Abstract
Swine influenza presents a very important health and economic issue in pig productions worldwide. Viruses that cause the disease are genetically very diverse but usually belong to the H1N1, H1N2 and H3N2 subtype of influenza A viruses. In this study, we sequenced and analyzed the full genome of viruses detected in swine from seven commercial farms. Through the analysis of the complete sequences of internal gene cassette together with previously characterized HA and NA genes we found three different genotypes amongst five completely sequenced viruses. Two viruses possessed a completely H1avN1 genotype (40%) and belonged to the H1avN1 lineage, which is prevalent in European swine populations. The other three viruses have arisen through the reassortment of the genes of H1avN1 and H1N1pdm09 lineages. In one sample we detected coinfection with viruses of H3N2 subtype with genes of H1avN1, H1N1pdm09 and A/swine/Gent/1/1984-like H3N2 lineages that presents a potential environment for the generation of a triple reassortant virus. The presence of the H1N1pdm09 origin M gene in this sample implies the potential risk of the introduction of these viruses into the human population. Phylogenetic analysis of internal gene cassette revealed slower evolution within genes of H1N1pdm09 lineage than those of H1avN1 lineage.
References
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Schicker R.S., Rossow J., Eckel S., Fisher N., Bidol S., Tatham L., Matthews-Greer J., Sohner K., Bowman S.A., Avrill J., Forshey T., Blanton L., Davis C.T., Schiltz J., Skorupski S., Berman LS., Jang Y., Bresee S.J., Lindstrom S., Trock C.S., Wentworth D., Fry M.A., de Fijter S., Signs K., DiOrio M., Olsen J.S. & Biggerstaff M. 2016. Outbreak of influenza A(H3N2) variant virus infections among persons attending agricultural fairs housing infected swine — Michigan and Ohio, July–August 2016. Morb Mortal Wkly Rep, 65, 1157–1160.
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Tamura K. & Nei M. 1993. Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. Mol Biol Evol, 10, 512-526.
Van Reeth K., Brown H.I. & Olsen W.C. 2012. Influenza Virus. In Diseases of Swine, 10th Ed (J.J. Zimmerman, A.L. Karriker, A. Ramirez, J.K. Schwartz & W.G. Stevenson, eds). Wiley-Blackwell Publishing, United Kingdom, 557-571.
Vincent L.A., Lewis N. & Webby R. 2017. Global evolution of influenza A viruses in swine. In Animal influenza, 2nd Ed. (E.D. Swayne, editor). Wiley-Blackwell Publishing, United Kingdom, 459-479.
Watson S. J., Langat P., Reid M. S., Tsan-Yuk Lam T., Cotten M., Kelly M., Van Reeth K., Qiu Y., Simon G., Bonin E., Foni E., Chiapponi C., Larsen L., Hjulsager C., Markowska-Daniel I., Urbaniak K., Dürrwald R., Schlegel M., Huovilainen A., Davidson I., Dán A., Loeffen W., Edwards S., Bublot M., Vila T., Maldonado J., Valls L., ESNIP3 Consortium, Brown H. I., Pybus O. G. & Kellama P. 2015. Molecular epidemiology and evolution of influenza viruses circulating within European swine between 2009 and 2013. J virol, 89(19), 9920-9931.
Welsh D. M., Baird M. P., Guelbenzu-Gonzalo P. M., Hanna A., Reid M. S., Essen S., Russell C., Thomas S., Barrass L., McNeilly F., McKillen J., Todd D., Harkin V., McDowell S., Choudhury B., Irvine M. R., Borobia J., Grant J. & Brown H. I. 2010. Initial incursion of pandemic (H1N1) 2009 influenza A virus into European pigs. Vet Rec, 166, 642-645.
WHO. 2012. Report of the WHO Pandemic Influenza A(H1N1) Vaccine Deployment Initiative.
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Zell R., Groth M., Krumbholz A., Lange J., Philipps A. & Durrwald R. 2020. Novel reassortant swine H3N2 influenza A viruses in Germany. Sci Rep, 10. 14296 (2020). https://doi.org/10.1038/s41598-020-71275-5.
Zell R., Scholtissek C. & Ludwig S. 2013. Genetics, evolution, and the zoonotic capacity of European swine influenza viruses. In Swine influenza. (A.J. Richt & J.R. Webby, eds) Springer, USA. 370: 29–55.
Zhou N.N., Senne D.A., Landgraf J.S., Swenson S.L., Erickson G., Rossow K., Liu L., Yoon Kj., Krauss S. & Webster R.G. 1999. Genetic reassortment of avian, swine, and human influenza A viruses in American pigs. J Virol, 73(10), 8851-6.
Bowman S. A., Nelson W. S., Page L. S., Nolting M. J., Killian L. M., Sreevatsan S. & Slemons D. R. 2014. Swine-to-human transmission of influenza A(H3N2) virus at agricultural fairs, Ohio, USA, 2012.
Emerg Infect Dis, 20(9), 1472-1480.
Brown, H. I. 2000. The epidemiology and evolution of influenza viruses in pigs. Vet Microbiol, 74, 29-46.
Chauhan, P. R. & Gordon, L. M. 2020. A systematic review analyzing the prevalence and circulation of influenza viruses in swine population worldwide. Pathogens, 9 (5), 335.
Chepkwony S., Parys A., Vandoorn E., Stadejek W., Xie J., King J., Graaf A., Pohlmann A., Beer M., Harder T. & Van Reeth K. 2021. Genetic and antigenic evolution of H1 swine influenza A viruses isolated in Belgium and the Netherlands from 2014 through 2019. Sci Rep, 11(1):11276. doi: 10.1038/s41598-021-90512-z. PMID: 34050216; PMCID: PMC8163766.
Chou Y. Y., Albrecht R. A., Pica N., Lowen A. C., Richt J. A., García-Sastre A., Palese P. & Hai R. 2011. The M segment of the 2009 new pandemic H1N1 influenza virus is critical for its high transmission efficiency in the guinea pig model. J virol, 85(21), 11235–11241. https://doi.org/10.1128/JVI.05794-11
Danilenko D.M., Komissarov A.B., Fadeev A.V., Bakaev M.I., Ivanova A.A., Petrova P.A., Vassilieva A.D., Komissarova K.S., Zheltukhina A.I., Konovalova N.I. & Vasin A.V. 2021. Antigenic and genetic characterization of swine influenza viruses identified in the European region of Russia, 2014-2020. Front Microbiol, 12:662028. doi: 10.3389/fmicb.2021.662028. PMID: 33936018; PMCID: PMC8081852.
Đurišić S., Milanov D. & Petrović T. 2005.Influenza A infections in animals and birds and their significance in the epidemiology of human influenza-a. Vet glas, 59(3-4), 405 - 418.
Felsenstein J. 1985. Confidence limits on phylogenies: An approach using the bootstrap. Evol, 39(4), 783–791. https://doi.org/10.2307/2408678
Finelli L. & Swerdlow L. D. 2013. The emergence of influenza A (H3N2) virus: What we learned from the first wave. Clin Infect Dis, 57(Suppl 1): S1–S3. doi:10.1093/cid/cit324.
Henritzi D., Petric P.P., Lewis N.S., Graaf A., Pessia A., Starick E., Breithaupt A., Strebelow G., Luttermann C., Parfker L.M.K., Schröder C., Hammerschmidt B., Herrler G., Beilage E.G., Stadlbauer D., Simon V., Krammer F., Wacheck S., Pesch S., Schwemmle M., Beer M. & Harder T.C. 2020. Surveillance of European domestic pigpopulations identifies an emerging reservoir of potentially zoonotic swine influenza A viruses. Cell Host Microb, 28(4), 614-627.
Kumar S., Stecher G. & Tamura K. 2016. MEGA7: Molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol, 33(7), 1870–1874.
Lycett J.S., Baillie G., Coulter E., Bhatt S., Kellam P., McCauley W.J., Wood N.L.J., Brown H.I., Pybus G.O. & Leigh Brown J.A. 2012. Estimating reassortment rates in co-circulating Eurasian swine influenza viruses. J Gen Virol, 93, 2326–2336.
Ma, W. 2020. Swine influenza virus: Current status and challenge. Virus Res, 288 (2020) 198118.
Maksimović Zorić J., Milićević V., Stevančević O., Chiapponi C., Potkonjak A., Stojanac N., Kureljušić B., Veljović Lj., Radosavljević V. & Savić B. 2020. Phylogenetic analysis of HA and NA genes of swine influenza viruses in Serbia in 2016-2018. Acta Vet-Beograd, 70 (1), 110-125.
Nelson I. M., Stratton J., Killian M. L., Janas-Martindale A. & Vincent L. A. 2015. Continual reintroduction of human pandemic H1N1 influenza A viruses into swine in the United States, 2009 to 2014. J virol, 89, 6218 –6226. doi:10.1128/JVI.00459-15.
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. 2009. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med, 360, 2605-15.
Pensaert M., Ortis K., Vandeputte J., Kaplan M. M. & Bachmann A. P. 1981. Evidence for the natural transmission of influenza A virus from wild ducks to swine and its potential importance for man. Bull World Health Organ, 59(1), 75-78.
Savić B., Radanović O., Jovičić D., Nešić K., Ivanović S., Stevančević O., Cvetojević Đ. & Kasagić D. 2015. Survey of infectious agents associated with porcine respiratory disease complex (PRDC) in Serbian swine herds using polymerase chain reaction (PCR) detection. Acta Vet-Beograd, 65(1), 79-88.
Schicker R.S., Rossow J., Eckel S., Fisher N., Bidol S., Tatham L., Matthews-Greer J., Sohner K., Bowman S.A., Avrill J., Forshey T., Blanton L., Davis C.T., Schiltz J., Skorupski S., Berman LS., Jang Y., Bresee S.J., Lindstrom S., Trock C.S., Wentworth D., Fry M.A., de Fijter S., Signs K., DiOrio M., Olsen J.S. & Biggerstaff M. 2016. Outbreak of influenza A(H3N2) variant virus infections among persons attending agricultural fairs housing infected swine — Michigan and Ohio, July–August 2016. Morb Mortal Wkly Rep, 65, 1157–1160.
Sun H., Xiao Y., Liu J., Wang D., Li F., Wang C., Li C., Zhu J., Song J., Sun H., Jiang Z., Liu L., Zhang X., Wei K., Hou D., Pu J., Sun Y., Tong Q., Bi Y., Chang K.C., Liu S., Gao G. F. & Liu J. 2020. Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection. PNAS, 117(29), 17204-17210.
Tamura K. & Nei M. 1993. Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. Mol Biol Evol, 10, 512-526.
Van Reeth K., Brown H.I. & Olsen W.C. 2012. Influenza Virus. In Diseases of Swine, 10th Ed (J.J. Zimmerman, A.L. Karriker, A. Ramirez, J.K. Schwartz & W.G. Stevenson, eds). Wiley-Blackwell Publishing, United Kingdom, 557-571.
Vincent L.A., Lewis N. & Webby R. 2017. Global evolution of influenza A viruses in swine. In Animal influenza, 2nd Ed. (E.D. Swayne, editor). Wiley-Blackwell Publishing, United Kingdom, 459-479.
Watson S. J., Langat P., Reid M. S., Tsan-Yuk Lam T., Cotten M., Kelly M., Van Reeth K., Qiu Y., Simon G., Bonin E., Foni E., Chiapponi C., Larsen L., Hjulsager C., Markowska-Daniel I., Urbaniak K., Dürrwald R., Schlegel M., Huovilainen A., Davidson I., Dán A., Loeffen W., Edwards S., Bublot M., Vila T., Maldonado J., Valls L., ESNIP3 Consortium, Brown H. I., Pybus O. G. & Kellama P. 2015. Molecular epidemiology and evolution of influenza viruses circulating within European swine between 2009 and 2013. J virol, 89(19), 9920-9931.
Welsh D. M., Baird M. P., Guelbenzu-Gonzalo P. M., Hanna A., Reid M. S., Essen S., Russell C., Thomas S., Barrass L., McNeilly F., McKillen J., Todd D., Harkin V., McDowell S., Choudhury B., Irvine M. R., Borobia J., Grant J. & Brown H. I. 2010. Initial incursion of pandemic (H1N1) 2009 influenza A virus into European pigs. Vet Rec, 166, 642-645.
WHO. 2012. Report of the WHO Pandemic Influenza A(H1N1) Vaccine Deployment Initiative.
Yu H., Zhang GH., Hua RH., Zhang Q., Liu TQ., Liao M. & Tong GZ. 2007. Isolation and genetic analysis of human origin H1N1 and H3N2 influenza viruses from pigs in China. Biochem Biophys Res Commun, 356:91–96.
Zell R., Groth M., Krumbholz A., Lange J., Philipps A. & Durrwald R. 2020. Novel reassortant swine H3N2 influenza A viruses in Germany. Sci Rep, 10. 14296 (2020). https://doi.org/10.1038/s41598-020-71275-5.
Zell R., Scholtissek C. & Ludwig S. 2013. Genetics, evolution, and the zoonotic capacity of European swine influenza viruses. In Swine influenza. (A.J. Richt & J.R. Webby, eds) Springer, USA. 370: 29–55.
Zhou N.N., Senne D.A., Landgraf J.S., Swenson S.L., Erickson G., Rossow K., Liu L., Yoon Kj., Krauss S. & Webster R.G. 1999. Genetic reassortment of avian, swine, and human influenza A viruses in American pigs. J Virol, 73(10), 8851-6.