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 congruent to 10(5) 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.
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D000367:Age Factors; D000818:Animals; D000833:Animals, Suckling; D000914:Antibodies, Viral / Q000096:biosynthesis; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005455:Fluorescent Antibody Technique; D006476:Orthohantavirus / Q000276:immunology; D006480:Hemorrhagic Fever with Renal Syndrome / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D007928:Lethal Dose 50; D051379:Mice; D008815:Mice, Inbred Strains; D009500:Neutralization Tests; D013997:Time Factors; D014766:Viremia
D000914:Antibodies, Viral