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Hemorrhagic fever with renal syndrome (HFRS) is a debilitating disease of humans caused by Hantaan virus (HV), the prototype member´ of a newly proposed genus of Bunyaviridae. Studies of HV pathogenesis have been limited by the absence of a well defined model for a virus-induced disease state. In an attempt to devise a model for HV pathogenesis in laboratory rodents, newborn out bred suckling ICR mice were shown to be uniformly susceptible to lethal infection with non- mouse adapted HV by intracerebral (IC), intraperitoneal (IP), intramuscular (IM), and subcutaneous (SC) inoculation routes. Clinical courses, mean time to death, and fatal outcome were age-dependent. With an inoculums of 10 LDso, mortality was 100% in mice infected within 72h of birth, but declined to 50% by 7 days, By 2-2.5 weeks, animals developed complete resistance to clinical disease. Virus was consistently detected in serum by day 6 post-infection in IC- and IP- inoculated animals, and reached peak levels of 10´ PFU/ml by day 8: Mice infected IM and SC showed delays in onset of viremia, but achieved similar titers. Immunofluorescent antibody appeared by 17-18 days, and neutralizing antibody by 15 .days, in all experimental groups. Two of 8 inbred mouse strains were identified as resistant to clinical disease : SJL/J and A/J. Manipulation of this model will allow investigation of natural rodent pathogenesis with HV, as well ´as offer insight into disease mechanisms and therapy of HFRS.
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