Genetic and antigenic variation of foot-and-mouth disease virus during persistent infection in naturally infected cattle and Asian buffalo in India
Genetic and antigenic variation of foot-and-mouth disease virus during persistent infection in naturally infected cattle and Asian buffalo in India
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DOI：
10.1371/journal.pone.0214832
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发表时间：
2019-06-21
期刊：
影响因子：
3.7
通讯作者：
Arzt, Jonathan
中科院分区：
文献类型：
--
作者：
Biswal, Jitendra K.;Ranjan, Rajeev;Arzt, Jonathan
口蹄疫病毒（FMDV）持续感染的反刍动物在引发新的疫情中的作用仍然存在争议，并且这种动物构成的感知威胁阻碍了口蹄疫流行国家的国际贸易。在这项研究中，我们报告了在印度一个有组织的奶牛场自然发生的持续感染期间，口蹄疫病毒血清型O/ME-SA/Ind2001d亚谱系的遗传和抗原变异的纵向分析。在整个采样期间，恢复期（临床后）和亚临床感染动物之间以及牛和水牛之间提取FMDV RNA的动物比例没有显著差异。然而，与牛相比，从水牛样本中分离出的传染性病毒比例更高，持续时间也更长。对回收病毒P1序列的分析表明，突变的固定率为1.816 × 10（-2）个取代/位点/年（s/s/y） （95% CI为1.362-2.31 × 10(-2) s/s/y）。然而，大多数点突变是过渡取代。在单个动物中，P1区域的平均dN/dS （omega）值在0.076至0.357之间变化，表明作用于病毒基因组的选择压力在单个动物之间存在很大差异。统计简约性分析表明，所有从携带动物身上分离的病毒均来源于暴发病毒。2D-VNT测定的抗原关系值显示，在载体状态下，载体动物内部和之间的抗原变异出现波动，这表明一些载体病毒已经与疫苗株提供的保护发生了实质性的差异。这项研究有助于了解在FMDV携带者状态下发生的宿主内和群体内进化的程度。
The role of foot-and-mouth disease virus (FMDV) persistently infected ruminants in initiating new outbreaks remains controversial, and the perceived threat posed by such animals hinders international trade in FMD-endemic countries. In this study we report longitudinal analyses of genetic and antigenic variations of FMDV serotype O/ME-SA/Ind2001d sublineage during naturally occurring, persistent infection in cattle and buffalo at an organised dairy farm in India. The proportion of animals from which FMDV RNA was recovered was not significantly different between convalescent (post-clinical) and sub-clinically infected animals or between cattle and buffalo across the sampling period. However, infectious virus was isolated from a higher proportion of buffalo samples and for a longer duration compared to cattle. Analysis of the P1 sequences from recovered viruses indicated fixation of mutations at the rate of 1.816 x 10(-2) substitution/site/year (s/s/y) (95% CI 1.362-2.31 x 10(-2) s/s/y). However, the majority of point mutations were transitional substitutions. Within individual animals, the mean dN/dS (omega) value for the P1 region varied from 0.076 to 0.357, suggesting the selection pressure acting on viral genomes differed substantially across individual animals. Statistical parsimony analysis indicated that all of the virus isolates from carrier animals originated from the outbreak virus. The antigenic relationship value as determined by 2D-VNT assay revealed fluctuation of antigenic variants within and between carrier animals during the carrier state which suggested that some carrier viruses had diverged substantially from the protection provided by the vaccine strain. This study contributes to understanding the extent of within-host and within-herd evolution that occurs during the carrier state of FMDV.