DOI QR코드

DOI QR Code

역학과 유전학적 데이터를 이용한 한국에서 2014년 발생한 H5N8 조류독감 전염경로의 유추

Inferring transmission routes of avian influenza during the H5N8 outbreak of South Korea in 2014 using epidemiological and genetic data

  • 최상철 (성신여자대학교 지식서비스공과대학 바이오생명공학과)
  • Choi, Sang Chul (Department of Biotechnology, Sungshin Women's University)
  • 투고 : 2018.07.09
  • 심사 : 2018.08.21
  • 발행 : 2018.09.30

초록

최근 양계업에 막대한 피해를 끼치는 조류독감은 한국에서 수천억원의 거대한 경제적 손실을 초래하였다. 병원균의 전염경로를 파악할 수 있다면 막대한 손해를 끼치는 생물학적 피해의 확산을 막고 일부 지역으로 제한하는데 큰 도움이 될 것이다. 병원균 DNA 서열의 계통학적인 분석을 통하여 감염된 숙주들을 방향성이 있는 연결선으로 연관짓는 전염 계통수를 얻을 수 있다. 지난 10여년간 유전적 데이터뿐만 아니라 역학 데이터를 이용한 전염 계통수 추론의 방법론적 발전이 이루어졌다. 이에, 본 연구에서는 전염 계통수 추론 방법을 이용하여 지난 2014년 한국에 발병한 고병원성 조류독감 H5N8에서 유래한 DNA 서열을 재분석하였다. 당시, H5N8 바이러스는 전라북도에서 시작하여 지역적으로 접해있는 4개의 지역으로 확산되어 나갔던 것으로 알려져 있다. 전염 계통수를 추론하는 베이지언 통계 방법인 Markov chain Monte Carlo를 반복적으로 시행하고 이를 종합하여 철새 외래종과 국내종 조류 숙주들의 전염 계통수를 추정하였다. 비록 연결선의 불확실성은 높았으나 추정된 전염 계통수를 통하여 당시 H5N8 바이러스는 전라북도에서 시작하고 충청남도를 거쳐 경기도로 퍼져나간 것을 확인할 수 있었다. 사육하는 오리와 같은 국내종 조류는 전염 계통수의 말단 노드에 위치하는 것으로 추정되었다. 이러한 결과를 통하여 야생 철새종이 2014년 한국의 H5N8 조류독감의 감염 매개자로 주된 역할을 하였다는 것을 재확인하였다.

Avian influenza recently damaged the poultry industry, which suffered a huge economic loss reaching billions of U.S. dollars in South Korea. Transmission routes of the pathogens would help plan to control and limit the spread of the devastating biological tragedy. Phylogenetic analyses of pathogen's DNA sequences could sketch transmission trees relating hosts with directed edges. The last decade has seen the methodological development of inferring transmission trees using epidemiological as well as genetic data. Here, I reanalyzed the DNA sequence data that had originated in the highly pathogenic avian influenza H5N8 outbreak of South Korea in 2014. The H5N8 viruses spread geographically contiguously from the origin of the outbreak, Jeonbuk. The Jeonbuk origin viruses were known to spread to four provinces neighboring Jeonbuk. I estimated the transmission tree of the host domestic and migratory wild birds after combining multiple runs of Markov chain Monte Carlo using a Bayesian method for inferring transmission trees. The estimated transmission tree, albeit with a rather large uncertainty in the directed edges, showed that the viruses spread from Jeonbuk through Chungnam to Gyeonggi. Domestic birds of breeder or broiler ducks were estimated to appear to be at the terminal nodes of the transmission tree. This observation confirmed that migratory wild birds played an important role as one of the main infection mediators in the avian influenza H5N8 outbreak of South Korea in 2014.

키워드

참고문헌

  1. Alexander DJ. 2007. An overview of the epidemiology of avian influenza. Vaccine 25, 5637-5644. https://doi.org/10.1016/j.vaccine.2006.10.051
  2. Alkhamis MA, Moore BR, and Perez AM. 2015. Phylodynamics of H5N1 highly pathogenic avian influenza in Europe, 2005-2010: potential for molecular surveillance of new outbreaks. Viruses 7, 3310-3328. https://doi.org/10.3390/v7062773
  3. Baek YH, Pascua PNQ, Song MS, Park KJ, Kwon HI, Lee JH, Kim SY, Moon HJ, Kim CJ, and Choi YK. 2010. Surveillance and characterization of low pathogenic H5 avian influenza viruses isolated from wild migratory birds in Korea. Virus Res. 150, 119-128. https://doi.org/10.1016/j.virusres.2010.03.002
  4. Bouckaert R, Heled J, Kuhnert D, Vaughan T, Wu CH, Xie D, Suchard MA, Rambaut A, and Drummond AJ. 2014. BEAST 2: a software platform for Bayesian evolutionary analysis. PLoS Comput. Biol. 10, e1003537. https://doi.org/10.1371/journal.pcbi.1003537
  5. Chanock RH, Cockburn WC, Davenport FM, Dowdle WR, de St Groth SF, Fukumi H, Kilbourne ED, Schild GC, Schulman JL, Sohier R, et al. 1972. A revised system of influenza virus nomenclature: A report of the WHO study group on classification. Virology 47, 854-856. https://doi.org/10.1016/0042-6822(72)90580-6
  6. Cottam EM, Thebaud G, Wadsworth J, Gloster J, Mansley L, Paton DJ, King DP, and Haydon DT. 2008. Integrating genetic and epidemiological data to determine transmission pathways of foot-and-mouth disease virus. Proc. R Soc. B 275, 887-895. https://doi.org/10.1098/rspb.2007.1442
  7. de Jong JC, Claas ECJ, Osterhaus ADME, Webster RG, and Lim WL. 1997. A pandemic warning? Nature 389, 554.
  8. Didelot X, Fraser C, Gardy J, and Colijn C. 2017. Genomic infectious disease epidemiology in partially sampled and ongoing outbreaks. Mol. Biol. Evol. 34, 997-1007.
  9. Didelot X, Gardy J, and Colijn C. 2014. Bayesian inference of infectious disease transmission from whole-genome sequence data. Mol. Biol. Evol. 31, 1869-1879. https://doi.org/10.1093/molbev/msu121
  10. Drummond AJ, Suchard MA, Xie D, and Rambaut A. 2012. Bayesian phylogenetics with BEAUti and the BEAST 1.7. Mol. Biol. Evol. 29, 1969-1973. https://doi.org/10.1093/molbev/mss075
  11. Edgar RC. 2004. MUSCLE - a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5, 113. https://doi.org/10.1186/1471-2105-5-113
  12. Fouchier RAM, Munster V, Wallensten A, Bestebroer TM, Herfst S, Smith D, Rimmelzwaan GF, Olsen B, and Osterhaus ADME. 2005. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J. Virol. 79, 2814-2822. https://doi.org/10.1128/JVI.79.5.2814-2822.2005
  13. Hall M, Woolhouse M, and Rambaut A. 2015. Epidemic reconstruction in a phylogenetics framework: transmission trees as partitions of the node set. PLoS Comput. Biol. 11, e1004613. https://doi.org/10.1371/journal.pcbi.1004613
  14. Hill SC, Lee YJ, Song BM, Kang HM, Lee EK, Hanna A, Gilbert M, Brown IH, and Pybus OG. 2015. Wild waterfowl migration and domestic duck density shape the epidemiology of highly pathogenic H5N8 influenza in the Republic of Korea. Infect. Genet. Evol. 34, 267-277. https://doi.org/10.1016/j.meegid.2015.06.014
  15. Hinshaw VS, Webster RG, and Rodriguez RJ. 1979. Influenza A viruses: combinations of hemagglutinin and neuraminidase subtypes isolated from animals and other sources. Arch. Virol. 62, 281-290. https://doi.org/10.1007/BF01318102
  16. Janies D, Hill AW, Guralnick R, Habib F, Waltari E, and Wheeler WC. 2007. Genomic analysis and geographic visualization of the spread of avian influenza (H5N1). Syst. Biol. 56, 321-329. https://doi.org/10.1080/10635150701266848
  17. Jeong J, Kang HM, Lee EK, Song BM, Kwon YK, Kim HR, Choi KS, Kim JY, Lee HJ, Moon OK, et al. 2014. Highly pathogenic avian influenza virus (H5N8) in domestic poultry and its relationship with migratory birds in South Korea during 2014. Vet. Microbiol. 173, 249-257. https://doi.org/10.1016/j.vetmic.2014.08.002
  18. Kang HM, Jeong OM, Kim MC, Kwon JS, Paek MR, Choi JG, Lee EK, Kim YJ, Kwon JH, and Lee YJ. 2010. Surveillance of avian influenza virus in wild bird fecal samples from South Korea, 2003-2008. J. Wildl. Dis. 46, 878-888. https://doi.org/10.7589/0090-3558-46.3.878
  19. Kim HK, Jeong DG, and Yoon SW. 2017a. Recent outbreaks of highly pathogenic avian influenza viruses in South Korea. Clin. Exp. Vaccine Res. 6, 95-103. https://doi.org/10.7774/cevr.2017.6.2.95
  20. Kim HR, Lee YJ, Park CK, Oem JK, Lee OS, Kang HM, Choi JG, and Bae YC. 2012. Highly pathogenic avian influenza (H5N1) outbreaks in wild birds and poultry, South Korea. Emerg. Infect. Dis. 18, 480-483. https://doi.org/10.3201/1803.111490
  21. Kim YI, Park SJ, Kwon HI, Kim EH, Si YJ, Jeong JH, Lee IW, Nguyen HD, Kwon JJ, Choi WS, et al. 2017b. Genetic and phylogenetic characterizations of a novel genotype of highly pathogenic avian influenza (HPAI) H5N8 viruses in 2016/2017 in South Korea. Infect. Genet. Evol. 53, 56-67. https://doi.org/10.1016/j.meegid.2017.05.001
  22. Ku KB, Park EH, Yum J, Kim JA, Oh SK, and Seo SH. 2014. Highly pathogenic avian influenza A(H5N8) virus from waterfowl, South Korea, 2014. Emerg. Infect. Dis. 20, 1587-1588. https://doi.org/10.3201/eid2009.140390
  23. Kwon HI, Song MS, Pascua PNQ, Baek YH, Lee JH, Hong SP, Rho JB, Kim JK, Poo H, Kim CJ, et al. 2011. Genetic characterization and pathogenicity assessment of highly pathogenic H5N1 avian influenza viruses isolated from migratory wild birds in 2011, South Korea. Virus Res. 160, 305-315. https://doi.org/10.1016/j.virusres.2011.07.003
  24. Lee DH, Lee HJ, Lee YN, Park JK, Lim TH, Kim MS, Youn HN, Lee JB, Park SY, Choi IS, et al. 2011. Evidence of intercontinental transfer of North American lineage avian influenza virus into Korea. Infect. Genet. Evol. 11, 232-236. https://doi.org/10.1016/j.meegid.2010.09.012
  25. Li KS, Guan Y, Wang J, Smith GJD, Xu KM, Duan L, Rahardjo AP, Puthavathana P, Buranathai C, Nguyen TD, et al. 2004. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature 430, 209-213. https://doi.org/10.1038/nature02746
  26. Liu J, Xiao H, Lei F, Zhu Q, Qin K, Zhang XW, Zhang XL, Zhao D, Wang G, Feng Y, et al. 2005. Highly pathogenic H5N1 influenza virus infection in migratory birds. Science 309, 1206-1206. https://doi.org/10.1126/science.1115273
  27. Mahardika GN, Jonas M, Murwijati T, Fitria N, Suartha IN, Suartini IGAA, and Wibawan IWT. 2016. Molecular analysis of hemagglutinin-1 fragment of avian influenza H5N1 viruses isolated from chicken farms in Indonesia from 2008 to 2010. Vet. Microbiol. 186, 52-58. https://doi.org/10.1016/j.vetmic.2016.02.023
  28. Morelli MJ, Thebaud G, Chadoeuf J, King DP, Haydon DT, and Soubeyrand S. 2012. A Bayesian inference framework to reconstruct transmission trees using epidemiological and genetic data. PLoS Comput. Biol. 8, e1002768. https://doi.org/10.1371/journal.pcbi.1002768
  29. Nagy A, Vostinakova V, Pindova Z, Hornickova J, Cernikova L, Sedlak K, Mojzis M, Dirbakova Z, and Machova J. 2009. Molecular and phylogenetic analysis of the H5N1 avian influenza virus caused the first highly pathogenic avian influenza outbreak in poultry in the Czech Republic in 2007. Vet. Microbiol. 133, 257-263. https://doi.org/10.1016/j.vetmic.2008.07.013
  30. Nair H, Brooks WA, Katz M, Roca A, Berkley JA, Madhi SA, Simmerman JM, Gordon A, Sato M, Howie S, et al. 2011. Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Lancet 378, 1917-1930. https://doi.org/10.1016/S0140-6736(11)61051-9
  31. Nguyen T, Rivailler P, Davis CT, Thi Hoa D, Balish A, Hoang Dang N, Jones J, Thi Vui D, Simpson N, Thu Huong N, et al. 2012. Evolution of highly pathogenic avian influenza (H5N1) virus populations in Vietnam between 2007 and 2010. Virology 432, 405-416. https://doi.org/10.1016/j.virol.2012.06.021
  32. Olsen B, Munster VJ, Wallensten A, Waldenstrom J, Osterhaus ADME, and Fouchier RAM. 2006. Global patterns of influenza a virus in wild birds. Science 312, 384-388. https://doi.org/10.1126/science.1122438
  33. Osmani MG, Ward MP, Giasuddin M, Islam MR, and Kalam A. 2014. The spread of highly pathogenic avian influenza (subtype H5N1) clades in Bangladesh, 2010 and 2011. Prev. Vet. Med. 114, 21-27. https://doi.org/10.1016/j.prevetmed.2014.01.010
  34. Pybus OG, Suchard MA, Lemey P, Bernardin FJ, Rambaut A, Crawford FW, Gray RR, Arinaminpathy N, Stramer SL, Busch MP, et al. 2012. Unifying the spatial epidemiology and molecular evolution of emerging epidemics. Proc. Natl. Acad. Sci. USA 109, 15066-15071. https://doi.org/10.1073/pnas.1206598109
  35. Reperant LA, Kuiken T, and Osterhaus ADME. 2012. Influenza viruses: from birds to humans. Hum. Vaccin Immunother. 8, 7-16. https://doi.org/10.4161/hv.8.1.18672
  36. Sakoda Y, Ito H, Uchida Y, Okamatsu M, Yamamoto N, Soda K, Nomura N, Kuribayashi S, Shichinohe S, Sunden Y, et al. 2012. Reintroduction of H5N1 highly pathogenic avian influenza virus by migratory water birds, causing poultry outbreaks in the 2010-2011 winter season in Japan. J. Gen. Virol. 93, 541-550. https://doi.org/10.1099/vir.0.037572-0
  37. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, and Ideker T. 2003. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498-2504. https://doi.org/10.1101/gr.1239303
  38. Shin JH, Woo C, Wang SJ, Jeong J, An IJ, Hwang JK, Jo SD, Yu SD, Choi K, Chung HM, et al. 2015. Prevalence of avian influenza virus in wild birds before and after the HPAI H5N8 outbreak in 2014 in South Korea. J. Microbiol. 53, 475-480. https://doi.org/10.1007/s12275-015-5224-z
  39. Shu Y and McCauley J. 2017. GISAID: Global initiative on sharing all influenza data - from vision to reality. Euro Surveill. 22, 1-3.
  40. Sonnberg S, Webby RJ, and Webster RG. 2013. Natural history of highly pathogenic avian influenza H5N1. Virus Res. 178, 63-77. https://doi.org/10.1016/j.virusres.2013.05.009
  41. Theary R, San S, Davun H, Allal L, and Lu H. 2012. New outbreaks of H5N1 highly pathogenic avian influenza in domestic poultry and wild birds in Cambodia in 2011. Avian Dis. 56, 861-864. https://doi.org/10.1637/10195-041012-ResNote.1
  42. Tian H, Zhou S, Dong L, Van Boeckel TP, Cui Y, Newman SH, Takekawa JY, Prosser DJ, Xiao X, Wu Y, et al. 2015. Avian influenza H5N1 viral and bird migration networks in Asia. Proc. Natl. Acad. Sci. USA 112, 172-177. https://doi.org/10.1073/pnas.1405216112
  43. Uchida Y, Suzuki Y, Shirakura M, Kawaguchi A, Nobusawa E, Tanikawa T, Hikono H, Takemae N, Mase M, Kanehira K, et al. 2012. Genetics and infectivity of H5N1 highly pathogenic avian influenza viruses isolated from chickens and wild birds in Japan during 2010-11. Virus Res. 170, 109-117. https://doi.org/10.1016/j.virusres.2012.09.004
  44. World Health Organization. 1971. A revised system of nomenclature for influenza viruses. Bull. World Health Organ. 45, 119-124.
  45. Ypma RJF, van Ballegooijen WM, and Wallinga J. 2013. Relating phylogenetic trees to transmission trees of infectious disease outbreaks. Genetics 195, 1055-1062. https://doi.org/10.1534/genetics.113.154856

피인용 문헌

  1. 자동 분류 기술을 활용한 온라인 강의 평가 방법 vol.24, pp.4, 2018, https://doi.org/10.14352/jkaie.2020.24.4.291