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《Science，11月24日，Kallikrein 13 serves as a priming protease during infection by the human coronavirus HKU1》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2020-12-22

  • Kallikrein 13 serves as a priming protease during infection by the human coronavirus HKU1

    View ORCID ProfileAleksandra Milewska1,2, View ORCID ProfileKatherine Falkowski2, View ORCID ProfileMagdalena Kulczycka3, Ewa Bielecka3, View ORCID ProfileAntonina Naskalska1,...

    Science Signaling 24 Nov 2020:

    Vol. 13, Issue 659, eaba9902

    DOI: 10.1126/scisignal.aba9902

    Abstract

    Human coronavirus HKU1 (HCoV-HKU1) is associated with respiratory disease and is prevalent worldwide, but an in vitro model for viral replication is lacking. An interaction between the coronaviral spike (S) protein and its receptor is the primary determinant of tissue and host specificity; however, viral entry is a complex process requiring the concerted action of multiple cellular elements. Here, we found that the protease kallikrein 13 (KLK13) was required for the infection of human respiratory epithelial cells and was sufficient to mediate the entry of HCoV-HKU1 into nonpermissive RD cells. We also demonstrated the cleavage of the HCoV-HKU1 S protein by KLK13 in the S1/S2 region, suggesting that KLK13 is the priming enzyme for this virus. Together, these data suggest that protease distribution and specificity determine the tissue and cell specificity of the virus and may also regulate interspecies transmission.

  • 原文来源：https://stke.sciencemag.org/content/13/659/eaba9902
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相关报告

  • 《11月24日_KLK13是HCoV-HKU1感染过程的启动蛋白酶》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-12-22
    • Science Signaling期刊于11月24日发表了波兰雅盖隆大学的文章“Kallikrein 13 serves as a priming protease during infection by the human coronavirus HKU1”，文章称，在人类冠状病毒HKU1（HCoV-HKU1）感染过程中，激肽释放酶13（KLK13）是一种启动蛋白酶。 文章称，HCoV-HKU1与呼吸系统疾病有关，在世界范围内流行，与SARS-CoV-2不同，HCoV-HKU1通常会引起相对轻度的呼吸道感染。然而，它与SARS-CoV-2共享使用其表面刺突（S）蛋白进入靶细胞的机制。由于尚不知道HCoV-HKU1的宿主受体，因此难以在细胞培养系统中研究该病毒。冠状病毒刺突蛋白与其受体之间的相互作用是决定组织和宿主特异性的主要因素；然而，病毒进入宿主细胞是一个复杂的过程，需要多种细胞元素的协同作用。研究人员发现敲除人气道上皮细胞中的KLK13可以阻止其被HCoV-HKU1感染，KLK13在非允许细胞中的过表达使它们能够被病毒感染。KLK13是感染人类呼吸上皮细胞所必需的。该研究还证实了KLK13在S1/S2区域裂解HCoV-HKU1 S蛋白，证实了KLK13是病毒进入宿主细胞的启动酶，可能有助于建立细胞系，进一步研究病毒发病机制。这些数据表明，蛋白酶的分布和特异性决定了病毒的组织和细胞特异性，也可能调节物种间的传播。 来源：https://stke.sciencemag.org/content/13/659/eaba9902
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  • 《BioRxiv，3月2日，Kallikrein 13: a new player in coronaviral infections.》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-03-03
    • Kallikrein 13: a new player in coronaviral infections. Aleksandra Milewska, Katherine Falkowski, Magdalena Kalinska, Ewa Bielecka, Antonina Naskalska, Pawel Mak, Adam Lesner, Marek Ochman, Maciej Urlik, Jan Potempa, Tomasz Kantyka, Krzysztof Pyrc doi: https://doi.org/10.1101/2020.03.01.971499 Abstract Human coronavirus HKU1 (HCoV-HKU1) is associated with respiratory disease and is prevalent worldwide, but in vitro model for virus replication is lacking. Interaction between the coronaviral spike (S) protein and its receptor is the major determinant of virus tissue and host specificity, but virus entry is a complex process requiring a concerted action of multiple cellular elements. Here, we show that KLK13 is required for the infection of the human respiratory epithelium and is sufficient to mediate the entry of HCoV-HKU1 to non-permissive RD cells. We also demonstrated HCoV-HKU1 S protein cleavage by KLK13 in the S1/S2 region, proving that KLK13 is the priming enzyme for this virus. Summarizing, we show for the first time that protease distribution and specificity predetermines the tissue and cell specificity of the virus and may also regulate interspecies transmission. It is of importance that presented data may be relevant for the emerging coronaviruses, including SARS-CoV-2, and may help to understand the differences in their zoonotic potential. *注，本文为预印本论文手稿，是未经同行评审的初步报告，其观点仅供科研同行交流，并不是结论性内容，请使用者谨慎使用.
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