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实验进化使拉本斯堡病毒(RBGV)适应脊椎动物宿主。

Adaptation of Rabensburg virus (RBGV) to vertebrate hosts by experimental evolution.

机构信息

The Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, NY, USA.

The Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, NY, USA.

出版信息

Virology. 2019 Feb;528:30-36. doi: 10.1016/j.virol.2018.11.015. Epub 2018 Dec 13.

DOI:10.1016/j.virol.2018.11.015
PMID:30554071
Abstract

Rabensburg virus (RBGV; Flaviviridae, Flavivirus) has been classified as both a novel flavivirus and a unique lineage of West Nile virus (WNV). RBGV and WNV share approximately 76% sequence homology, yet RBGV does not replicate to high viral titers within vertebrate cell lines at physiological temperatures and has not been naturally isolated from a vertebrate host. These unique genetic and biological characteristics make RBGV a viable tool to identify the genetic determinants of flavivirus infectivity and fitness in vertebrate hosts. Using experimental evolution, we characterized mutated variants of RBGV that have altered capacity for infection and replication in various cell lines. Shared genetic differences within these variants were identified throughout the genome, with a large majority found in the NS3 and NS5 genes. Our results support a role for the replication complex in host utilization and suggest that epistatic interactions likely contribute to host-specific fitness and emergence.

摘要

拉本斯堡病毒(RBGV;黄病毒科,黄病毒属)已被归类为新型黄病毒和西尼罗河病毒(WNV)的独特谱系。RBGV 和 WNV 约有 76%的序列同源性,但 RBGV 在生理温度下不会在脊椎动物细胞系中复制到高病毒滴度,也没有从脊椎动物宿主中自然分离出来。这些独特的遗传和生物学特性使 RBGV 成为鉴定黄病毒在脊椎动物宿主中感染性和适应性的遗传决定因素的可行工具。使用实验进化,我们对感染和复制能力发生改变的 RBGV 突变变体进行了特征描述,在整个基因组中都发现了这些变体之间的共享遗传差异,其中绝大多数位于 NS3 和 NS5 基因中。我们的结果支持复制复合物在宿主利用中的作用,并表明上位性相互作用可能有助于宿主特异性适应性和出现。

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