Genomic characterization and infectivity of a novel SARS-like coronavirus in Chinese bats

SARS coronavirus (SARS-CoV), the causative agent of the large SARS outbreak in 2003, originated in bats. Many SARS-like coronaviruses (SL-CoVs) have been detected in bats, particularly those that reside in China, Europe, and Africa. To further understand the evolutionary relationship between SARS-CoV and its reservoirs, 334 bats were collected from Zhoushan city, Zhejiang province, China, between 2015 and 2017. PCR amplification of the conserved coronaviral protein RdRp detected coronaviruses in 26.65% of bats belonging to this region, and this number was influenced by seasonal changes. Full genomic analyses of the two new SL-CoVs from Zhoushan (ZXC21 and ZC45) showed that their genomes were 29,732 nucleotides (nt) and 29,802 nt in length, respectively, with 13 open reading frames (ORFs). These results revealed 81% shared nucleotide identity with human/civet SARS CoVs, which was more distant than that observed previously for bat SL-CoVs in China. Importantly, using pathogenic tests, we found that the virus can reproduce and cause disease in suckling rats, and further studies showed that the virus-like particles can be observed in the brains of suckling rats by electron microscopy. Thus, this study increased our understanding of the genetic diversity of the SL-CoVs carried by bats and also provided a new perspective to study the possibility of cross-species transmission of SL-CoVs using suckling rats as an animal model.

2003年引发大范围严重急性呼吸综合征（SARS）暴发的病原体——严重急性呼吸综合征冠状病毒（SARS-CoV），起源于蝙蝠。研究人员已在蝙蝠体内检出多种类SARS冠状病毒（SL-CoVs），其中尤以栖息于中国、欧洲及非洲的蝙蝠群体中检出率为高。为进一步阐明SARS-CoV与其自然宿主间的演化关联，研究团队于2015年至2017年间，在中国浙江省舟山市采集了334份蝙蝠样本。通过对保守的冠状病毒RNA依赖的RNA聚合酶（RdRp）基因进行聚合酶链式反应（PCR）扩增，研究人员在该区域26.65%的蝙蝠样本中检测到冠状病毒，且检出率受季节变化影响显著。对两株采自舟山的新型类SARS冠状病毒（ZXC21与ZC45）进行全基因组分析后发现，二者基因组长度分别为29732个核苷酸（nt）与29802个核苷酸，且均包含13个开放阅读框（ORFs）。序列比对结果显示，这两株病毒与人类/果子狸SARS冠状病毒的核苷酸同源性为81%，其亲缘关系相较于此前中国境内蝙蝠源类SARS冠状病毒的报道结果更为疏远。值得注意的是，通过致病性实验发现，该病毒可在乳鼠体内增殖并致病；进一步的电镜观察结果显示，乳鼠脑组织中可观察到类病毒颗粒。综上，本研究不仅深化了对蝙蝠携带的类SARS冠状病毒遗传多样性的认知，同时也为以乳鼠作为动物模型，探究类SARS冠状病毒跨物种传播的可能性提供了全新的研究视角。