the efficient exploration of protein Beta-sheet structures: application to SH3 and GB1. J Chem Theory Comput. 2009;5(9):2197–2201. doi: 10.1021/ct900202f. PubMed DOI

Lindorff-Larsen K, et al. Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins. 2010;78(8):1950–8. PubMed PMC

William L, Jorgensen JC, Madura JD. Comparison of simple potential functions for simulating liquid water. J Chem Phys. 1983;79:926. doi: 10.1063/1.445869. DOI

Bussi G, Donadio D, Parrinello M. Canonical sampling through velocity rescaling. J Chem Phys. 2007;126(1):014101. doi: 10.1063/1.2408420. PubMed DOI

Chesarino NM, et al. Phosphorylation of the antiviral protein interferon-inducible transmembrane protein 3 (IFITM3) dually regulates its endocytosis and ubiquitination. J Biol Chem. 2014;289(17):11986–11992. doi: 10.1074/jbc.M114.557694. PubMed DOI PMC

John SP, et al. The CD225 domain of IFITM3 is required for both IFITM protein association and inhibition of influenza a virus and dengue virus replication. J Virol. 2013;87(14):7837–7852. doi: 10.1128/JVI.00481-13. PubMed DOI PMC

Muir WM, et al. Genome-wide assessment of worldwide chicken SNP genetic diversity indicates significant absence of rare alleles in commercial breeds. Proc Natl Acad Sci U S A. 2008;105(45):17312–17317. doi: 10.1073/pnas.0806569105. PubMed DOI PMC