Taylor K L, Murphy P C, Asher L V, LeDuc J W, Lemon S M
United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, Frederick, Maryland.
J Infect Dis. 1993 Sep;168(3):592-601. doi: 10.1093/infdis/168.3.592.
The virulence of a clonally isolated, cell culture-adapted hepatitis A virus (HM175/p16) was assessed in 4 seronegative owl monkeys inoculated intravenously with 2.8 x 10(4) radioimmunofocus-forming units of virus. The virus was highly attenuated, even though its complete nucleotide sequence contains only 19 mutations from the wild-type genome. Only 3 monkeys developed antibodies to hepatitis A virus (only 2 within 96 days of virus inoculation). One monkey had viremia and significantly elevated serum aminotransferase levels. In this animal, maximum viremia and fecal shedding of virus occurred 30-33 days after inoculation. In contrast, in earlier studies of a related cell culture-adapted but still hepatovirulent virus (HM175/S18), viremia was documented in 6 of 6 animals and peak viremia and fecal shedding of virus occurred 18 or 19 days after intravenous inoculation of about one-tenth as much virus.
将一株克隆分离的、适应细胞培养的甲型肝炎病毒（HM175/p16）接种到4只静脉注射2.8×10⁴放射免疫聚焦形成单位病毒的血清阴性猫头鹰猴体内，评估其毒力。该病毒高度减毒，尽管其完整的核苷酸序列与野生型基因组相比仅含有19个突变。只有3只猴子产生了甲型肝炎病毒抗体（仅2只在接种病毒后96天内产生）。1只猴子出现病毒血症，血清转氨酶水平显著升高。在这只动物中，接种后30 - 33天出现最大病毒血症和病毒粪便排泄。相比之下，在早期对一种相关的适应细胞培养但仍具肝毒性的病毒（HM175/S18）的研究中，6只动物中有6只出现病毒血症，静脉注射约十分之一剂量的病毒后18或19天出现病毒血症峰值和病毒粪便排泄。
