Recently Identified Mutations in the Ebola Virus-Makona Genome Do Not Alter Pathogenicity in Animal Models
Recently Identified Mutations in the Ebola Virus-Makona Genome Do Not Alter Pathogenicity in Animal Models
复制标题
DOI：
10.1016/j.celrep.2018.04.027
复制
发表时间：
2018-05-08
期刊：
影响因子：
8.8
通讯作者：
Feldmann, Heinz
中科院分区：
文献类型：
--
作者：
Marzi, Andrea;Chadinah, Spencer;Feldmann, Heinz
埃博拉病毒（EBOV），分离Makona，西非EBOV流行病的病原体，已成为许多研究的主题，以确定遗传多样性及其对病毒生物学，致病性和传播性的潜在影响。尽管随着时间的推移，通过多种人际传播链出现了各种突变，但其生物学相关性仍然值得怀疑。最近，糖蛋白GP和聚合酶L的突变，在爆发早期出现并稳定，与细胞培养中病毒适应性的改善有关。在这里，我们用携带或缺乏这些突变的EBOV-Makona分离株感染小鼠和恒河猴。令人惊讶的是，所有分离株的行为非常相似，独立于基因型，分别在小鼠和猕猴中引起严重或致命的疾病。同样，我们无法检测到病毒脱落差异的任何证据。因此，在两种动物模型中，没有特定的生物表型与这些EBOV-Makona突变相关。
Ebola virus (EBOV), isolate Makona, the causative agent of the West African EBOV epidemic, has been the subject of numerous investigations to determine the genetic diversity and its potential implication for virus biology, pathogenicity, and transmissibility. Despite various mutations that have emerged over time through multiple human-to-human transmission chains, their biological relevance remains questionable. Recently, mutations in the glycoprotein GP and polymerase L, which emerged and stabilized early during the outbreak, have been associated with improved viral fitness in cell culture. Here, we infected mice and rhesus macaques with EBOV-Makona isolates carrying or lacking those mutations. Surprisingly, all isolates behaved very similarly independent of the genotype, causing severe or lethal disease in mice and macaques, respectively. Likewise, we could not detect any evidence for differences in virus shedding. Thus, no specific biological phenotype could be associated with these EBOV-Makona mutations in two animal models.