登录
 机构网站
  1. 首页
  2. 情报产品
  3. 快讯详情

《Nature，8月6日，Genetic variability in the expression of the SARS-CoV-2 host cell entry factors across populations》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2020-08-18

  • Genetic variability in the expression of the SARS-CoV-2 host cell entry factors across populations
    Lourdes Ortiz-Fernández & Amr H. Sawalha
    Genes & Immunity (2020)

    Abstract
    The entry of SARS-CoV-2 into host cells is dependent upon angiotensin-converting enzyme 2 (ACE2), which serves as a functional attachment receptor for the viral spike glycoprotein, and the serine protease TMPRSS2 which allows fusion of the viral and host cell membranes. We devised a quantitative measure to estimate genetic determinants of ACE2 and TMPRSS2 expression and applied this measure to >2500 individuals. Our data show significant variability in genetic determinants of ACE2 and TMPRSS2 expression among individuals and between populations, and indicate a genetic predisposition for lower expression levels of both key viral entry genes in African populations. These data suggest that host genetics related to viral entry mechanisms might influence interindividual variability in disease susceptibility and severity of COVID-19.

  • 原文来源：https://www.nature.com/articles/s41435-020-0107-7
97浏览量
原文链接
相关报告

  • 《Cell，12月8日，Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-12-23
    • Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses Ruofan Wang 13 Camille R. Simoneau 13 Jessie Kulsuptrakul Nevan J. Krogan Melanie Ott Andreas S. Puschnik 14 Show all authors Show footnotes Published:December 08, 2020DOI:https://doi.org/10.1016/j.cell.2020.12.004 Summary The Coronaviridae are a family of viruses that cause disease in humans ranging from mild respiratory infection to potentially lethal acute respiratory distress syndrome. Finding host factors common to multiple coronaviruses could facilitate the development of therapies to combat current and future coronavirus pandemics. Here, we conducted genome-wide CRISPR screens in cells infected by SARS-CoV-2 as well as two seasonally circulating common cold coronaviruses, OC43 and 229E. This approach correctly identified the distinct viral entry factors ACE2 (for SARS-CoV-2), aminopeptidase N (for 229E), and glycosaminoglycans (for OC43). Additionally, we identified phosphatidylinositol phosphate biosynthesis and cholesterol homeostasis as critical host pathways supporting infection by all three coronaviruses. By contrast, the lysosomal protein TMEM106B appeared unique to SARS-CoV-2 infection. Pharmacological inhibition of phosphatidylinositol kinases and cholesterol homeostasis reduced replication of all three coronaviruses. These findings offer important insights for the understanding of the coronavirus life cycle and the development of host-directed therapies.
    49浏览量
    原文链接

  • 《Cell，10月20日，Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-11-16
    • Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection Jin Wei Mia Madel Alfajaro Peter C. DeWeirdt Qin Yan John G. Doench Craig B. Wilen 18 Show all authors Show footnotes Published:October 20, 2020DOI:https://doi.org/10.1016/j.cell.2020.10.028 Summary Identification of host genes essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may reveal novel therapeutic targets and inform our understanding of coronavirus disease 2019 (COVID-19) pathogenesis. Here we performed genome-wide CRISPR screens in Vero-E6 cells with SARS-CoV-2, Middle East respiratory syndrome CoV (MERS-CoV), bat CoV HKU5 expressing the SARS-CoV-1 spike, and vesicular stomatitis virus (VSV) expressing the SARS-CoV-2 spike. We identified known SARS-CoV-2 host factors, including the receptor ACE2 and protease Cathepsin L. We additionally discovered pro-viral genes and pathways, including HMGB1 and the SWI/SNF chromatin remodeling complex, that are SARS lineage and pan-coronavirus specific, respectively. We show that HMGB1 regulates ACE2 expression and is critical for entry of SARS-CoV-2, SARS-CoV-1, and NL63. We also show that small-molecule antagonists of identified gene products inhibited SARS-CoV-2 infection in monkey and human cells, demonstrating the conserved role of these genetic hits across species. This identifies potential therapeutic targets for SARS-CoV-2 and reveals SARS lineage-specific and pan-CoV host factors that regulate susceptibility to highly pathogenic CoVs.
    92浏览量
    原文链接