Browse > Article
http://dx.doi.org/10.9766/KIMST.2021.24.3.348

Establishment of a Lethal Animal Model of Hantaan Virus 76-118 Infection  

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)
Publication Information
Journal of the Korea Institute of Military Science and Technology / v.24, no.3, 2021 , pp. 348-355 More about this Journal
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
Hantaan Virus; Lethal Animal Model; $LD_{50}$; Mouse;
Citations & Related Records
연도 인용수 순위
  • Reference
1 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.   DOI
2 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.   DOI
3 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.   DOI
4 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.   DOI
5 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.
6 DH Kruger, G Schonrich, and B Klempa, "Human Pathogenic Hantaviruses and Prevention of Infection," Human Vaccine, Vol. 7, pp. 685-693, 2011.   DOI
7 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.
8 D Safronetz, H Ebihara, H Feldmann, JW Hooper, "The Syrian Hamster Model of Hantavirus Pulmonary Syndrome," Antiviral Research, Vol. 95, pp. 282-292, 2012.   DOI
9 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.   DOI
10 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.   DOI
11 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.   DOI
12 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.   DOI
13 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.   DOI
14 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.   DOI
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.   DOI