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SARS-CoV-2 requires acidic pH to infect cells.
Kreutzberger, Alex J B; Sanyal, Anwesha; Saminathan, Anand; Bloyet, Louis-Marie; Stumpf, Spencer; Liu, Zhuoming; Ojha, Ravi; Patjas, Markku T; Geneid, Ahmed; Scanavachi, Gustavo; Doyle, Catherine A; Somerville, Elliott; Correia, Ricardo Bango Da Cunha; Di Caprio, Giuseppe; Toppila-Salmi, Sanna; Mäkitie, Antti; Kiessling, Volker; Vapalahti, Olli; Whelan, Sean P J; Balistreri, Giuseppe; Kirchhausen, Tom.
  • Kreutzberger AJB; Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
  • Sanyal A; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
  • Saminathan A; Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
  • Bloyet LM; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
  • Stumpf S; Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
  • Liu Z; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
  • Ojha R; Department of Molecular Microbiology, Washington University in Saint Louis, St. Louis, MO 63110.
  • Patjas MT; Department of Molecular Microbiology, Washington University in Saint Louis, St. Louis, MO 63110.
  • Geneid A; Department of Molecular Microbiology, Washington University in Saint Louis, St. Louis, MO 63110.
  • Scanavachi G; Department of Virology, Faculty of Medicine, University of Helsinki, Helsinki, 00290 Finland.
  • Doyle CA; Department of Otorhinolaryngology and Phoniatrics - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, 00290 Finland.
  • Somerville E; Department of Otorhinolaryngology and Phoniatrics - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, 00290 Finland.
  • Correia RBDC; Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
  • Di Caprio G; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
  • Toppila-Salmi S; Department of Pharmacology, University of Virginia, Charlottesville, VA 22903.
  • Mäkitie A; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
  • Kiessling V; Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
  • Vapalahti O; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
  • Whelan SPJ; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
  • Balistreri G; Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
  • Kirchhausen T; Department of Allergy, University of Helsinki and Helsinki University Hospital, Helsinki, 00290 Finland.
Proc Natl Acad Sci U S A ; 119(38): e2209514119, 2022 09 20.
Article in English | MEDLINE | ID: covidwho-2017036
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry starts with membrane attachment and ends with spike (S) protein-catalyzed membrane fusion depending on two cleavage steps, namely, one usually by furin in producing cells and the second by TMPRSS2 on target cells. Endosomal cathepsins can carry out both. Using real-time three-dimensional single-virion tracking, we show that fusion and genome penetration require virion exposure to an acidic milieu of pH 6.2 to 6.8, even when furin and TMPRSS2 cleavages have occurred. We detect the sequential steps of S1-fragment dissociation, fusion, and content release from the cell surface in TMPRRS2-overexpressing cells only when exposed to acidic pH. We define a key role of an acidic environment for successful infection, found in endosomal compartments and at the surface of TMPRSS2-expressing cells in the acidic milieu of the nasal cavity.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases / Virus Internalization / SARS-CoV-2 / COVID-19 / Nasal Cavity Limits: Humans Language: English Journal: Proc Natl Acad Sci U S A Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases / Virus Internalization / SARS-CoV-2 / COVID-19 / Nasal Cavity Limits: Humans Language: English Journal: Proc Natl Acad Sci U S A Year: 2022 Document Type: Article