Tao Ying, Shi Mang, Chommanard Christina, Queen Krista, Zhang Jing, Markotter Wanda, Kuzmin Ivan V, Holmes Edward C, Tong Suxiang
Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, The University of Sydney, Sydney, Australia.
J Virol. 2017 Feb 14;91(5). doi: 10.1128/JVI.01953-16. Print 2017 Mar 1.
Bats harbor a large diversity of coronaviruses (CoVs), several of which are related to zoonotic pathogens that cause severe disease in humans. Our screening of bat samples collected in Kenya from 2007 to 2010 not only detected RNA from several novel CoVs but, more significantly, identified sequences that were closely related to human CoVs NL63 and 229E, suggesting that these two human viruses originate from bats. We also demonstrated that human CoV NL63 is a recombinant between NL63-like viruses circulating in bats and 229E-like viruses circulating in bats, with the breakpoint located near 5' and 3' ends of the spike (S) protein gene. In addition, two further interspecies recombination events involving the S gene were identified, suggesting that this region may represent a recombination "hot spot" in CoV genomes. Finally, using a combination of phylogenetic and distance-based approaches, we showed that the genetic diversity of bat CoVs is primarily structured by host species and subsequently by geographic distances. Understanding the driving forces of cross-species virus transmission is central to understanding the nature of disease emergence. Previous studies have demonstrated that bats are the ultimate reservoir hosts for a number of coronaviruses (CoVs), including ancestors of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human CoV 229E (HCoV-229E). However, the evolutionary pathways of bat CoVs remain elusive. We provide evidence for natural recombination between distantly related African bat coronaviruses associated with and sp. bats that resulted in a NL63-like virus, an ancestor of the human pathogen HCoV-NL63. These results suggest that interspecies recombination may play an important role in CoV evolution and the emergence of novel CoVs with zoonotic potential.
蝙蝠携带多种冠状病毒（CoV），其中几种与可导致人类严重疾病的人畜共患病原体有关。我们对2007年至2010年在肯尼亚采集的蝙蝠样本进行筛查，不仅检测到了几种新型冠状病毒的RNA，更重要的是，还鉴定出了与人类冠状病毒NL63和229E密切相关的序列，这表明这两种人类病毒起源于蝙蝠。我们还证明，人类冠状病毒NL63是在蝙蝠中传播的NL63样病毒与在蝙蝠中传播的229E样病毒之间的重组体，重组断点位于刺突（S）蛋白基因的5'和3'端附近。此外，还鉴定出另外两个涉及S基因的种间重组事件，这表明该区域可能是冠状病毒基因组中的一个重组“热点”。最后，通过系统发育和基于距离的方法相结合，我们表明蝙蝠冠状病毒的遗传多样性主要由宿主物种构成，其次是地理距离。了解跨物种病毒传播的驱动力对于理解疾病出现的本质至关重要。先前的研究表明，蝙蝠是多种冠状病毒（CoV）的最终宿主，包括严重急性呼吸综合征冠状病毒（SARS-CoV）、中东呼吸综合征冠状病毒（MERS-CoV）和人类冠状病毒229E（HCoV-229E）的祖先。然而，蝙蝠冠状病毒的进化途径仍然难以捉摸。我们提供了证据，证明与和种蝙蝠相关的远缘非洲蝙蝠冠状病毒之间发生了自然重组，产生了一种NL63样病毒，即人类病原体HCoV-NL63的祖先。这些结果表明，种间重组可能在冠状病毒进化以及具有人畜共患病潜力的新型冠状病毒出现中发挥重要作用。
