Kim G R, McKee K T
Am J Trop Med Hyg. 1985 Mar;34(2):388-95. doi: 10.4269/ajtmh.1985.34.388.
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.
肾综合征出血热（HFRS）是由汉坦病毒（HV）引起的一种使人衰弱的疾病，HV是新提议的布尼亚病毒科一个属的原型成员。由于缺乏病毒诱导疾病状态的明确模型，对HV发病机制的研究受到限制。为了设计一种实验室啮齿动物中HV发病机制的模型，发现新生远交乳鼠通过脑内（IC）、腹腔内（IP）、肌肉内（IM）和皮下（SC）接种途径对非小鼠适应的HV致死感染均具有一致的易感性。临床病程、平均死亡时间和致命结局与年龄有关。接种10 LD50剂量时，出生后72小时内感染的小鼠死亡率为100%，但到7天时降至50%。到2 - 2.5周时，动物对临床疾病产生完全抵抗力。IC和IP接种的动物在感染后第6天血清中始终能检测到病毒，到第8天达到峰值水平，约为10(5) PFU/ml。IM和SC接种的小鼠病毒血症出现延迟，但达到相似滴度。所有实验组中，免疫荧光抗体在17 - 18天出现，中和抗体在15天出现。8个近交系小鼠品系中有2个被鉴定为对临床疾病具有抗性：SJL/J和A/J。
