Fish Ian, Stenfeldt Carolina, Palinski Rachel M, Pauszek Steven J, Arzt Jonathan
Foreign Animal Disease Research Unit, Plum Island Animal Disease Center, ARS, USDA, Orient Point, NY 11957, USA.
Oak Ridge Institute for Science and Education, PIADC Research Participation Program, Oak Ridge, TN 37830, USA.
Pathogens. 2020 Mar 12;9(3):208. doi: 10.3390/pathogens9030208.
Foot-and-mouth disease virus (FMDV) infects hosts as a population of closely related viruses referred to as a quasispecies. The behavior of this quasispecies has not been described in detail in natural host species. In this study, virus samples collected from vaccinated and non-vaccinated cattle up to 35 days post-experimental infection with FMDV A24-Cruzeiro were analyzed by deep-sequencing. Vaccination induced significant differences compared to viruses from non-vaccinated cattle in substitution rates, entropy, and evidence for adaptation. Genomic variation detected during early infection reflected the diversity inherited from the source virus (inoculum), whereas by 12 days post infection, dominant viruses were defined by newly acquired mutations. Mutations conferring recognized fitness gain occurred and were associated with selective sweeps. Persistent infections always included multiple FMDV subpopulations, suggesting distinct foci of infection within the nasopharyngeal mucosa. Subclinical infection in vaccinated cattle included very early bottlenecks associated with reduced diversity within virus populations. Viruses from both animal cohorts contained putative antigenic escape mutations. However, these mutations occurred during later stages of infection, at which time transmission is less likely to occur. This study improves upon previously published work by analyzing deep sequences of samples, allowing for detailed characterization of FMDV populations over time within multiple hosts.
口蹄疫病毒（FMDV）以一群被称为准种的密切相关病毒感染宿主。这种准种在自然宿主物种中的行为尚未得到详细描述。在本研究中，对实验感染A24 - 克鲁塞罗口蹄疫病毒后35天内从接种疫苗和未接种疫苗的牛采集的病毒样本进行了深度测序分析。与未接种疫苗的牛的病毒相比，疫苗接种在替换率、熵和适应性证据方面诱导了显著差异。早期感染期间检测到的基因组变异反映了从源病毒（接种物）继承的多样性，而到感染后12天，优势病毒由新获得的突变定义。赋予公认适应性增加的突变发生并与选择性清除相关。持续性感染总是包括多个FMDV亚群，表明鼻咽黏膜内存在不同的感染灶。接种疫苗的牛的亚临床感染包括与病毒群体内多样性降低相关的非常早期的瓶颈。来自两个动物队列的病毒都含有推定的抗原逃逸突变。然而，这些突变发生在感染后期，此时传播不太可能发生。本研究通过分析样本的深度序列改进了先前发表的工作，从而能够详细表征多个宿主中随时间变化的FMDV群体。
