Arbovirus high fidelity variant loses fitness in mosquitoes and mice
Arbovirus high fidelity variant loses fitness in mosquitoes and mice
复制标题
DOI：
10.1073/pnas.1111650108
复制
发表时间：
2011-09-20
影响因子：
11.1
通讯作者：
Vignuzzi, Marco
中科院分区：
文献类型：
--
作者：
Coffey, Lark L.;Beeharry, Yasnee;Vignuzzi, Marco
RNA依赖性RNA聚合酶（RdRp）的错误率影响病毒RNA群体中的突变频率。使用基孔肯雅病毒（CHIKV），我们描述了一个独特的虫媒病毒保真度变异与一个单一的C483Y氨基酸的变化，在nsP4 RdRp，增加复制保真度，并产生人口减少遗传多样性。在蚊子中，高保真CHIKV呈现比野生型更低的感染和传播滴度。在新生小鼠中，高保真CHIKV会产生截短的病毒血症和较低的器官滴度。这些结果表明，增加的复制保真度和减少的遗传多样性对虫媒病毒在无脊椎动物和脊椎动物宿主中的适应性产生负面影响。
The error rate of RNA-dependent RNA polymerases (RdRp) affects the mutation frequency in a population of viral RNAs. Using chikungunya virus (CHIKV), we describe a unique arbovirus fidelity variant with a single C483Y amino acid change in the nsP4 RdRp that increases replication fidelity and generates populations with reduced genetic diversity. In mosquitoes, high fidelity CHIKV presents lower infection and dissemination titers than wild type. In newborn mice, high fidelity CHIKV produces truncated viremias and lower organ titers. These results indicate that increased replication fidelity and reduced genetic diversity negatively impact arbovirus fitness in invertebrate and vertebrate hosts.