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猫杯状病毒衣壳基因高变区在细胞培养和持续感染猫中的准种进化

Quasispecies evolution of a hypervariable region of the feline calicivirus capsid gene in cell culture and in persistently infected cats.

作者信息

Radford A D, Turner P C, Bennett M, McArdle F, Dawson S, Glenn M A, Williams R A, Gaskell R M

机构信息

Department of Veterinary Pathology, University of Liverpool, S. Wirral, UK.

出版信息

J Gen Virol. 1998 Jan;79 ( Pt 1):1-10. doi: 10.1099/0022-1317-79-1-1.

DOI:10.1099/0022-1317-79-1-1
PMID:9460915
Abstract

Feline calicivirus (FCV) is a respiratory pathogen of cats that is capable of causing persistent infections. This study examined the evolution of a hypervariable region of the FCV capsid gene both during 90 passages in cell culture and during replication in persistently infected cats. This region of the capsid protein is known to contain neutralization epitopes and may be a target for immune evasion during virus persistence in the host. Sequence analysis showed that FCV exists as a quasispecies which evolved both in cell culture and in persistently infected cats. Changes involved both loss of sequence present in the infecting isolate and a gain of both synonymous and non-synonymous nucleotide substitutions to generate sequences not detected within earlier isolates. Overall, these changes led to a reduction in population heterogeneity over time. Where virus populations were highly homogeneous allowing a consensus sequence to be determined, evolution rates for the consensus sequence ranged from 0.10-1.07 substitutions per nucleotide per year. Marked changes in virus neutralization profiles were seen in isolates obtained sequentially from a persistently infected cat. This was not the case with cell culture passaged virus, suggesting that the individual amino acid changes found only in virus from persistently infected cats may significantly alter the antigenic profile of FCV, and may be the result of immune selection.

摘要

猫杯状病毒(FCV)是猫的一种呼吸道病原体,能够引起持续性感染。本研究检测了FCV衣壳基因高变区在细胞培养90代过程中以及在持续感染猫体内复制过程中的进化情况。已知衣壳蛋白的这个区域含有中和表位,并且在病毒于宿主体内持续存在期间可能是免疫逃逸的靶点。序列分析表明,FCV以准种形式存在,在细胞培养和持续感染的猫体内均发生进化。变化包括感染分离株中存在的序列丢失,以及同义核苷酸替换和非同义核苷酸替换的增加,从而产生了早期分离株中未检测到的序列。总体而言,这些变化导致群体异质性随时间降低。在病毒群体高度同质从而能够确定共有序列的情况下,共有序列的进化速率为每年每核苷酸0.10 - 1.07个替换。从一只持续感染的猫中依次获得的分离株,其病毒中和谱出现了显著变化。而细胞培养传代病毒则未出现这种情况,这表明仅在持续感染猫的病毒中发现的个别氨基酸变化可能会显著改变FCV的抗原谱,并且可能是免疫选择的结果。

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