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The SARS-CoV-2 and other human coronavirus spike proteins are fine-tuned towards temperature and proteases of the human airways.
Laporte, Manon; Raeymaekers, Valerie; Van Berwaer, Ria; Vandeput, Julie; Marchand-Casas, Isabel; Thibaut, Hendrik-Jan; Van Looveren, Dominique; Martens, Katleen; Hoffmann, Markus; Maes, Piet; Pöhlmann, Stefan; Naesens, Lieve; Stevaert, Annelies.
  • Laporte M; KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Leuven, Belgium.
  • Raeymaekers V; KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Leuven, Belgium.
  • Van Berwaer R; KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Leuven, Belgium.
  • Vandeput J; KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Leuven, Belgium.
  • Marchand-Casas I; KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Leuven, Belgium.
  • Thibaut HJ; KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Leuven, Belgium.
  • Van Looveren D; KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Translational Platform Virology and Chemotherapy, Rega Institute, Leuven, Belgium.
  • Martens K; KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Leuven, Belgium.
  • Hoffmann M; KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Translational Platform Virology and Chemotherapy, Rega Institute, Leuven, Belgium.
  • Maes P; KU Leuven, Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Unit, Leuven, Belgium.
  • Pöhlmann S; German Primate Center-Leibniz Institute for Primate Research, Infection Biology Unit, Göttingen, Germany.
  • Naesens L; University Göttingen, Faculty of Biology and Psychology, Göttingen, Germany.
  • Stevaert A; KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, Leuven, Belgium.
PLoS Pathog ; 17(4): e1009500, 2021 04.
Article in English | MEDLINE | ID: covidwho-1197396
Semantic information from SemMedBD (by NLM)
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ABSTRACT
The high transmissibility of SARS-CoV-2 is related to abundant replication in the upper airways, which is not observed for the other highly pathogenic coronaviruses SARS-CoV and MERS-CoV. We here reveal features of the coronavirus spike (S) protein, which optimize the virus towards the human respiratory tract. First, the S proteins exhibit an intrinsic temperature preference, corresponding with the temperature of the upper or lower airways. Pseudoviruses bearing the SARS-CoV-2 spike (SARS-2-S) were more infectious when produced at 33°C instead of 37°C, a property shared with the S protein of HCoV-229E, a common cold coronavirus. In contrast, the S proteins of SARS-CoV and MERS-CoV favored 37°C, in accordance with virus preference for the lower airways. Next, SARS-2-S-driven entry was efficiently activated by not only TMPRSS2, but also the TMPRSS13 protease, thus broadening the cell tropism of SARS-CoV-2. Both proteases proved relevant in the context of authentic virus replication. TMPRSS13 appeared an effective spike activator for the virulent coronaviruses but not the low pathogenic HCoV-229E virus. Activation of SARS-2-S by these surface proteases requires processing of the S1/S2 cleavage loop, in which both the furin recognition motif and extended loop length proved critical. Conversely, entry of loop deletion mutants is significantly increased in cathepsin-rich cells. Finally, we demonstrate that the D614G mutation increases SARS-CoV-2 stability, particularly at 37°C, and, enhances its use of the cathepsin L pathway. This indicates a link between S protein stability and usage of this alternative route for virus entry. Since these spike properties may promote virus spread, they potentially explain why the spike-G614 variant has replaced the early D614 variant to become globally predominant. Collectively, our findings reveal adaptive mechanisms whereby the coronavirus spike protein is adjusted to match the temperature and protease conditions of the airways, to enhance virus transmission and pathology.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory System / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Topics: Variants Limits: Humans Language: English Journal: PLoS Pathog Year: 2021 Document Type: Article Affiliation country: Journal.ppat.1009500

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory System / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Topics: Variants Limits: Humans Language: English Journal: PLoS Pathog Year: 2021 Document Type: Article Affiliation country: Journal.ppat.1009500