Virologica Sinica

, Volume 32, Issue 3, pp 235–244

Phylogenetic analysis based on mitochondrial DNA sequences of wild rats, and the relationship with Seoul virus infection in Hubei, China

  • Dong-Ying Liu
  • Jing Liu
  • Bing-Yu Liu
  • Yuan-Yuan Liu
  • Hai-Rong Xiong
  • Wei Hou
  • Zhan-Qiu Yang
Research Article


Seoul virus (SEOV), which is predominantly carried by Rattus norvegicus, is one of the major causes of hemorrhagic fever with renal syndrome (HFRS) in China. Hubei province, located in the central south of China, has experienced some of the most severe epidemics of HFRS. To investigate the mitochondrial DNA (mtDNA)-based phylogenetics of wild rats in Hubei, and the relationship with SEOV infection, 664 wild rats were captured from five trapping sites in Hubei from 2000–2009 and 2014–2015. Using reverse-transcription (RT)-PCR, 41 (6.17%) rats were found to be positive for SEOV infection. The SEOV-positive percentage in Yichang was significantly lower than that in other areas. The mtDNA D-loop and cytochrome b (cyt-b) genes of 103 rats were sequenced. Among these animals, 37 were SEOV-positive. The reconstruction of the phylogenetic relationship (based on the complete D-loop and cyt-b sequences) allowed the rats to be categorized into two lineages, R. norvegicus and Rattus nitidus, with the former including the majority of the rats. For both the D-loop and cyt-b genes, 18 haplotypes were identified. The geographic distributions of the different haplotypes were significantly different. There were no significant differences in the SEOVpositive percentages between different haplotypes. There were three sub-lineages for the D-loop, and two for cyt-b. The SEOV-positive percentages for each of the sub-lineages did not significantly differ. This indicates that the SEOV-positive percentage is not related to the mtDNA D-loop or cyt-b haplotype or the sub-lineage of rats from Hubei.


Seoul virus(SEOV) Rattus norvegicus mitochondrial DNA phylogenetic analysis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

12250_2016_3940_MOESM1_ESM.pdf (166 kb)
Phylogenetic analysis based on mitochondrial DNA sequences of wild rats, and the relationship with Seoul virus infection in Hubei, China


  1. Aplin KP, Chesser T, Ten Have J. 2003. Evolution biology of the genus Rattus: profile of an archetypal rodent pest. In: Rats, mice and people: rodent biology and management, Singleton GR, Hinds LA, Krebs CJ, et al. (eds). Canberra: Australian Centre for International Agriculture Research. pp 487–498.Google Scholar
  2. Avsic-Zupanc T, Saksida A, Korva M. 2015. Hantavirus infections. Clin Microbiol Infect, doi: 10.1111/1469-0691.12291.Google Scholar
  3. Barnett SA. 2002. The story of rats: their impact on us, and our impact on them. Australia: Allen and Uwin, Crows Nest. pp. 17–18.Google Scholar
  4. Bennett SN, Gu SH, Kang HJ, Arai S, Yanagihara R. 2014. Reconstructing the evolutionary origins and phylogeography of hantaviruses. Trends Microbiol, 22: 473–482.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Campo DS, Roh HJ, Pearlman BL, Fierer DS, Ramachandran S, Vaughan G, Hinds A, Dimitrova Z, Skums P, Khudyakov Y. 2016. Increased Mitochondrial Genetic Diversity in Persons Infected With Hepatitis C Virus. Cell Mol Gastroenterol Hepatol, 2: 676–684.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Cao S, Ma J, Cheng C, Ju W, Wang Y. 2016. Genetic characterization of hantaviruses isolated from rodents in the port cities of Heilongjiang, China, in 2014. BMC Vet Res, 12: 69.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Chang ZR, Lu L, Mao DQ, Pan HM, Feng LG, Yang XB, Liu FF, He YY, Zhang J, Yang WZ. 2016. Dynamics of Rodent and Rodent- borne Disease during Construction of the Three Gorges Reservoir from 1997 to 2012. Biomed Environ Sci, 29: 197–204.PubMedGoogle Scholar
  8. Charbonnel N, Pages M, Sironen T, Henttonen H, Vapalahti O, Mustonen J, Vaheri A. 2014. Immunogenetic factors affecting susceptibility of humans and rodents to hantaviruses and the clinical course of hantaviral disease in humans. Viruses, 6: 2214–2241.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Chen HX, Qiu FX, Dong BJ, Ji SZ, Li YT, Wang Y, Wang HM, Zuo GF, Tao XX, Gao SY. 1986a. Epidemiological studies on hemorrhagic fever with renal syndrome in China. J Infect Dis, 154: 394–398.CrossRefPubMedGoogle Scholar
  10. Chen HX, Qiu FX, Dong BJ, Ji SZ, Li YT, Wang Y, Wang HM, Zuo GF, Tao XX, Gao SY. 1986b. Epidemiological studies on hemorrhagic fever with renal syndrome in China. J Infect Dis, 154: 394–398.CrossRefPubMedGoogle Scholar
  11. Childs JE, Korch GW, Glass GE, LeDuc JW, Shah KV. 1987. Epizootiology of Hantavirus infections in Baltimore: isolation of a virus from Norway rats, and characteristics of infected rat populations. Am J Epidemiol, 126: 55–68.CrossRefPubMedGoogle Scholar
  12. Costa F, Porter FH, Rodrigues G, Farias H, de Faria MT, Wunder EA, Osikowicz LM, Kosoy MY, Reis MG, Ko AI, Childs JE. 2014. Infections by Leptospira interrogans, Seoul virus, and Bartonella spp. among Norway rats (Rattus norvegicus) from the urban slum environment in Brazil. Vector Borne Zoonotic Dis, 14: 33–40.PubMedGoogle Scholar
  13. Cueto GR, Cavia R, Bellomo C, Padula PJ, Suarez OV. 2008. Prevalence of hantavirus infection in wild Rattus norvegicus and R. rattus populations of Buenos Aires City, Argentina. Trop Med Int Health, 13: 46–51.CrossRefGoogle Scholar
  14. Dasgupta S, Hoque MO, Upadhyay S, Sidransky D. 2009. Forced cytochrome B gene mutation expression induces mitochondrial proliferation and prevents apoptosis in human uroepithelial SVHUC- 1 cells. Int J Cancer, 125: 2829–2835.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Dupinay T, Pounder KC, Ayral F, Laaberki MH, Marston DA, Lacote S, Rey C, Barbet F, Voller K, Nazaret N, Artois M, Marianneau P, Lachuer J, Fooks AR, Pepin M, Legras-Lachuer C, McElhinney LM. 2014. Detection and genetic characterization of Seoul virus from commensal brown rats in France. Virol J, 11: 32.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Fang C, Wei X, Wei Y. 2016. Mitochondrial DNA in the regulation of innate immune responses. Protein Cell, 7: 11–16.CrossRefPubMedGoogle Scholar
  17. Grzimek B. 1968. Animal life encyclopedia. New York, NY: Van Nostrand Reinhold, pp. 579.Google Scholar
  18. Guardado-Estrada M, Medina-Martinez I, Juarez-Torres E, Roman-Bassaure E, Macias L, Alfaro A, Alcantara-Vazquez A, Alonso P, Gomez G, Cruz-Talonia F, Serna L, Munoz-Cortez S, Borges-Ibanez M, Espinosa A, Kofman S, Berumen J. 2012. The Amerindian mtDNA haplogroup B2 enhances the risk of HPV for cervical cancer: de-regulation of mitochondrial genes may be involved. J Hum Genet, 57: 269–276.CrossRefPubMedGoogle Scholar
  19. Guo G, Sheng J, Wu X, Wang Y, Guo L, Zhang X, Yao H. 2016. Seoul virus in the Brown Rat (Rattus norvegicus) from Urumqi, Xinjiang, Northwest of China. J Wildl Dis, 52: 705–708.CrossRefPubMedGoogle Scholar
  20. Guo WP, Lin XD, Wang W, Tian JH, Cong ML, Zhang HL, Wang MR, Zhou RH, Wang JB, Li MH, Xu J, Holmes EC, Zhang YZ. 2013. Phylogeny and origins of hantaviruses harbored by bats, insectivores, and rodents. PLoS Pathog, 9: e1003159.CrossRefGoogle Scholar
  21. Gwak GY, Lee DH, Moon TG, Choi MS, Lee JH, Koh KC, Paik SW, Joh JW, Yoo BC. 2011. The correlation of hepatitis B virus pre-S mutation with mitochondrial D-loop mutations and common deletions in hepatocellular carcinoma. Hepatogastroenterology, 58: 522–528.CrossRefPubMedGoogle Scholar
  22. Hall TA. 1999. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl. Acids. Symp. Ser., 41: 95–98.Google Scholar
  23. Hedrich H. 2000. History, Strains and Models. In: The laboratory Rat (Handbook of Experimental Animals), Krinke GJ and Buton T (eds). London: Academic Press. pp. 1871–1895.Google Scholar
  24. Heyman P, Baert K, Plyusnina A, Cochez C, Lundkvist A, Esbroeck MV, Goossens E, Vandenvelde C, Plyusnin A, Stuyck J. 2009. Serological and genetic evidence for the presence of Seoul hantavirus in Rattus norvegicus in Flanders, Belgium.Google Scholar
  25. Scand J Infect Dis, 41: 51–56.Google Scholar
  26. Heyman P, Plyusnina A, Berny P, Cochez C, Artois M, Zizi M, Pirnay JP, Plyusnin A. 2004. Seoul hantavirus in Europe: first demonstration of the virus genome in wild Rattus norvegicus captured in France. Eur J Clin Microbiol Infect Dis, 23: 711–717.CrossRefPubMedGoogle Scholar
  27. Hu T, Fan Q, Hu X, Deng B, Chen G, Gu L, Li M, Zheng Y, Yuan G, Qiu W, Jiang X, Zhang F. 2015. Molecular and serological evidence for Seoul virus in rats (Rattus norvegicus) in Zhangmu, Tibet, China. Arch Virol, 160: 1353–1357.CrossRefPubMedGoogle Scholar
  28. Hugot JP, Gu SH, Feliu C, Ventur J, Ribas A, Dormion J, Yanagihara R, Nicolas V. 2014. Genetic Diversity of Talpa Europaea and Nova Hanta Virus (NVAV) in France. Bull Acad Vet Fr, 167.Google Scholar
  29. Ibrahim IN, Sudomo M, Morita C, Uemura S, Muramatsu Y, Ueno H, Kitamura T. 1996. Seroepidemiological survey of wild rats for Seoul virus in Indonesia. Jpn J Med Sci Biol, 49: 69–74.CrossRefPubMedGoogle Scholar
  30. Jin C, Qin D, Pan W, Wang Y, Zhang Y, Deng C, Zheng J. 2008. Micromammals of the Giantpithecus fauna from Sanhe Cave, Chongzuo, Guangxi. Quaternary Sciences, 28: 1129–1137. (In Chinese)Google Scholar
  31. Kang YJ, Zhou DJ, Tian JH, Yu B, Guo WP, Wang W, Li MH, Wu TP, Peng JS, Plyusnin A, Zhang YZ. 2012. Dynamics of hantavirus infections in humans and animals in Wuhan city, Hubei, China. Infect Genet Evol, 12: 1614–1621.CrossRefPubMedGoogle Scholar
  32. Kariwa H, Isegawa Y, Arikawa J, Takashima I, Ueda S, Yamanishi K, Hashimoto N. 1994. Comparison of nucleotide sequences of M genome segments among Seoul virus strains isolated from eastern Asia. Virus Res, 33: 27–38.CrossRefPubMedGoogle Scholar
  33. Komarov AP, Rokhlin OW, Yu CA, Gudkov AV. 2008. Functional genetic screening reveals the role of mitochondrial cytochrome b as a mediator of FAS-induced apoptosis. Proc Natl Acad Sci U S A, 105: 14453–14458.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG. 2007. Clustal W and Clustal X version 2.0. Bioinformatics, 23: 2947–2948.CrossRefPubMedGoogle Scholar
  35. Li JL, Ling JX, Liu DY, Liu J, Liu YY, Wei F, Luo F, Chen W, Zhang YH, Xiong HR, Hou W, Yang ZQ. 2012. Genetic characterization of a new subtype of Hantaan virus isolated from a hemorrhagic fever with renal syndrome (HFRS) epidemic area in Hubei Province, China. Arch Virol, 157: 1981–1987.CrossRefPubMedGoogle Scholar
  36. Librado P, Rozas J. 2009. DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics, 25: 1451–1452.CrossRefPubMedGoogle Scholar
  37. Lin XD, Guo WP, Wang W, Zou Y, Hao ZY, Zhou DJ, Dong X, Qu YG, Li MH, Tian HF, Wen JF, Plyusnin A, Xu J, Zhang YZ. 2012. Migration of Norway rats resulted in the worldwide distribution of Seoul hantavirus today. J Virol, 86: 972–981.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Liu J, Liu DY, Chen W, Li JL, Luo F, Li Q, Ling JX, Liu YY, Xiong HR, Ding XH, Hou W, Zhang Y, Li SY, Wang J, Yang ZQ. 2012. Genetic analysis of hantaviruses and their rodent hosts in central-south China. Virus Res, 163: 439–447.CrossRefPubMedGoogle Scholar
  39. Meerburg BG, Singleton GR, Kijlstra A. 2009. Rodent-borne diseases and their risks for public health. Crit Rev Microbiol, 35: 221–270.CrossRefPubMedGoogle Scholar
  40. Morzunov SP, Rowe JE, Ksiazek TG, Peters CJ, St Jeor SC, Nichol ST. 1998. Genetic analysis of the diversity and origin of hantaviruses in Peromyscus leucopus mice in North America. J Virol, 72: 57–64.PubMedPubMedCentralGoogle Scholar
  41. Neumann S, El Maadidi S, Faletti L, Haun F, Labib S, Schejtman A, Maurer U, Borner C. 2015. How do viruses control mitochondria- mediated apoptosis?. Virus Res, 209: 45–55.CrossRefPubMedGoogle Scholar
  42. Plyusnin A, Beaty Bj, Elliott RM, Goldbach R, Kormelink R, Lundkvist A, Schmaljohn CS, Tesh RB. 2012. Bunyaviridae. In: Virus Taxonomy: Classification and Nomenclature of Viruses. Ninth Report of the International Committee on Taxonomy of Viruses, King AMQ, Lefkowitz EJ, Adams MJ, et al. (eds). San Diego: Elsevier. pp. 725–741.Google Scholar
  43. Plyusnin A, Sironen T. 2014. Evolution of hantaviruses: co-speciation with reservoir hosts for more than 100 MYR. Virus Res, 187: 22–26.CrossRefPubMedGoogle Scholar
  44. Plyusnina A, Heyman P, Baert K, Stuyck J, Cochez C, Plyusnin A. 2012. Genetic characterization of seoul hantavirus originated from norway rats (Rattus norvegicus) captured in Belgium. J Med Virol, 84: 1298–1303.CrossRefPubMedGoogle Scholar
  45. Ramsden C, Holmes EC, Charleston MA. 2009. Hantavirus evolution in relation to its rodent and insectivore hosts: no evidence for codivergence. Mol Biol Evol, 26: 143–153.CrossRefPubMedGoogle Scholar
  46. Robinson R. 1965. Genetics of the Norway rats. Oxford, United Kingdom: Pergamon.Google Scholar
  47. Ronquist F, Huelsenbeck JP. 2003. MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics, 19: 1572–1574.CrossRefPubMedGoogle Scholar
  48. Ruggieri V, Mazzoccoli C, Pazienza V, Andriulli A, Capitanio N, Piccoli C. 2014. Hepatitis C virus, mitochondria and auto/mitophagy: exploiting a host defense mechanism.Google Scholar
  49. World J Gastroenterol, 20: 2624–2633.Google Scholar
  50. Schlegel M, Radosa L, Rosenfeld UM, Schmidt S, Triebenbacher C, Lohr PW, Fuchs D, Heroldova M, Janova E, Stanko M, Mosansky L, Fricova J, Pejcoch M, Suchomel J, Purchart L, Groschup MH, Kruger DH, Klempa B, Ulrich RG. 2012. Broad geographical distribution and high genetic diversity of shrewborne Seewis hantavirus in Central Europe. Virus Genes, 45: 48–55.CrossRefPubMedGoogle Scholar
  51. Schmidt S, Saxenhofer M, Drewes S, Schlegel M, Wanka KM, Frank R, Klimpel S, von Blanckenhagen F, Maaz D, Herden C, Freise J, Wolf R, Stubbe M, Borkenhagen P, Ansorge H, Eccard JA, Lang J, Jourdain E, Jacob J, Marianneau P, Heckel G, Ulrich RG. 2016. High genetic structuring of Tula hantavirus. Arch Virol, 161: 1135–1149.CrossRefPubMedGoogle Scholar
  52. Song G. 1999. Epidemiological progresses of hemorrhagic fever with renal syndrome in China. Chin Med J (Engl), 112: 472–477.Google Scholar
  53. Song Y, Lan Z, Kohn MH. 2014. Mitochondrial DNA phylogeography of the Norway rat. PLoS One, 9: e88425.CrossRefGoogle Scholar
  54. Torres-Perez F, Palma RE, Hjelle B, Ferres M, Cook JA. 2010. Andes virus infections in the rodent reservoir and in humans vary across contrasting landscapes in Chile. Infect Genet Evol, 10: 820–825.CrossRefPubMedGoogle Scholar
  55. Watson DC, Sargianou M, Papa A, Chra P, Starakis I, Panos G. 2014. Epidemiology of Hantavirus infections in humans: a comprehensive, global overview. Crit Rev Microbiol, 40: 261–272.CrossRefPubMedGoogle Scholar
  56. Wu X, Wang Y. 2012. Fossil materials and migrations of Mus musculus and Rattus norvegicus. Research of China's Frontier Archaeology, 11: 344–353.Google Scholar
  57. Yanagihara R, Gu SH, Arai S, Kang HJ, Song JW. 2014. Hantaviruses: rediscovery and new beginnings. Virus Res, 187: 6–14.CrossRefPubMedGoogle Scholar
  58. Yang Z, Yao P, Zhu H, Xu F, Yue M, Xie R, Sun Y, Xu Z, Wang C, Zhang Y. 2016. Co-divergence of hantavirus with its hosts' mithochondrial D-loop and cyt-b sequences. Chin J Public Health, 32: 205–207. (In Chinese)Google Scholar
  59. Zan J, Liu J, Zhou JW, Wang HL, Mo KK, Yan Y, Xu YB, Liao M, Su S, Hu RL, Zhou JY. 2016. Rabies virus matrix protein induces apoptosis by targeting mitochondria. Exp Cell Res, 347: 83–94.CrossRefPubMedGoogle Scholar
  60. Zhang S, Wang S, Yin W, Liang M, Li J, Zhang Q, Feng Z, Li D. 2014a. Epidemic characteristics of hemorrhagic fever with renal syndrome in China, 2006-2012. BMC Infect Dis, 14: 384.CrossRefPubMedPubMedCentralGoogle Scholar
  61. Zhang XF. 1990. Epidemiological survey of epidemic haemorrhagic fever in Xianning County. Chin J Prev Med, 24: 351–353. (In Chinese)Google Scholar
  62. Zhang YH, Ge L, Liu L, Huo XX, Xiong HR, Liu YY, Liu DY, Luo F, Li JL, Ling JX, Chen W, Liu J, Hou W, Zhang Y, Fan H, Yang ZQ. 2014b. The epidemic characteristics and changing trend of hemorrhagic fever with renal syndrome in Hubei Province, China. PLoS One, 9: e92700.CrossRefGoogle Scholar
  63. Zhang YZ. 2014. Discovery of hantaviruses in bats and insectivores and the evolution of the genus Hantavirus. Virus Res, 187: 15–21.CrossRefPubMedGoogle Scholar
  64. Zhang YZ, Zou Y, Fu ZF, Plyusnin A. 2010. Hantavirus infections in humans and animals, China. Emerg Infect Dis, 16: 1195–1203.CrossRefPubMedPubMedCentralGoogle Scholar
  65. Zhou JH, Zhang HL, Wang JL, Yang WH, Mi ZQ, Zhang YZ, Song XY, Hu QL, Dong YK, Pu WH, Hu HM, Gao LF, Yuan QH, Ya HX, Feng Y. 2009. Survey on host animal and molecular epidemiology of hantavirus in Chuxiong prefecture, Yunnan province. Chin J Epidemiol, 30: 239–242. (In Chinese)Google Scholar
  66. Zou Y, Hu J, Wang ZX, Wang DM, Li MH, Ren GD, Duan ZX, Fu ZF, Plyusnin A, Zhang YZ. 2008. Molecular diversity and phylogeny of Hantaan virus in Guizhou, China: evidence for Guizhou as a radiation center of the present Hantaan virus. J Gen Virol, 89: 1987–1997.CrossRefPubMedGoogle Scholar

Copyright information

© Wuhan Institute of Virology, CAS and Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.State Key Laboratory of Virology, Institute of Medical Virology, School of Basic Medical SciencesWuhan UniversityWuhanChina
  2. 2.Department of Microbiology, School of Basic Medical SciencesWuhan UniversityWuhanChina
  3. 3.School of Health SciencesWuhan UniversityWuhanChina

Personalised recommendations