Institute of Infectious Disease, Henan Center for Disease Control, Henan, China.
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
Sci Rep. 2017 Jun 13;7(1):3390. doi: 10.1038/s41598-017-03318-3.
Marburg virus (MARV) has caused outbreaks of filoviral hemorrhagic fever since its discovery in 1967. The largest and deadliest outbreak occurred in Angola in 2005, with 252 cases and 227 deaths. In 2014, we developed a mouse-adapted MARV, Angola variant through serial passaging in mice. The mouse-adapted MARV exhibits many of the hallmarks of MARV disease in humans. By applying deep-sequencing to every passage of the virus, we are able to study virus evolution in this host with surprising precision. We show that two regions go through substantial changes: the intergenic region between NP and VP35, as well as the first 100 amino acids of the VP40 protein. Our results also reveal that there were profound changes during the production of the final virus stock in cell culture. Overall, our results show that a handful of regions carry most of the mutations acquired during the adaptation of the virus to a new host and that many mutations become fixed very early during the adaptation process.
马尔堡病毒（MARV）自 1967 年发现以来，已引发了几次丝状病毒出血热疫情。2005 年在安哥拉发生的疫情是规模最大、死亡率最高的一次，共报告了 252 例病例，其中 227 例死亡。2014 年，我们通过在小鼠中连续传代，开发出了适应小鼠的 MARV 安哥拉变异株。适应小鼠的 MARV 在小鼠中表现出了许多人类 MARV 疾病的特征。通过对病毒的每个传代进行深度测序，我们能够以惊人的精度研究病毒在这种宿主中的进化。我们发现有两个区域发生了很大的变化：NP 和 VP35 之间的基因间区，以及 VP40 蛋白的前 100 个氨基酸。我们的结果还表明，在细胞培养中生产最终病毒储备时，发生了深刻的变化。总的来说，我们的结果表明，在病毒适应新宿主的过程中，少数几个区域携带了大部分获得的突变，并且许多突变在适应过程的早期就被固定下来。
