McArthur Monica A, Xiao Shu-Yuan, Barrett Alan D T
Department of Microbiology, The University of Texas Medical Branch, Galveston TX 77555-0609, USA.
Virus Res. 2005 Jun;110(1-2):65-71. doi: 10.1016/j.virusres.2005.01.004.
Viscerotropic yellow fever virus (YFV) infection occurs primarily in humans and non-human primates. Lack of an appropriate small animal model of viscerotropic YFV infection has been a major deterrent to molecular studies of viscerotropism. A hamster model of viscerotropic YFV infection has recently been described; however, these studies have focused on hamster-viscerotropic strains of YFV (including Asibi hamster P7 virus) that caused outward clinical signs of infection and mortality. In order to map more closely the molecular determinants of viscerotropism in the hamster model, a second sequential series of seven liver-to-liver passages of Asibi virus was undertaken through hamsters to generate Asibi P7b virus. Asibi hamster P7b virus did not cause clinically detectable signs of YFV infection; however, high quantities of circulating virus were isolated from the serum, and microscopic evaluation of the liver and spleen demonstrated histopathological lesions consistent with YFV infection. The genomic sequence of Asibi P7b virus was determined and compared to wild-type Asibi virus and the lethal, hamster-viscerotropic Asibi P7 virus and found to differ by only two amino acids in the envelope protein, E-98 and E-331.
嗜内脏性黄热病毒（YFV）感染主要发生在人类和非人灵长类动物中。缺乏合适的嗜内脏性YFV感染小动物模型一直是嗜内脏性分子研究的主要障碍。最近描述了一种嗜内脏性YFV感染的仓鼠模型；然而，这些研究集中在导致明显感染临床症状和死亡的YFV仓鼠嗜内脏性毒株（包括阿西比仓鼠P7病毒）上。为了更精确地确定仓鼠模型中嗜内脏性的分子决定因素，通过仓鼠对阿西比病毒进行了第二轮连续七次肝对肝传代，以产生阿西比P7b病毒。阿西比仓鼠P7b病毒未引起YFV感染的临床可检测症状；然而，从血清中分离出了大量循环病毒，对肝脏和脾脏的显微镜评估显示出与YFV感染一致的组织病理学病变。测定了阿西比P7b病毒的基因组序列，并与野生型阿西比病毒以及致死性的仓鼠嗜内脏性阿西比P7病毒进行比较，发现包膜蛋白中仅E-98和E-331两个氨基酸不同。
