Pathogenesis of Hantaan Virus Infection in Suckling Mice: Clinical, Virologic, and Serologic Observations

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  • U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21701

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 outbred 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 course, mean time to death, and fatal outcome were age-dependent. With an inoculum of 10 LD50, mortality was 100% in mice infected within 72 hr 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 ≃ 105 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.

Author Notes

Present address: Department of Microbiology, Catholic Medical College, 505 Banpo-Dong, Kangnam-Ku, Seoul, 135 Korea.