Pugh J C, Simmons H
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
J Virol. 1994 Apr;68(4):2487-94. doi: 10.1128/JVI.68.4.2487-2494.1994.
To test the hypothesis that in vivo resistance to hepadnavirus infection was due to resistance of host hepatocytes, we isolated hepatocytes from Muscovy ducklings and chickens, birds that have been shown to be resistant to duck hepatitis B virus (DHBV) infection, and attempted to infect them in vitro with virus from congenitally infected Pekin ducks. Chicken hepatocytes were resistant to infection, but we were able to infect approximately 1% of Muscovy duck hepatocytes in culture. Infection requires prolonged incubation with virus at 37 degrees C. Virus spread occurs in the Muscovy cultures, resulting in 5 to 10% DHBV-infected hepatocytes by 3 weeks after infection. The relatively low rate of accumulation of DHBV DNA in infected Muscovy hepatocyte cultures is most likely due to inefficient spread of virus infection; in the absence of virus spread, the rates of DHBV replication in Pekin and Muscovy hepatocyte cultures are similar. 5-Azacytidine treatment can induce susceptibility to DHBV infection in resistant primary Pekin hepatocytes but appears to have no similar effect in Muscovy cultures. The relatively inefficient infection of Muscovy duck hepatocytes that we have described may account for the absence of a detectable viremia in Muscovy ducklings experimentally infected with DHBV.
为了验证体内对嗜肝DNA病毒感染产生抗性是由于宿主肝细胞具有抗性这一假说,我们从番鸭和鸡中分离出肝细胞,这两种禽类已被证明对鸭乙型肝炎病毒(DHBV)感染具有抗性,并尝试在体外将来自先天性感染的北京鸭的病毒感染它们。鸡肝细胞对感染具有抗性,但我们能够在培养物中感染约1%的番鸭肝细胞。感染需要在37摄氏度下与病毒长时间孵育。病毒在番鸭培养物中传播,感染后3周时导致5%至10%的肝细胞被DHBV感染。在受感染的番鸭肝细胞培养物中,DHBV DNA积累率相对较低很可能是由于病毒感染传播效率低下;在没有病毒传播的情况下,北京鸭和番鸭肝细胞培养物中DHBV的复制率相似。5-氮杂胞苷处理可诱导抗性原代北京鸭肝细胞对DHBV感染产生易感性,但在番鸭培养物中似乎没有类似作用。我们所描述的番鸭肝细胞相对低效的感染情况可能解释了在实验感染DHBV的番鸭雏鸭中未检测到病毒血症的原因。