Zhang Y Y, Summers J
Department of Molecular Genetics, The University of New Mexico School of Medicine, Albuquerque, New Mexico.
J Virol. 2000 Jun;74(11):5257-65. doi: 10.1128/jvi.74.11.5257-5265.2000.
The dynamic state of infection of 11 ducks with the duck hepatitis B virus was investigated. Chronic infections were established in newly hatched ducklings by inoculation with a mixture of wild-type virus and a mutant virus with a partial replication defect. As expected, the wild-type virus was rapidly enriched in the virus population during the spread of infection. Enrichment thereafter was correlated with normal growth of the liver, with the average mutant-to-wild-type ratio stabilizing for at least 2 months beyond the time at which the liver mass stabilized. Using experimentally determined growth rates for the mutant and wild-type viruses, we estimated that after the spread of infection, competition between the two virus strains was limited by the amount of replication required to infect new hepatocytes in the growing livers. The results suggest that, in a chronically infected liver, the selection of variants with a replication rate advantage is inefficient and that the emergence of such variants would depend on induced liver cell turnover, such as that occurring during chronic hepatitis.
研究了11只鸭感染鸭乙型肝炎病毒的动态情况。通过接种野生型病毒和具有部分复制缺陷的突变病毒混合物,在新孵化的雏鸭中建立了慢性感染。正如预期的那样,在感染传播过程中,野生型病毒在病毒群体中迅速富集。此后的富集与肝脏的正常生长相关,在肝脏质量稳定后的至少2个月内,突变型与野生型的平均比例保持稳定。利用实验确定的突变型和野生型病毒的生长速率,我们估计在感染传播后,两种病毒株之间的竞争受到感染生长中肝脏新肝细胞所需复制量的限制。结果表明,在慢性感染的肝脏中,具有复制速率优势的变体的选择效率低下,而此类变体的出现将取决于诱导型肝细胞更新,例如慢性肝炎期间发生的肝细胞更新。