Lemon S M, Binn L N, Marchwicki R, Murphy P C, Ping L H, Jansen R W, Asher L V, Stapleton J T, Taylor D G, LeDuc J W
Department of Medicine, University of North Carolina, Chapel Hill 27599-7030.
J Infect Dis. 1990 Jan;161(1):7-13. doi: 10.1093/infdis/161.1.7.
Six seronegative owl monkeys were intravenously inoculated with an antigenic variant (S18) of hepatitis A virus that is highly adapted to growth in cell culture and resists neutralization by monoclonal antibodies due to replacement of aspartic acid 70 of capsid protein VP3 with histidine. Each developed hepatitis 22-33 days after inoculation. Virus in feces, serum, and liver was quantified by radioimmunofocus assay. Viremia developed 7-11 days after inoculation, in parallel with fecal shedding of virus, and persisted for a mean of 20.5 days. Although the antigenic variant was recovered from feces or liver of three animals, virus in liver at the time of enzyme elevations was predominantly wild-type antigenic phenotype. Virus was not recovered from liver 96 days after challenge. These studies further define virologic events in hepatitis A and show that in vivo replication of an antigenic variant was restricted compared with that of wild-type virus.
六只血清学阴性的夜猴经静脉接种甲型肝炎病毒的一种抗原变异株(S18),该变异株高度适应细胞培养生长,并且由于衣壳蛋白VP3的70位天冬氨酸被组氨酸取代而抵抗单克隆抗体的中和作用。每只夜猴在接种后22 - 33天发生肝炎。通过放射免疫聚焦试验对粪便、血清和肝脏中的病毒进行定量。接种后7 - 11天出现病毒血症,与病毒的粪便排出同时发生,并持续平均20.5天。虽然从三只动物的粪便或肝脏中分离出了抗原变异株,但在酶升高时肝脏中的病毒主要是野生型抗原表型。攻毒96天后未从肝脏中分离到病毒。这些研究进一步明确了甲型肝炎中的病毒学事件,并表明与野生型病毒相比,抗原变异株在体内的复制受到限制。