SARS-CoV-2 requires acidic pH to infect cells.
3D imaging
SARS-CoV-2
infection route
live-cell imaging
virus entry
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
20 09 2022
20 09 2022
Historique:
entrez:
1
9
2022
pubmed:
2
9
2022
medline:
9
9
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36048924
doi: 10.1073/pnas.2209514119
pmc: PMC9499588
doi:
Substances chimiques
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Serine Endopeptidases
EC 3.4.21.-
TMPRSS2 protein, human
EC 3.4.21.-
Furin
EC 3.4.21.75
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2209514119Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM130386
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI163019
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007245
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI030557
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI030557
Pays : United States
Commentaires et corrections
Type : UpdateOf
Références
Science. 2020 Mar 13;367(6483):1260-1263
pubmed: 32075877
Nature. 2021 Mar;591(7849):293-299
pubmed: 33494095
Nat Commun. 2020 Sep 11;11(1):4541
pubmed: 32917884
Nat Commun. 2020 Oct 12;11(1):5139
pubmed: 33046696
Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5871-6
pubmed: 19321428
Science. 2020 Mar 27;367(6485):1444-1448
pubmed: 32132184
Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15382-7
pubmed: 18829437
Virology. 2011 May 10;413(2):265-74
pubmed: 21435673
PLoS Pathog. 2010 Sep 30;6(9):e1001127
pubmed: 20941355
Mol Biol Cell. 2014 Nov 5;25(22):3630-42
pubmed: 25232006
Dev Cell. 2006 Jun;10(6):839-50
pubmed: 16740485
Clin Otolaryngol Allied Sci. 1999 Feb;24(1):67-8
pubmed: 10196653
J Cell Biol. 1994 Nov;127(4):915-34
pubmed: 7962076
Cell. 2012 Aug 3;150(3):495-507
pubmed: 22863004
Sci Immunol. 2020 May 13;5(47):
pubmed: 32404436
Elife. 2013 Feb 19;2:e00333
pubmed: 23550179
Science. 2014 Oct 24;346(6208):1257998
pubmed: 25342811
Nature. 2022 Mar;603(7902):706-714
pubmed: 35104837
Viruses. 2020 Oct 16;12(10):
pubmed: 33081421
Nat Rev Mol Cell Biol. 2012 Jan 11;13(2):75-88
pubmed: 22233676
Dev Cell. 2021 Jun 21;56(12):1786-1803.e9
pubmed: 34129835
Emerg Microbes Infect. 2022 Dec;11(1):277-283
pubmed: 34951565
J Virol. 2011 May;85(9):4122-34
pubmed: 21325420
Cold Spring Harb Perspect Biol. 2014 May 22;6(10):a016857
pubmed: 24851870
Mol Biol Cell. 2016 Nov 7;27(22):3418-3435
pubmed: 27535432
Cell Host Microbe. 2020 Sep 9;28(3):475-485.e5
pubmed: 32735849
Proc Natl Acad Sci U S A. 2017 Jan 3;114(1):E28-E36
pubmed: 27974607
Science. 2021 Mar 26;371(6536):1379-1382
pubmed: 33597220
Proc Natl Acad Sci U S A. 2020 May 26;117(21):11727-11734
pubmed: 32376634
Nat Microbiol. 2021 Jul;6(7):899-909
pubmed: 33907312
Proc Natl Acad Sci U S A. 2020 Aug 25;117(34):20803-20813
pubmed: 32764148
PLoS Pathog. 2014 Sep 11;10(9):e1004355
pubmed: 25211455
Am J Otolaryngol. 2013 Sep-Oct;34(5):505-7
pubmed: 23731849
J Virol. 2021 Oct 13;95(21):e0097521
pubmed: 34406858
Nat Commun. 2020 Mar 27;11(1):1620
pubmed: 32221306
Nat Rev Mol Cell Biol. 2022 Jan;23(1):3-20
pubmed: 34611326
J Gen Microbiol. 1966 Sep;44(3):359-71
pubmed: 4291279
Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):15214-9
pubmed: 25288733
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
J Clin Invest. 1969 Nov;48(11):1983-96
pubmed: 4898722
Proc Natl Acad Sci U S A. 2020 Dec 15;117(50):32105-32113
pubmed: 33239446
Elife. 2014 Dec 05;3:e04389
pubmed: 25479384
Life Sci Alliance. 2020 Jul 23;3(9):
pubmed: 32703818
Cell Res. 2022 Mar;32(3):319-321
pubmed: 35064226