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Isolation, Characterization, and Phylogenetic Analysis of Two New Crimean-Congo Hemorrhagic Fever Virus Strains from the Northern Region of Xinjiang Province, China

Virologica Sinica volume 33, pages 74–86 (2018)Cite this article

Abstract

Crimean-Congo hemorrhagic fever (CCHF) caused by the CCHF virus (CCHFV) is a tick-borne natural focal disease with a mortality rate of approximately 50%. CCHFV is widely prevalent in Africa, southern Asia, the Middle East, and southeast Europe. CCHF outbreaks have been reported previously in Xinjiang province, China, especially in its southern region. Epidemiological surveys conducted on ticks and animals have revealed the presence of CCHFV strains in ticks, rodents, and infected individuals from cities and counties in southern Xinjiang. Phylogenetic analyses revealed that the Chinese CCHFV strains belong to one genotype, based on complete sequences of the S segments of its negative-stranded RNA genome. The present study reports two new CCHFV strains isolated from Hyalomma asiaticum asiaticum ticks collected from Fukang City and Wujiaqu City in the northern region of Xinjiang. Viral characteristics and their evolutionary relationships were analyzed through metagenomic and reverse-transcription PCR analyses; these analyses indicated that the genotype of both strains was different from that of other Chinese strains. Furthermore, previous reports of CCHFV in Xinjiang were reviewed and phylogenetic analyses were performed. CCHFV was found to prevail in Fukang City in Junggar Basin for more than 20 years, and that Fukang City and Wujiaqu City are considered natural reservoirs of different genotypes of CCHFV strains. Our findings facilitate the understanding of CCHFV distribution in Xinjiang province and provide insights into the evolutionary relationships among Chinese CCHFV strains.

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References

  • Anagnostou V, Papa A (2009) Evolution of Crimean-Congo hemorrhagic fever virus. Infect Genet Evol 9:948–954

    Article  CAS  PubMed  Google Scholar 

  • Andersson I, Karlberg H, Mousavi-Jazi M, Martinez-Sobrido L, Weber F, Mirazimi A (2008) Crimean-Congo hemorrhagic fever virus delays activation of the innate immune response. J Med Virol 80:1397–1404

    Article  CAS  PubMed  Google Scholar 

  • Andersson C, Henriksson S, Magnusson KE, Nilsson M, Mirazimi A (2012) In situ rolling circle amplification detection of Crimean Congo hemorrhagic fever virus (CCHFV) complementary and viral RNA. Virology 426:87–92

    Article  CAS  PubMed  Google Scholar 

  • Bente DA, Forrester NL, Watts DM, McAuley AJ, Whitehouse CA, Bray M (2013) Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity. Antiviral Res 100:159–189

    Article  CAS  PubMed  Google Scholar 

  • Bukbuk DN, Fukushi S, Tani H, Yoshikawa T, Taniguchi S, Iha K, Fukuma A, Shimojima M, Morikawa S, Saijo M, Kasolo F, Baba SS (2014) Development and validation of serological assays for viral hemorrhagic fevers and determination of the prevalence of Rift Valley fever in Borno State, Nigeria. Trans R Soc Trop Med Hyg 108:768–773

    Article  CAS  PubMed  Google Scholar 

  • Bukbuk DN, Dowall SD, Lewandowski K, Bosworth A, Baba SS, Varghese A, Watson RJ, Bell A, Atkinson B, Hewson R (2016) Serological and virological evidence of Crimean-Congo haemorrhagic fever virus circulation in the human population of Borno State, Northeastern Nigeria. PLoS Negl Trop Dis 10:e0005126

    Article  PubMed  PubMed Central  Google Scholar 

  • Chai JJ (2004a) Preliminary report on survey of the distribution of hemorrhagic fever on the upper and middle reaches of the Tarim River. Endemic Dis Bull 19(suppl.):34–36 (in Chinese)

    Google Scholar 

  • Chai JJ, Han YY, Feng CH, Zhang YH, Nuer Y, Liu YH, Zhang YW, Qiao YS, Li HG (2004b) Report of investigation on hemorrhagic fever in Bachu County, Xinjiang in 1966. I. Clinical observation on 5 cases with hemorrhagic fever. Endemic Dis Bull 19(Suppl.):1–5 (in Chinese)

    Google Scholar 

  • Chai JJ, Nuer Y, Feng CH, Li HG, Liu J (2004c) Hemorrhagic fever in Bachu: Two cases report. Endemic Dis Bull 19(Suppl.):23–25 (in Chinese)

    Google Scholar 

  • Connolly-Andersen AM, Moll G, Andersson C, Akerstrom S, Karlberg H, Douagi I, Mirazimi A (2011) Crimean-Congo hemorrhagic fever virus activates endothelial cells. J Virol 85:7766–7774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dai X, Muhtar Feng CH, Sun SR, Tai XP, Wang XH, Burenmind Meng WW, Azat Zhang YJ (2006) Geography and host distribution of Crimean-Congo hemorrhagic fever in the Tarim Basin. Zhonghua Liu Xing Bing Xue Za Zhi 27:1048–1052

    CAS  PubMed  Google Scholar 

  • Ergonul O (2006) Crimean-Congo haemorrhagic fever. Lancet Infect Dis 6:203–214

    Article  PubMed  Google Scholar 

  • Feng CH, Bai XH, Liu HB, Li F, Gu Y (1991) Discovery of natural foci of Xinjiang hemorrhagic fever in the southern margin area of Junggar Basin, Xinjiang. Endemic Dis Bull 6:52–55 (in Chinese)

    Google Scholar 

  • Ferraris O, Moroso M, Pernet O, Emonet S, Ferrier Rembert A, Paranhos-Baccala G, Peyrefitte CN (2015) Evaluation of Crimean-Congo hemorrhagic fever virus in vitro inhibition by chloroquine and chlorpromazine, two FDA approved molecules. Antiviral Res 118:75–81

    Article  CAS  PubMed  Google Scholar 

  • Guo R, Shen S, Zhang Y, Shi J, Su Z, Liu D, Liu J, Yang J, Wang Q, Hu Z, Zhang Y, Deng F (2017) A new strain of Crimean-Congo hemorrhagic fever virus isolated from Xinjiang, China. Virol Sin 32:80–88

    Article  CAS  PubMed  Google Scholar 

  • Hoogstraal H (1979) The epidemiology of tick-borne Crimean-Congo hemorrhagic fever in Asia, Europe, and Africa. J Med Entomol 15:307–417

    Article  CAS  PubMed  Google Scholar 

  • Karlberg H, Tan YJ, Mirazimi A (2011) Induction of caspase activation and cleavage of the viral nucleocapsid protein in different cell types during Crimean-Congo hemorrhagic fever virus infection. J Biol Chem 286:3227–3234

    Article  CAS  PubMed  Google Scholar 

  • Liu YH, Chai JJ, Xiao CE, Li WH (2004) Epidemiological analysis of 140 cases with Xinjiang hemorrhagic fever. Endemic Dis Bull 19(Suppl.):47–49 (in Chinese)

    Google Scholar 

  • Messina JP, Pigott DM, Golding N, Duda KA, Brownstein JS, Weiss DJ, Gibson H, Robinson TP, Gilbert M, William Wint GR, Nuttall PA, Gething PW, Myers MF, George DB, Hay SI (2015) The global distribution of Crimean-Congo hemorrhagic fever. Trans R Soc Trop Med Hyg 109:503–513

    Article  PubMed  PubMed Central  Google Scholar 

  • Mohd Shukri M, Ling Kho K, Ghane Kisomi M, Lani R, Marlina S, Muhd Radzi SF, Tee Tay S, Ping Wong L, Awang Mahmud AB, Hassan Nizam QN, Abu Bakar S, Zandi K (2015) Seroprevalence report on tick-borne encephalitis virus and Crimean-Congo hemorrhagic fever virus among Malaysian’s farm workers. BMC Public Health 15:704

    Article  PubMed  PubMed Central  Google Scholar 

  • Muianga AF, Watson R, Varghese A, Chongo IS, Ali S, Monteiro V, Inalda F, Chelene I, Antonio V, Hewson R, Gudo ES (2017) First serological evidence of Crimean-Congo haemorrhagic fever in febrile patients in Mozambique. Int J Infect Dis 62:119–123

    Article  PubMed  Google Scholar 

  • Palomar AM, Portillo A, Santibanez S, Garcia-Alvarez L, Munoz-Sanz A, Marquez FJ, Romero L, Eiros JM, Oteo JA (2017) Molecular (ticks) and serological (humans) study of Crimean-Congo hemorrhagic fever virus in the Iberian Peninsula, 2013–2015. Enferm Infecc Microbiol Clin 35:344–347

    Article  PubMed  Google Scholar 

  • Papa A, Ma B, Kouidou S, Tang Q, Hang C, Antoniadis A (2002) Genetic characterization of the M RNA segment of Crimean Congo hemorrhagic fever virus strains, China. Emerg Infect Dis 8:50–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Papa A, Tsergouli K, Tsioka K, Mirazimi A (2017) Crimean-Congo hemorrhagic fever: tick–host–virus interactions. Front Cell Infect Microbiol 7:213

    Article  PubMed  PubMed Central  Google Scholar 

  • Rodrigues R, Paranhos-Baccala G, Vernet G, Peyrefitte CN (2012) Crimean-Congo hemorrhagic fever virus-infected hepatocytes induce ER-stress and apoptosis crosstalk. PLoS ONE 7:e29712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simon M, Johansson C, Lundkvist A, Mirazimi A (2009a) Microtubule-dependent and microtubule-independent steps in Crimean-Congo hemorrhagic fever virus replication cycle. Virology 385:313–322

    Article  CAS  PubMed  Google Scholar 

  • Simon M, Johansson C, Mirazimi A (2009b) Crimean-Congo hemorrhagic fever virus entry and replication is clathrin-, pH- and cholesterol-dependent. J Gen Virol 90:210–215

    Article  CAS  PubMed  Google Scholar 

  • Spengler JR, Patel JR, Chakrabarti AK, Zivcec M, Garcia-Sastre A, Spiropoulou CF, Bergeron E (2015) RIG-I mediates an antiviral response to Crimean-Congo hemorrhagic fever virus. J Virol 89:10219–10229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun S, Dai X, Aishan M, Wang X, Meng W, Feng C, Zhang F, Hang C, Hu Z, Zhang Y (2009) Epidemiology and phylogenetic analysis of Crimean-Congo hemorrhagic fever viruses in Xinjiang, China. J Clin Microbiol 47:2536–2543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tamura K, Stecher G, Peterson D, Filipski A, Kumar S (2013) MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol 30:2725–2729

    Article  CAS  Google Scholar 

  • Tang Q, Prehaud C, Bouloy M, Conghui Z (1999) Sequencing and analysis of S gene segment of XHFV. Chin J Microbiol Immunol 19:461–465 (in Chinese)

    CAS  Google Scholar 

  • Tang Q, Zhao XQ, Wang HY, Simayi B, Zhang YZ, Saijo M, Morikawa S, Liang GD, Kurane I (2005) Molecular epidemiology of Xinjiang hemorrhagic fever viruses. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 19:312–318 (in Chinese)

    PubMed  Google Scholar 

  • Wasfi F, Dowall S, Ghabbari T, Bosworth A, Chakroun M, Varghese A, Tiouiri H, Ben Jemaa M, Znazen A, Hewson R, Zhioua E, Letaief A (2016) Sero-epidemiological survey of Crimean-Congo hemorrhagic fever virus in Tunisia. Parasite 23:10

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou Z, Deng F, Han N, Wang H, Sun S, Zhang Y, Hu Z, Rayner S (2013a) Reassortment and migration analysis of Crimean-Congo haemorrhagic fever virus. J Gen Virol 94:2536–2548

    Article  CAS  PubMed  Google Scholar 

  • Zhou Z, Meng W, Deng F, Xia H, Li T, Sun S, Wang M, Wang H, Zhang Y, Hu Z (2013b) Complete genome sequences of two Crimean-Congo hemorrhagic fever viruses isolated in China. Genome Announc 1. pii:e00571-13

    Google Scholar 

Download references

Acknowledgements

This work was supported by the Science and Technology Basic Work Program (2013FY113500) and the National Key Research and Development Program (2016YFE0113500) from the Ministry of Science and Technology of China, as well as the European Union’s Horizon 2020 EVAg project (No 653316).

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Authors and Affiliations

  1. State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China

    Yanfang Zhang, Shu Shen, Yaohui Fang, Jinliang Liu, Zhengyuan Su, Jinhao Liang, Zhong Zhang, Qiaoli Wu, Zhihong Hu & Fei Deng

  2. The Center for Disease Control and Prevention of Xinjiang Uygur Autonomous’ Region, Ürümqi, 830002, Xinjiang, China

    Cheng Wang, Abulikemu Abudurexiti & Yujiang Zhang

Authors
  1. Yanfang Zhang
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  2. Shu Shen
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  3. Yaohui Fang
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  4. Jinliang Liu
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  5. Zhengyuan Su
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  6. Jinhao Liang
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  7. Zhong Zhang
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  8. Qiaoli Wu
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  9. Cheng Wang
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  10. Abulikemu Abudurexiti
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  11. Zhihong Hu
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  12. Yujiang Zhang
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  13. Fei Deng
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Contributions

YZ, JL, CW and AA collected and processed the ticks for the inoculation of suckling mice; YZ and JL performed the first mice inoculation and harvested the tissue samples; YZ and JL passaged the two virus strains on newborn mice; YZ, ZZ and QW performed the virus infection and analyzed the virus production on Vero cells; YZ, ZS, YF and SS analysis all the work; ZH, YZ and FD conceived of the study; YZ and SS wrote the manuscript; YZ and FD checked and finalized the manuscript.

Corresponding authors

Correspondence to Yujiang Zhang or Fei Deng.

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The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

Animal experiments in this study were approved by the ethics committees of Wuhan Institute of Virology, Chinese Academy of Sciences (Approval Number: WIVH01201501).

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Cite this article

Zhang, Y., Shen, S., Fang, Y. et al. Isolation, Characterization, and Phylogenetic Analysis of Two New Crimean-Congo Hemorrhagic Fever Virus Strains from the Northern Region of Xinjiang Province, China. Virol. Sin. 33, 74–86 (2018). https://doi.org/10.1007/s12250-018-0020-7

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  • DOI: https://doi.org/10.1007/s12250-018-0020-7

Keywords

  • Crimean-Congo hemorrhagic fever virus
  • Mice inoculation
  • Isolate
  • Genotypes
  • Phylogenetic analysis
  • Fukang city
  • Wujiaqu city