Evidence for an Ancestral Association of Human Coronavirus 229E with Bats
Evidence for an Ancestral Association of Human Coronavirus 229E with Bats
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DOI：
10.1128/jvi.01755-15
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发表时间：
2015-12-01
影响因子：
5.4
通讯作者：
Drexler, Jan Felix
中科院分区：
文献类型：
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作者：
Corman, Victor Max;Baldwin, Heather J.;Drexler, Jan Felix
我们之前表明，人类冠状病毒229E （HCoV-229E）的近亲存在于非洲蝙蝠中。到目前为止，小样本和有限的基因组特征阻碍了进一步的分析。在这里，我们用逆转录- pcr （RT-PCR）检测了来自加纳11种蝙蝠的2087份粪便标本中hcov - 229e相关病毒。只有海马体蝙蝠检测呈阳性。为了比较蝙蝠病毒和HCoV-229E的遗传多样性，我们测试了10年来在全球取样的历史分离株和诊断标本。蝙蝠病毒在RNA依赖性RNA聚合酶（RdRp）和刺突基因上的多样性是HCoV-229E的5倍和6倍。在系统发育分析中，HCoV-229E株是单系的，没有与动物病毒混合。蝙蝠病毒形成了三个大的分支，它们有亲缘关系，也有远亲关系。最近发现的一种与229e相关的羊驼病毒在系统发育上处于蝙蝠和人类病毒之间的中间位置。根据分类学标准，人类、羊驼和蝙蝠病毒形成单一冠状病毒物种，显示出多次重组事件的证据。与所有蝙蝠病毒相比，HCoV-229E和羊驼病毒在刺突S1区存在主要缺失。对来自229e相关蝙蝠冠状病毒的4个全基因组的分析发现，第8个开放阅读框（ORF8）位于基因组3'端。ORF8也存在于与229e相关的羊驼病毒中。对HCoV-229E序列的再分析显示，在该ORF残体之前有一个保守的转录调控序列，表明它是在人类获得229e相关冠状病毒后丢失的。这些数据表明，与229e相关的冠状病毒在马体类蝙蝠中的进化起源，假设在HCoV-229E建立之前，骆驼类作为中间宿主。重要意义主要人类冠状病毒（hcov）的祖先起源可能与蝙蝠宿主有关。在这里，我们通过分析大量非洲蝙蝠样本并在全基因组水平上表征几种蝙蝠病毒，为海马体蝙蝠中普通感冒病毒HCoV-229E的进化起源提供了确凿的遗传证据。我们的进化分析表明，动物病毒和人类病毒在遗传上密切相关，可以交换遗传物质，形成单一的病毒物种。我们发现，导致HCoV-229E形成的假定宿主开关伴随着主要的基因组变化，包括病毒刺突糖蛋白基因的缺失和开放阅读框的缺失。我们重新分析了先前描述的遗传相关的羊驼病毒，并讨论了骆驼作为蝙蝠和人类病毒之间潜在的中间宿主的作用。HCoV-229E的进化史可能与最近出现的高致病性中东呼吸综合征（MERS）冠状病毒具有重要特征。
We previously showed that close relatives of human coronavirus 229E (HCoV-229E) exist in African bats. The small sample and limited genomic characterizations have prevented further analyses so far. Here, we tested 2,087 fecal specimens from 11 bat species sampled in Ghana for HCoV-229E-related viruses by reverse transcription-PCR (RT-PCR). Only hipposiderid bats tested positive. To compare the genetic diversity of bat viruses and HCoV-229E, we tested historical isolates and diagnostic specimens sampled globally over 10 years. Bat viruses were 5- and 6-fold more diversified than HCoV-229E in the RNA-dependent RNA polymerase (RdRp) and spike genes. In phylogenetic analyses, HCoV-229E strains were monophyletic and not intermixed with animal viruses. Bat viruses formed three large clades in close and more distant sister relationships. A recently described 229E-related alpaca virus occupied an intermediate phylogenetic position between bat and human viruses. According to taxonomic criteria, human, alpaca, and bat viruses form a single CoV species showing evidence for multiple recombination events. HCoV-229E and the alpaca virus showed a major deletion in the spike S1 region compared to all bat viruses. Analyses of four full genomes from 229E-related bat CoVs revealed an eighth open reading frame (ORF8) located at the genomic 3' end. ORF8 also existed in the 229E-related alpaca virus. Reanalysis of HCoV-229E sequences showed a conserved transcription regulatory sequence preceding remnants of this ORF, suggesting its loss after acquisition of a 229E-related CoV by humans. These data suggested an evolutionary origin of 229E-related CoVs in hipposiderid bats, hypothetically with camelids as intermediate hosts preceding the establishment of HCoV-229E.IMPORTANCEThe ancestral origins of major human coronaviruses (HCoVs) likely involve bat hosts. Here, we provide conclusive genetic evidence for an evolutionary origin of the common cold virus HCoV-229E in hipposiderid bats by analyzing a large sample of African bats and characterizing several bat viruses on a full-genome level. Our evolutionary analyses show that animal and human viruses are genetically closely related, can exchange genetic material, and form a single viral species. We show that the putative host switches leading to the formation of HCoV-229E were accompanied by major genomic changes, including deletions in the viral spike glycoprotein gene and loss of an open reading frame. We reanalyze a previously described genetically related alpaca virus and discuss the role of camelids as potential intermediate hosts between bat and human viruses. The evolutionary history of HCoV-229E likely shares important characteristics with that of the recently emerged highly pathogenic Middle East respiratory syndrome (MERS) coronavirus.