Journal of the Korea Institute of Military Science and Technology (한국군사과학기술학회지)

The Korea Institute of Military Science and Technology (한국군사과학기술학회)
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Establishment of a Lethal Animal Model of Hantaan Virus 76-118 Infection

한탄바이러스 76-118을 이용한 치사 동물모델 확립

  • Song, Young Jo (The 4th Research and Development Institute, Agency for Defense Development) ;
  • Yu, Chi Ho (The 4th Research and Development Institute, Agency for Defense Development) ;
  • Gu, Se Hun (Convergence Technology Collaboration Directorate, Agency for Defense Development) ;
  • Hur, Gyeung Haeng (The 4th Research and Development Institute, Agency for Defense Development) ;
  • Jeong, Seong Tae (The 4th Research and Development Institute, Agency for Defense Development)
  • 송영조 (국방과학연구소 제4기술연구본부) ;
  • 유치호 (국방과학연구소 제4기술연구본부) ;
  • 구세훈 (국방과학연구소 국방첨단기술연구원) ;
  • 허경행 (국방과학연구소 제4기술연구본부) ;
  • 정성태 (국방과학연구소 제4기술연구본부)
  • Received : 2020.08.26
  • Accepted : 2021.05.21
  • Published : 2021.06.05
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Abstract

Hantaan virus(HTNV) causes hemorrhagic fever with renal syndrome(HFRS) with a case fatality rate ranging from <1 to 15 % in human. HantavaxⓇ is a vaccine against the Hantavirus, which has been conditionally approved by the Ministry of Food and Drug Safety(MFDS). However, only 50 % of volunteers had neutralizing antibodies 1 year following the boost. Effective antiviral treatments against HTNV infection are limited. Hantaviruses generally cause asymptomatic infection in adult mice. On the other hand, infection of suckling and newborn mice with hantaviruses causes lethal neurological diesease or persistant infection, which is different from the disease in humans. The development of vaccines and antiviral strategies for HTNV has been partly hampered by the lack of an efficient lethal mouse model to evaluate the efficacy of the candidate vaccines or antivirals. In this report, we established a lethal mouse model for HTNV, which may facilitate in vivo studies on the evaluation of candidate drugs against HTNV. The median lethal dose value of HTNV was calculated by probit analysis of deaths occurring within two weeks. Five groups of ten ICR mice were injected intracranially with serial 2-fold dilutions (from 50 to 3.125 PFU/head) of HTNV. Mice injected with HTNV began to die at 8 days post-infection. The lethal dose required to kill 50 % of the mice (LD50) was calculated to be 2.365 PFU/head.

Keywords

Acknowledgement

본 논문은 국방과학연구소 과제(과제번호: 912664201)의 연구 산출물입니다.

References

  1. DH Kruger, G Schonrich, and B Klempa, "Human Pathogenic Hantaviruses and Prevention of Infection," Human Vaccine, Vol. 7, pp. 685-693, 2011. https://doi.org/10.4161/hv.7.6.15197
  2. JH Kuhn, et al., "2020 Taxonomic Update for Phylum Negarnaviricota(Riboviria: Orthornavirae), Including the Large Orders Bunyavirales and Mononegavirales," Archives of Virology, Vol. 165, pp. 3023-3072, 2020. https://doi.org/10.1007/s00705-020-04731-2
  3. JW Golden, CD Hammerbeck, EM Mucker, RL Brocato, "Animal Models for the Study of Rodent-Borned Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses," BioMed Research International, Vol. 2015, Article ID 793257, pp. 1-31, 2015.
  4. D Safronetz, H Ebihara, H Feldmann, JW Hooper, "The Syrian Hamster Model of Hantavirus Pulmonary Syndrome," Antiviral Research, Vol. 95, pp. 282-292, 2012. https://doi.org/10.1016/j.antiviral.2012.06.002
  5. H Jiang, H Du, LM Wang, PZ Wang, XF Bai XF, "Hemorrhagic Fever with Renal Syndrome: Pathognesis and Clinical Picture," Frontiers in Cellular and Infection Microbiology, Vol. 6, pp. 1-11, 2016. https://doi.org/10.3389/fcimb.2016.00001
  6. RL Brocato, CD Hammerbeck, TM Bell, JB Wells, LA Queen, JW Hooper, "A Lethal Disease Model for Hantavirus Pulmonary Syndrome in Immunosupressed Syrian Hamsters Infected with Sin Nombre Virus," Journal of Virology, Vol. 88, pp. 811-819, 2014. https://doi.org/10.1128/JVI.02906-13
  7. JW Hooper, AM Ferro, V Wahl-Jensen, "Immune Serum Produced by DNA Vaccination Protect Hamsters against Lethal Respiratiory Challenge with Andes Virus," Journal of Virology, Vol. 82, pp. 1332-1338, 2008. https://doi.org/10.1128/JVI.01822-07
  8. K Hardcastle, D Scott, D Safronetz, DL Brining, H Ebihara, H Feldmann, A LaCasse, "Laguna Negra Virus Infection Causes Hantavirus Pulmonary Syndrome in Turkish Hamsters(Mesocricetus brandti)," Veterinary Pathology, Vol. 53, pp. 182-189, 2016. https://doi.org/10.1177/0300985815570071
  9. D Safronetz, M Zivcec M, R LaCasse, F Feldmann, R Rosenke, D Long, E Haddock, D Brining, D Gardner, H Feldmann, H Ebihara, "Pathogenesis and Host Response in Syrian Hamsters Following Intranasal Infection with Andes Virus," PLoS Pathology, Vol. 7, pp. 1-15, 2011.
  10. JW Hooper, DM Custer, E Thompson, and CS Schmaljohn, "DNA Vaccination with the Hantaan Virus M Gene Protects Hamsters against Three of Four HFRS Hantaviruses and Dlicits a High-Titer Neutralizing Antibody Response in Rhesus Monkeys," Journal of Virology, Vol. 75, No. 18, pp. 8469-8477, 2001. https://doi.org/10.1128/JVI.75.18.8469-8477.2001
  11. G Schonrich, A Rang, N Lutteke, MJ Raftery, N Charbonnel, RG Ulrich, "Hantavirus-Induced Immunity in Rodent Reservoirs and Humans," Immunological Review, Vol. 225, pp. 163-189, 2008. https://doi.org/10.1111/j.1600-065X.2008.00694.x
  12. DH Chung, A Vastermark, JV Camp, R Mcallister, SK Remold, YK Chu, C Bruder, CB Jonsson, "The Murine Model for Hantaan Virus-Induced Lethal Disease Shows Two Distinct Paths in Viral Evolutionary Trajectory with and without Ribavirin Treatment," Journal of Virology, Vol. 87, pp. 10997-11007, 2013. https://doi.org/10.1128/JVI.01394-13
  13. D Wichmann, HJ Grone, M Frese et al., "Hantaan Virus Infection Causes an Acute Neurological Disease That is Fatal in Adult Laboratory Mice," Journal of Virology, Vol. 76, No. 17, pp. 8890-8899, 2002. https://doi.org/10.1128/JVI.76.17.8890-8899.2002
  14. J Klingstrom, J Hardestam, and A Lundkvist, "Dobrava, but not Saaremaa, Hantavirus is Lethal and Induces Nitric Oxide Production in Suckling Mice," Microbes and Infection, Vol. 8, No. 3, pp. 728-737, 2006. https://doi.org/10.1016/j.micinf.2005.09.010
  15. GR Kim and KT McKee Jr., "Pathogenesis of Hantaan Virus Infection in Suckling Mice: Clinical, Virologic, and Serologic Observations," The American Journal of Tropical Medicine and Hygiene, Vol. 34, No. 2, pp. 388-395, 1985. https://doi.org/10.4269/ajtmh.1985.34.388