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

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.

Accepted for publication August 11, 1984.

^* The views of the authors do not purport to reflect the positions of the Department of the Army or the Department of Defense.

In conducting the research described in this report, the investigators adhered to the Guide for the Care and Use of Laboratory Animals, as promulgated by the National Research Council. The facilities are fully accredited by the American Association for Accreditation of Laboratory Animal Care.

Address reprint requests to: Kelly T. McKee, Jr., M.D., Medical Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21701.

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

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