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

Hantaan virus(HTNV) causes hemorrhagic fever with renal syndrome(HFRS) with a case fatality rate ranging from <1 to 15 % in human. HantavaxR 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.