Foreign Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Plum Island Animal Disease Research Center, Greenport, New York, USA.
Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, USA.
mSphere. 2023 Jun 22;8(3):e0064322. doi: 10.1128/msphere.00643-22. Epub 2023 Apr 24.
Superinfection of cattle persistently infected with foot-and-mouth disease virus (FMDV), with a heterologous FMDV strain has been shown to generate novel recombinant viruses. In this study, we investigated the pathogenesis events within specific tissues associated with FMDV coinfections in cattle subjected to either simultaneous or serial exposure to two distinct strains of FMDV. Both strains of FMDV (one each of serotypes O and A) were similarly localized to the nasopharyngeal mucosa during the early stages of infection. However, while no recombinant FMDV genomes were recovered from simultaneously coinfected cattle, interserotypic recombinants were isolated from nasopharyngeal tissue samples obtained at 48 h after heterologous superinfection of a persistently infected FMDV carrier. Additionally, analysis of FMDV genomes obtained from replicate nasopharyngeal tissue samples demonstrated that adjacent segments of the mucosa were sometimes infected by distinct viruses, demonstrating a multifocal and heterogeneous distribution of FMDV infection during primary and persistent phases of infection. This work indicates that superinfection of FMDV carriers may be an important source of emergent recombinant strains of FMDV in areas where multiple strains are co-circulating. Foot-and-mouth disease (FMD) is a socioeconomically impactful livestock disease with a complex epidemiology and ecology. Although recombinant viruses have been identified in field samples, the mechanisms of emergence of those viruses have never been elucidated. This current study demonstrates how serial infection of cattle with two distinct serotypes of FMD virus (FMDV) leads to rapid generation of recombinant viruses in the upper respiratory tracts of infected animals. This finding is particularly relevant in relation to the management of persistently infected FMDV carrier cattle that can maintain subclinical FMDV infection for months to years after an initial infection. Such carrier animals may function as mixing vessels that facilitate the emergence of novel recombinant FMDV strains in areas where multiple virus strains are in circulation.
牛口蹄疫病毒（FMDV）持续性感染的继发感染，与异源 FMDV 株的感染，已被证实会产生新的重组病毒。在本研究中，我们研究了在特定组织中与 FMDV 混合感染相关的发病机制事件，这些牛只受到两种不同 FMDV 株的同时或连续暴露。两种 FMDV 株（每种血清型各一）在感染的早期阶段均类似地定位于鼻咽黏膜。然而，虽然同时感染的牛只中未回收重组 FMDV 基因组，但在持续性感染 FMDV 载体的异源超级感染后 48 小时获得的鼻咽组织样本中分离到了不同血清型的重组病毒。此外，对从重复获得的鼻咽组织样本中获得的 FMDV 基因组进行分析表明，黏膜的相邻节段有时被不同的病毒感染，这表明在原发性和持续性感染期间，FMDV 的感染呈多灶性和异质性分布。这项工作表明，在多个流行株同时循环的地区，FMDV 载体的继发感染可能是新兴 FMDV 重组株的重要来源。口蹄疫（FMD）是一种对社会经济有重大影响的牲畜疾病，具有复杂的流行病学和生态学。尽管已在田间样本中鉴定出重组病毒，但这些病毒的出现机制从未得到阐明。本研究目前表明，牛只连续感染两种不同血清型的 FMD 病毒（FMDV）如何导致感染动物的上呼吸道中快速产生重组病毒。这一发现与持续性感染 FMDV 载体牛只的管理特别相关，这些动物在初次感染后数月至数年内可维持亚临床 FMDV 感染。这些载体动物可能充当混合容器，促进在多个流行株同时循环的地区新型重组 FMDV 株的出现。
