{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T12:57:46Z","timestamp":1774097866906,"version":"3.50.1"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria","award":["RTA2015-00088-C03-03"],"award-info":[{"award-number":["RTA2015-00088-C03-03"]}]},{"name":"Agencia de Gesti\u00f3n de Ayudas Universitarias y de Investigaci\u00f3n (AGAUR).","award":["FI-DGR Pre-Doctoral Grant"],"award-info":[{"award-number":["FI-DGR Pre-Doctoral Grant"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Vet Res"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chickens are highly susceptible to highly pathogenic avian influenza viruses (HPAIVs). However, the severity of infection varies depending of the viral strain and the genetic background of the host. In this study, we evaluated the pathogenesis of two HPAIVs (H7N1 and H5N8) and assessed the susceptibility to the infection of local and commercial chicken breeds from Spain. Eight chicken breeds were intranasally inoculated with 10<jats:sup>5<\/jats:sup> ELD<jats:sub>50<\/jats:sub> of A\/Chicken\/Italy\/5093\/1999 (H7N1) or A\/Goose\/Spain\/IA17CR02699\/2017 (H5N8 clade 2.3.4.4. B) and monitored during 10\u00a0days. Chickens were highly susceptible to both HPAIVs, but H7N1 was considerably more virulent than H5N8 as demonstrated by the highest mortality rates and shortest mean death times (MDT). Both HPAIVs produced severe necrosis and intense viral replication in the central nervous system, heart and pancreas; however, the lesions and replication in other tissues were virus-dependent. High levels of viral RNA were detected by the oral route with both viruses. In contrast, a low number of H5N8-inoculated chickens shed by the cloacal route, demonstrating a different pattern of viral shedding dependent of the HPAIV. We found a high variation in the susceptibility to HPAIVs between the different chicken breeds. The birds carrying the genotype AA and AG at position 2032 in chicken Mx gene presented a slightly higher, but not significant, percentage of survival and a statistically significant longer MDT than GG individuals. Our study demonstrated that the severity of HPAI infection is largely dependent of the viral isolate and host factors, underlining the complexity of HPAI infections.<\/jats:p>","DOI":"10.1186\/s13567-020-00835-4","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T07:03:46Z","timestamp":1599721426000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Pathobiology of the highly pathogenic avian influenza viruses H7N1 and H5N8 in different chicken breeds and role of Mx 2032 G\/A polymorphism in infection outcome"],"prefix":"10.1186","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1987-5301","authenticated-orcid":false,"given":"Ra\u00fal","family":"S\u00e1nchez-Gonz\u00e1lez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Ramis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miquel","family":"Nofrar\u00edas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nabil","family":"Wali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Valle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00f3nica","family":"P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Perlas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nat\u00e0lia","family":"Maj\u00f3","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"835_CR1","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1637\/7763-110706-REGR.1","volume":"51","author":"DE Swayne","year":"2007","unstructured":"Swayne DE (2007) Understanding the complex pathobiology of high pathogenicity avian influenza viruses in birds. Avian Dis 51:242\u2013249","journal-title":"Avian Dis"},{"key":"835_CR2","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1080\/03079450802499118","volume":"37","author":"AR Spickler","year":"2008","unstructured":"Spickler AR, Trampel DW, Roth JA (2008) The onset of virus shedding and clinical signs in chickens infected with high-pathogenicity and low-pathogenicity avian influenza viruses. Avian Pathol 37:555\u2013577","journal-title":"Avian Pathol"},{"key":"835_CR3","doi-asserted-by":"crossref","first-page":"e0153649","DOI":"10.1371\/journal.pone.0153649","volume":"11","author":"A Matsuu","year":"2016","unstructured":"Matsuu A, Kobayashi T, Patchimasiri T, Shiina T, Suzuki S, Chaichoune K, Ratanakorn P, Hiromoto Y, Abe H, Parchariyanon S, Saito T (2016) Pathogenicity of genetically similar, H5N1 highly pathogenic avian influenza virus strains in chicken and the differences in sensitivity among different chicken breeds. PLoS One 11:e0153649","journal-title":"PLoS ONE"},{"key":"835_CR4","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.3201\/eid2412.171860","volume":"24","author":"P Alarcon","year":"2018","unstructured":"Alarcon P, Brouwer A, Venkatesh D, Duncan D, Dovas CI, Georgiades G, Monne I, Fusaro A, Dan A, \u015amietanka K, Ragias V, Breed AC, Chassalevris T, Goujgoulova G, Hjulsager CK, Ryan E, S\u00e1nchez A, Niqueux E, Tammiranta N, Zohari S, Stroud DA, Savi\u0107 V, Lewis NS, Brown IH (2018) Comparison of 2016\u201317 and previous epizootics of highly pathogenic Avian influenza H5 guangdong lineage in Europe. Emerg Infect Dis 24:2270\u20132283","journal-title":"Emerg Infect Dis"},{"key":"835_CR5","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1111\/tbed.12861","volume":"65","author":"S Napp","year":"2018","unstructured":"Napp S, Maj\u00f3 N, S\u00e1nchez-G\u00f3nzalez R, Vergara-Alert J (2018) Emergence and spread of highly pathogenic avian influenza A(H5N8) in Europe in 2016-2017. Transbound Emerg Dis 65:1217\u20131226","journal-title":"Transbound Emerg Dis"},{"key":"835_CR6","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.virol.2008.07.022","volume":"380","author":"L Sironi","year":"2008","unstructured":"Sironi L, Williams JL, Moreno-Martin AM, Ramelli P, Stella A, Jianlin H, Weigend S, Lombardi G, Cordioli P, Mariani P (2008) Susceptibility of different chicken lines to H7N1 highly pathogenic avian influenza virus and the role of Mx gene polymorphism coding amino acid position 631. Virology 380:152\u2013156","journal-title":"Virology"},{"key":"835_CR7","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1637\/11159-051615-RegR","volume":"60","author":"U Blohm","year":"2016","unstructured":"Blohm U, Weigend S, Preisinger R, Beer M, Hoffmann D (2016) Immunological competence of different domestic chicken breeds against avian influenza infection. Avian Dis 60:262\u2013268","journal-title":"Avian Dis"},{"key":"835_CR8","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1080\/03079457.2016.1142502","volume":"45","author":"D-H Lee","year":"2016","unstructured":"Lee D-H, Kwon J-H, Noh J-Y, Park J-K, Yuk S-S, Erdene-Ochir T-O, Lee J-B, Park S-Y, Choi I-S, Lee S-W, Song C-S (2016) Pathogenicity of the Korean H5N8 highly pathogenic avian influenza virus in commercial domestic poultry species. Avian Pathol 45:208\u2013211","journal-title":"Avian Pathol"},{"key":"835_CR9","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.4142\/jvs.2019.20.e27","volume":"20","author":"SC Park","year":"2019","unstructured":"Park SC, Song BM, Lee YN, Lee EK, Heo GB, Kye SJ, Lee KH, Bae YC, Lee YJ, Kim B (2019) Pathogenicity of clade 2.3.4.4 H5N6 highly pathogenic avian influenza virus in three chicken breeds from South Korea in 2016\/2017. J Vet Sci. 20:e27","journal-title":"J Vet Sci."},{"key":"835_CR10","first-page":"202","volume":"53","author":"S Suba","year":"2015","unstructured":"Suba S, Nagarajan S, Saxena VK, Kumar M, Vanamayya PR, Rajukumar K, Gowthaman V, Jain R, Singh DP, Dubey SC (2015) Pathology of a H5N1, highly pathogenic avian influenza virus, in two Indian native chicken breeds and a synthetic broiler line. Indian J Exp Biol 53:202\u2013207","journal-title":"Indian J Exp Biol"},{"key":"835_CR11","unstructured":"Minga UM, Msoffe PL, Gwakisa PS (2004) Biodiversity (variation) in disease resistance and in pathogens within rural chicken populations. In: International Health Network for Family Poultry (INFD). World Poultry Congress. 8-13 June 2004, Istanbul,Turkey. \u00a0"},{"key":"835_CR12","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1101\/gr.210702","volume":"12","author":"JH Ko","year":"2002","unstructured":"Ko JH, Jin HK, Asano A, Takada A, Ninomiya A, Kida H, Kokiyama H, Ohara M, Tzusuki M, Nishibori M, Mizutani M, Watanabe T (2002) Polymorphisms and the differential antiviral activity of the chicken Mx gene. Genome Res 12:595\u2013601","journal-title":"Genome Res"},{"key":"835_CR13","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1186\/1753-6561-5-S4-S25","volume":"5","author":"L Sironi","year":"2011","unstructured":"Sironi L, Williams JL, Stella A, Minozzi G, Moreno A, Ramelli P, Han J, Weigend S, Wan J, Lombardi G, Cordioli P, Mariani P (2011) Genomic study of the response of chicken to highly pathogenic avian influenza virus. BMC Proc 5:S25","journal-title":"BMC Proc"},{"key":"835_CR14","doi-asserted-by":"crossref","first-page":"7533","DOI":"10.1128\/JVI.00185-08","volume":"82","author":"CT Benfield","year":"2008","unstructured":"Benfield CT, Lyall JW, Kochs G, Tiley LS (2008) Asparagine 631 variants of the chicken Mx protein do not inhibit influenza virus replication in primary chicken embryo fibroblasts or in vitro surrogate assays. J Virol 82:7533\u20137539","journal-title":"J Virol"},{"key":"835_CR15","doi-asserted-by":"crossref","first-page":"8307","DOI":"10.1128\/JVI.00535-11","volume":"85","author":"B Schusser","year":"2011","unstructured":"Schusser B, Reuter A, von der Malsburg A, Penski N, Weigend S, Kaspers B, Staeheli P, H\u00e4rtle S (2011) Mx Is dispensable for interferon-mediated resistance of chicken cells against influenza a virus. J Virol 85:8307\u20138315","journal-title":"J Virol"},{"key":"835_CR16","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.3382\/ps.2012-02471","volume":"91","author":"Y Wang","year":"2012","unstructured":"Wang Y, Brahmakshatriya V, Lupiani B, Reddy S, Okimoto R, Li X, Chiang H, Zhou H (2012) Associations of chicken Mx1 polymorphism with antiviral responses in avian influenza virus infected embryos and broilers. Poult Sci 91:3019\u20133024","journal-title":"Poult Sci"},{"key":"835_CR17","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","volume":"27","author":"LJ Reed","year":"1938","unstructured":"Reed LJ, Muench H (1938) A simple method of estimating fifty per cent endpoints. Am J Epidemiol 27:493\u2013497","journal-title":"Am J Epidemiol"},{"key":"835_CR18","volume-title":"Les races aut\u00f2ctones catalanes (II)","author":"RuralCat","year":"2010","unstructured":"RuralCat (2010) Les races aut\u00f2ctones catalanes (II). Dossier t\u00e8cnic, Formaci\u00f3 i assessorament al sector agroalimentari"},{"key":"835_CR19","unstructured":"World Organization for Animal Health (OIE) (2010) Avian Influenza. Terrestrial Animal Health Code Chapter 10"},{"key":"835_CR20","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1080\/03079457.2011.551874","volume":"40","author":"AJ Chaves","year":"2011","unstructured":"Chaves AJ, Busquets N, Campos N, Ramis A, Dolz R, Rivas R, Valle R, Abad FX, Darji A, Maj\u00f3 N (2011) Pathogenesis of highly pathogenic avian influenza A virus (H7N1) infection in chickens inoculated with three different doses. Avian Pathol 40:163\u2013172","journal-title":"Avian Pathol"},{"key":"835_CR21","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1128\/JCM.40.9.3256-3260.2002","volume":"40","author":"E Spackman","year":"2002","unstructured":"Spackman E, Senne DA, Myers TJ, Bulaga LL, Garber LP, Perdue ML, Lohman P, Daum LT, Suarez DL (2002) Development of a real-time reverse transcriptase PCR assay for type A influenza virus and the avian H5 and H7 hemagglutinin subtypes. J Clin Microbiol 40:3256\u20133260","journal-title":"J Clin Microbiol"},{"key":"835_CR22","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.virusres.2009.12.005","volume":"149","author":"N Busquets","year":"2010","unstructured":"Busquets N, Alba A, Napp S, Sanchez A, Serrano E, Rivas R, N\u00fa\u00f1ez JI, Maj\u00f3 N (2010) Influenza A virus subtypes in wild birds in North-Eastern Spain (Catalonia). Virus Res 149:10\u201318","journal-title":"Virus Res"},{"key":"835_CR23","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.4238\/vol9-2gmr811","volume":"9","author":"L Sironi","year":"2010","unstructured":"Sironi L, Ramelli P, Williams JL, Mariani P (2010) PCR-RFLP genotyping protocol for chicken Mx gene G\/A polymorphism associated with the S631N mutation. Genet Mol Res 9:1104\u20131108","journal-title":"Genet Mol Res"},{"key":"835_CR24","volume-title":"Multiple comparisons. Handbook of Biological Satatistics","author":"JH McDonald","year":"2009","unstructured":"McDonald JH (2009) Multiple comparisons. Handbook of Biological Statistics, 2nd ed. Sparky House Publishing, Baltimore, Maryland. \u00a0","edition":"2n"},{"key":"835_CR25","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1297-9716-44-23","volume":"44","author":"K Bertran","year":"2013","unstructured":"Bertran K, Dolz R, Busquets N, Gamino V, Vergara-Alert J, Chaves AJ, Ramis A, Abad FX, H\u00f6fle U, Maj\u00f3 N (2013) Pathobiology and transmission of highly and low pathogenic avian influenza viruses in European quail (Coturnix c. coturnix). Vet Res 44:23","journal-title":"Vet Res"},{"key":"835_CR26","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1297-9716-42-24","volume":"42","author":"K Bertran","year":"2011","unstructured":"Bertran K, P\u00e9rez-Ram\u00edrez E, Busquets N, Dolz R, Ramis A, Darji A, Abad FX, Valle R, Chaves A, Vergara-Alert J, Barral M, H\u00f6fle U, Maj\u00f3 N (2011) Pathogenesis and transmissibility of highly (H7N1) and low (H7N9) pathogenic avian influenza virus infection in red-legged partridge (Alectoris rufa). Vet Res 42:24","journal-title":"Vet Res"},{"key":"835_CR27","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1007\/s00705-015-2428-9","volume":"160","author":"K Kanehira","year":"2015","unstructured":"Kanehira K, Uchida Y, Takemae N, Hikono H, Tsunekuni N, Saito T (2015) Characterization of an H5N8 influenza A virus isolated from chickens during an outbreak of severe avian influenza in Japan in April 2014. Arch Virol 160:1629\u20131643","journal-title":"Arch Virol"},{"key":"835_CR28","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.virol.2016.04.019","volume":"494","author":"K Bertran","year":"2016","unstructured":"Bertran K, Swayne DE, Pantin-jackwood MJ, Kapczynski DR, Spackman E, Suarez DL (2016) Lack of chicken adaptation of newly emergent Eurasian H5N8 and reassortant H5N2 high pathogenicity avian influenza viruses in the U.S. is consistent with restricted poultry outbreaks in the Pacific flyway during 2014\u20132015. Virology 494:190\u2013197","journal-title":"Virology"},{"key":"835_CR29","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.vetmic.2015.11.001","volume":"182","author":"H Sun","year":"2016","unstructured":"Sun H, Pu J, Hu J, Liu L, Xu G, Gao GF, Liu X, Liu J (2016) Characterization of clade 2.3.4.4 highly pathogenic H5 avian influenza viruses in ducks and chickens. Vet Microbiol 182:116\u2013122","journal-title":"Vet Microbiol"},{"key":"835_CR30","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1111\/tbed.12924","volume":"65","author":"E \u015awi\u0119to\u0144","year":"2018","unstructured":"\u015awi\u0119to\u0144 E, \u015amietanka K (2018) Phylogenetic and molecular analysis of highly pathogenic avian influenza H5N8 and H5N5 viruses detected in Poland in 2016-2017. Transbound Emerg Dis 65:1664\u20131670","journal-title":"Transbound Emerg Dis"},{"key":"835_CR31","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1126\/science.aaf8852","volume":"354","author":"The Global Consortium for H5N8 and Related Influenza Viruses","year":"2016","unstructured":"The Global Consortium for H5N8 and Related Influenza Viruses (2016) Role for migratory wild birds in the global spread of avian influenza H5N8. Science 354:213\u2013217","journal-title":"Science"},{"key":"835_CR32","doi-asserted-by":"crossref","first-page":"e68375","DOI":"10.1371\/journal.pone.0068375","volume":"8","author":"S Kuribayashi","year":"2013","unstructured":"Kuribayashi S, Sakoda Y, Kawasaki T, Tanaka T, Yamamoto N, Okamatsu M, Isoda N, Tsuda Y, Sunden Y, Umemura T, Nakajima N, Hasegawa H, Kida H (2013) Excessive cytokine response to rapid proliferation of highly pathogenic avian influenza viruses leads to fatal systemic capillary leakage in chickens. PLoS One 8:e68375","journal-title":"PLoS ONE"},{"key":"835_CR33","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s11262-019-01700-z","volume":"55","author":"A Suttie","year":"2019","unstructured":"Suttie A, Deng Y-M, Greenhill AR, Dussart P, Horwood PF, Karlsson EA (2019) Inventory of molecular markers affecting biological characteristics of avian influenza A viruses. Virus Genes 55:739\u2013768","journal-title":"Virus Genes"},{"key":"835_CR34","doi-asserted-by":"crossref","first-page":"11130","DOI":"10.1128\/JVI.01564-14","volume":"88","author":"Y Suzuki","year":"2014","unstructured":"Suzuki Y, Uchida Y, Tanikawa T, Maeda N, Takemae N, Saito T (2014) Amino acid substitutions in PB1 of Avian influenza viruses influence pathogenicity and transmissibility in chickens. J Virol 88:11130\u201311139","journal-title":"J Virol"},{"key":"835_CR35","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/s00705-009-0399-4","volume":"154","author":"J Wasilenko","year":"2009","unstructured":"Wasilenko J, Sarmento L, Pantin-jackwood MJ (2009) A single substitution in amino acid 184 of the NP protein alters the replication and pathogenicity of H5N1 avian influenza viruses in chickens. Arch Virol 154:969\u2013979","journal-title":"Arch Virol"},{"key":"835_CR36","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1080\/03079450020016779","volume":"29","author":"I Capua","year":"2000","unstructured":"Capua I, Mutinelli F, Marangon S, Alexander DJ (2000) H7N1 avian influenza in Italy (1999 to 2000) in intensively reared chickens and turkeys. Avian Pathol 29:537\u2013543","journal-title":"Avian Pathol"},{"key":"835_CR37","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1007\/s00705-013-1762-z","volume":"158","author":"J Maruyama","year":"2013","unstructured":"Maruyama J, Okamatsu M, Soda K, Sakoda Y, Kida H (2013) Factors responsible for pathogenicity in chickens of a low-pathogenic H7N7 avian influenza virus isolated from a feral duck. Arch Virol 158:2473\u20132478","journal-title":"Arch Virol"},{"key":"835_CR38","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1099\/jgv.0.000674","volume":"98","author":"EM Elgendy","year":"2017","unstructured":"Elgendy EM, Arai Y, Kawashita N, Daidoji T, Takagi T, Ibrahim MS, Nakaya T, Watanabe Y (2017) Identification of polymerase gene mutations that affect viral replication in H5N1 influenza viruses isolated from pigeons. J Gen Virol 98:6\u201317","journal-title":"J Gen Virol"},{"key":"835_CR39","doi-asserted-by":"crossref","first-page":"9568","DOI":"10.1128\/JVI.00943-14","volume":"88","author":"L Zhong","year":"2014","unstructured":"Zhong L, Wang X, Li Q, Liu D, Chen H, Zhao M, Gu X, He L, Liu X, Gu M, Peng D, Liu X (2014) Molecular mechanism of the airborne transmissibility of H9N2 avian influenza A viruses in chickens. J Virol 88:9568\u20139578","journal-title":"J Virol"},{"key":"835_CR40","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1128\/JVI.01648-10","volume":"85","author":"T Tada","year":"2011","unstructured":"Tada T, Suzuki K, Sakurai Y, Kubo M, Okada H, Itoh T, Tsukamoto K (2011) NP body domain and PB2 contribute to increased virulence of H5N1 highly pathogenic avian influenza viruses in chickens. J Virol 85:1834\u20131846","journal-title":"J Virol"},{"key":"835_CR41","doi-asserted-by":"crossref","first-page":"e0137989","DOI":"10.1371\/journal.pone.0137989","volume":"10","author":"N Nao","year":"2015","unstructured":"Nao N, Kajihara M, Manzoor R, Maruyama J, Yoshida R, Muramatsu M, Miyamoto H, Igarashi M, Eguchi N, Sato M, Kondoh T, Okamatsu M, Sakoda Y, Kida H, Takada A (2015) A single amino acid in the m1 protein responsible for the different pathogenic potentials of H5N1 highly pathogenic avian influenza virus strains. PLoS One 10:e0137989","journal-title":"PLoS ONE"},{"key":"835_CR42","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.3389\/fmicb.2018.02546","volume":"9","author":"L Rodriguez","year":"2018","unstructured":"Rodriguez L, Nogales A, Iqbal M, Perez DR, Mart\u00ednez-Sobrido L (2018) Identification of amino acid residues responsible for inhibition of host gene expression by influenza a H9N2 NS1 targeting of CPSF30. Front Microbiol 9:2546","journal-title":"Front Microbiol"},{"key":"835_CR43","doi-asserted-by":"crossref","first-page":"11115","DOI":"10.1128\/JVI.00993-06","volume":"80","author":"Z Li","year":"2006","unstructured":"Li Z, Jiang Y, Jiao P, Wang A, Zhao F, Tian G, Wang X, Yu K, Bu Z, Chen H (2006) The NS1 gene contributes to the virulence of H5N1 avian influenza viruses. J Virol 80:11115\u201311123","journal-title":"J Virol"},{"key":"835_CR44","doi-asserted-by":"crossref","first-page":"13493","DOI":"10.1038\/srep13493","volume":"5","author":"O Stech","year":"2015","unstructured":"Stech O, Veits J, Abdelwhab E-SM, Wessels U, Mettenleiter TC, Stech J (2015) The neuraminidase stalk deletion serves as major virulence determinant of H5N1 highly pathogenic avian influenza viruses in chicken. Sci Rep 5:13493","journal-title":"Sci Rep"},{"key":"835_CR45","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.3382\/ps\/pew028","volume":"95","author":"E-K Lee","year":"2016","unstructured":"Lee E-K, Song B-M, Kang H-M, Woo S-H, Heo G-B, Jung SC, Park YH, Lee Y-J, Kim J-H (2016) Experimental infection of SPF and Korean native chickens with highly pathogenic avian influenza virus (H5N8). Poult Sci 95:1015\u20131019","journal-title":"Poult Sci"},{"key":"835_CR46","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1637\/8888-042409-ResNote.1","volume":"54","author":"HD Hunt","year":"2010","unstructured":"Hunt HD, Jadhao S, Swayne DE (2010) Major histocompatibility complex and background genes in chickens influence susceptibility to high pathogenicity avian influenza virus. Avian Dis 54:572\u2013575","journal-title":"Avian Dis"},{"key":"835_CR47","doi-asserted-by":"crossref","first-page":"551","DOI":"10.3201\/eid2503.181040","volume":"25","author":"M Souvestre","year":"2019","unstructured":"Souvestre M, Guinat C, Niqueux E, Robertet L, Croville G, Paul M, Schmitz A, Bronner A, Eterradossi N, Gu\u00e9rin JL (2019) Role of backyard flocks in transmission dynamics of highly pathogenic avian influenza A(H5N8) Clade 2.3.4.4, France, 2016\u20132017. Emerg Inf Dis 25:551\u2013554","journal-title":"Emerg Inf Dis"},{"key":"835_CR48","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/j.1365-2052.2004.01096.x","volume":"35","author":"JH Ko","year":"2004","unstructured":"Ko JH, Takada A, Mitsuhashi T, Agui T, Watanabe T (2004) Native antiviral specificity of chicken Mx protein depends on amino acid variation at position 631. Anim Genet 35:119\u2013122","journal-title":"Anim Genet"},{"key":"835_CR49","doi-asserted-by":"crossref","first-page":"120","DOI":"10.2141\/jpsa.43.120","volume":"43","author":"K Boonyanuwat","year":"2006","unstructured":"Boonyanuwat K, Thummabutra S, Sookmanee N, Vatchavalkhu V, Siripholvat V, Mitsuhashi T (2006) Influence of MHC class II haplotypes on avian influenza traits in Thai indigenous chicken. J Poult Sci 43:120\u2013125","journal-title":"J Poult Sci"},{"key":"835_CR50","doi-asserted-by":"crossref","first-page":"13445","DOI":"10.1128\/JVI.01682-12","volume":"86","author":"J Verhelst","year":"2012","unstructured":"Verhelst J, Parthoens E, Schepens B, Fiers W, Saelens X (2012) Interferon-Inducible protein Mx1 inhibits influenza virus by interfering with functional viral ribonucleoprotein complex. J Virol 86:13445\u201313455","journal-title":"J Virol"},{"key":"835_CR51","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s10528-006-9040-3","volume":"44","author":"T Seyama","year":"2006","unstructured":"Seyama T, Ko JH, Ohe M, Sasaoka N, Okada A, Gomi H, Yoneada A, Ueda J, Nishibori M, Okamoto S, Maeda Y, Watanabe T (2006) Population research of genetic polymorphism at amino acid position 631 in chicken Mx protein with differential antiviral activity. Biochem Genet 44:437\u2013448","journal-title":"Biochem Genet"},{"key":"835_CR52","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.3382\/ps.2010-00826","volume":"89","author":"CG Yin","year":"2010","unstructured":"Yin CG, Zhang CS, Zhang AM, Qin HW, Wang LX, Du LX, Zhao GP (2010) Expression analyses and antiviral properties of the Beijing-You and White Leghorn myxovirus resistance gene with different amino acids at position 631. Poult Sci 89:2259\u20132264","journal-title":"Poult Sci"},{"key":"835_CR53","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s00251-007-0235-5","volume":"59","author":"D Balkissoon","year":"2007","unstructured":"Balkissoon D, Staines K, McCauley J, Wood J, Young J, Kaufman J, Butter C (2007) Low frequency of the Mx allele for viral resistance predates recent intensive selection in domestic chickens. Immunogenetics 59:687\u2013691","journal-title":"Immunogenetics"},{"key":"835_CR54","first-page":"1","volume":"B-3285","author":"KT Ramasamy","year":"2017","unstructured":"Ramasamy KT, Reddy MR, Raja Ravindra KS, Chatterjee RN (2017) Chicken Mx gene polymorphisms in Indian native chicken breeds and White Leghorn by real time multiplex allele specific PCR. Indian J Anim Res B-3285:1\u20133","journal-title":"Indian J Anim Res"},{"key":"835_CR55","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1186\/1753-6561-5-S4-S37","volume":"5","author":"T Sartika","year":"2011","unstructured":"Sartika T, Sulandari S, Zein MSA (2011) Selection of Mx gene genotype as genetic marker for Avian Influenza resistance in Indonesian native chicken. BMC Proc 5:S37","journal-title":"BMC Proc"},{"key":"835_CR56","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jgeb.2017.11.002","volume":"16","author":"MS Hassanane","year":"2018","unstructured":"Hassanane MS, Hassan AAM, Ahmed FM, El-Komy EM, Roushdy KM, Hassan NA (2018) Identification of Mx gene nucleotide dimorphism (G\/A) as genetic marker for antiviral activity in Egyptian chickens. J Genet Eng Biotechnol 16:83\u201388","journal-title":"J Genet Eng Biotechnol"},{"key":"835_CR57","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s00251-010-0509-1","volume":"63","author":"SJ Ewald","year":"2011","unstructured":"Ewald SJ, Kapczynski DR, Livant EJ, Suarez DL, Ralph J, McLeod S, Miller C (2011) Association of Mx1 Asn631 variant alleles with reductions in morbidity, early mortality, viral shedding, and cytokine responses in chickens infected with a highly pathogenic avian influenza virus. Immunogenetics 63:363\u2013375","journal-title":"Immunogenetics"}],"container-title":["Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13567-020-00835-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13567-020-00835-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13567-020-00835-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:10:01Z","timestamp":1631232601000},"score":1,"resource":{"primary":{"URL":"https:\/\/veterinaryresearch.biomedcentral.com\/articles\/10.1186\/s13567-020-00835-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,10]]},"references-count":57,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["835"],"URL":"https:\/\/doi.org\/10.1186\/s13567-020-00835-4","relation":{},"ISSN":["1297-9716"],"issn-type":[{"value":"1297-9716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,10]]},"assertion":[{"value":"15 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The experimental design was approved by the ethical Committee of <i>Institut de Recerca i Tecnologia Agroaliment\u00e0ries<\/i> (IRTA) and the Government of Catalonia (<i>Departament de Territori i Sostenibilitat, Direcci\u00f3 General de Pol\u00edtiques Ambientals i Medi Natural<\/i>) under reference code CEEA 18\/2017-9457.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"113"}}