Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, United States.
Front Cell Infect Microbiol. 2018 Jul 11;8:240. doi: 10.3389/fcimb.2018.00240. eCollection 2018.
Genome reassortment in Lassa virus (LASV) has been reported in nature, but phenotypic consequences of this phenomenon are not well described. Here we characterize, both and , reassortment between 2 LASV strains: the prototypic 1976 Josiah strain and a more recently isolated 2015 Liberian strain. analysis showed that although cis- and trans-acting elements of viral RNA synthesis were compatible between strains, reassortants demonstrated different levels of viral replication. These differences were also apparent , as reassortants varied in pathogenicity in the guinea pig model of LASV infection. The reassortant variant containing the Josiah S segment retained the virulence of the parental Josiah strain, but the reassortant variant containing the S segment of the Liberian isolate was highly attenuated compared to both parental strains. Contrary to observations in reassortants between LASV and other arenavirus species, which suggest that L segment-encoded factors are responsible for virulence, these studies highlight a role for S segment-encoded virulence factors in disease, and also suggest that inefficient interactions between proteins of heterologous strains may limit the prevalence of reassortant LASV variants in nature.
拉沙病毒（LASV）的基因组重配已在自然界中被报道，但这种现象的表型后果尚未得到很好的描述。在这里，我们对两种 LASV 株之间的 和 重组进行了特征描述：原型 1976 年的 Josiah 株和最近分离出的 2015 年利比里亚株。分析表明，尽管病毒 RNA 合成的顺式和反式作用元件在株间是兼容的，但重组体表现出不同水平的病毒复制。这些差异在豚鼠 LASV 感染模型中也很明显，重组体在致病性方面存在差异。含有 Josiah S 节段的重组变体保留了亲本 Josiah 株的毒力，但含有利比里亚分离株 S 节段的重组变体与两个亲本株相比，毒力显著降低。与 LASV 和其他沙粒病毒属病毒之间重组体的观察结果相反，后者表明 L 节段编码的因子是毒力的决定因素，这些研究强调了 S 节段编码的毒力因子在疾病中的作用，并表明异源株之间蛋白的低效相互作用可能限制了重组 LASV 变体在自然界中的流行。
