Host-Viral Infection Maps Reveal Signatures of Severe COVID-19 Patients

Host-Viral Infection Maps Reveal Signatures of Severe COVID-19 Patients
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宿主病毒感染图谱揭示了重症 COVID-19 患者的特征

DOI:
10.1016/j.cell.2020.05.006
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发表时间:
2020-06-25
期刊:
影响因子:
64.5
通讯作者:
Amit, Ido
Amit, Ido
中科院分区:
生物学1区
文献类型:
--
作者:
Bost, Pierre;Giladi, Amir;Amit, Ido

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正如当前的新冠肺炎大流行所强调的那样,病毒是对全球健康的持续威胁。目前,缺乏人类宿主如何与包括SARS-CoV-2病毒在内的病毒相互作用的数据,限制了有效的治疗干预。我们引入了病毒跟踪,这是一种计算方法,它全局扫描未映射的单细胞RNA测序(scRNA-seq)数据以发现病毒RNA的存在,从而能够对感染细胞和旁观者细胞进行转录细胞分类。我们证明了病毒跟踪在无监督方式下系统检测包括乙肝病毒在内的多种感染模式的病毒的敏感性和特异性。将病毒跟踪应用于重症和轻型新冠肺炎患者的支气管肺泡灌洗样本,显示与轻型患者相比,重型患者的病毒对免疫系统的影响更大。病毒跟踪检测到一种意想不到的人类偏肺病毒的混合感染,主要存在于干扰I型干扰素信号的单核细胞中。病毒跟踪为剖析病毒感染和病理机制提供了一种强大的技术。
Viruses are a constant threat to global health as highlighted by the current COVID-19 pandemic. Currently, lack of data underlying how the human host interacts with viruses, including the SARS-CoV-2 virus, limits effective therapeutic intervention. We introduce Viral-Track, a computational method that globally scans unmapped single-cell RNA sequencing (scRNA-seq) data for the presence of viral RNA, enabling transcriptional cell sorting of infected versus bystander cells. We demonstrate the sensitivity and specificity of Viral-Track to systematically detect viruses from multiple models of infection, including hepatitis B virus, in an unsupervised manner Applying Viral-Track to bronchoalveloar-lavage samples from severe and mild COVID-19 patients reveals a dramatic impact of the virus on the immune system of severe patients compared to mild cases. Viral-Track detects an unexpected co-infection of the human metapneumovirus, present mainly in monocytes perturbed in type-I interferon (IFN)-signaling. Viral-Track provides a robust technology for dissecting the mechanisms of viral-infection and pathology.