Systematic analysis of SARS-CoV-2 infection of an ACE2-negative human airway cell.
Amino Acid Substitution
Angiotensin-Converting Enzyme 2
Animals
Antibodies, Monoclonal
/ immunology
Antibodies, Viral
/ immunology
COVID-19
/ immunology
Cell Cycle
Cell Line, Tumor
Chlorocebus aethiops
Gene Expression Profiling
Heparitin Sulfate
/ metabolism
Humans
Interferon Type I
/ metabolism
Interferon-Induced Helicase, IFIH1
/ metabolism
Models, Biological
Protein Binding
Protein Domains
Proteomics
Receptors, Virus
/ metabolism
SARS-CoV-2
Serine Endopeptidases
/ metabolism
Signal Transduction
Spike Glycoprotein, Coronavirus
/ genetics
Vero Cells
Virus Internalization
Virus Replication
ACE2-independent
COVID-19
RIG-I-like receptors
SARS-CoV-2
clathrin-mediated endocytosis
heparan sulfate
proteomics
spike variants
type I interferon
virus-host interactions
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
13 07 2021
13 07 2021
Historique:
received:
04
02
2021
revised:
25
05
2021
accepted:
17
06
2021
pubmed:
3
7
2021
medline:
27
7
2021
entrez:
2
7
2021
Statut:
ppublish
Résumé
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) variants govern transmissibility, responsiveness to vaccination, and disease severity. In a screen for new models of SARS-CoV-2 infection, we identify human H522 lung adenocarcinoma cells as naturally permissive to SARS-CoV-2 infection despite complete absence of angiotensin-converting enzyme 2 (ACE2) expression. Remarkably, H522 infection requires the E484D S variant; viruses expressing wild-type S are not infectious. Anti-S monoclonal antibodies differentially neutralize SARS-CoV-2 E484D S in H522 cells as compared to ACE2-expressing cells. Sera from vaccinated individuals block this alternative entry mechanism, whereas convalescent sera are less effective. Although the H522 receptor remains unknown, depletion of surface heparan sulfates block H522 infection. Temporally resolved transcriptomic and proteomic profiling reveal alterations in cell cycle and the antiviral host cell response, including MDA5-dependent activation of type I interferon signaling. These findings establish an alternative SARS-CoV-2 host cell receptor for the E484D SARS-CoV-2 variant, which may impact tropism of SARS-CoV-2 and consequently human disease pathogenesis.
Identifiants
pubmed: 34214467
pii: S2211-1247(21)00762-2
doi: 10.1016/j.celrep.2021.109364
pmc: PMC8220945
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Viral
0
Interferon Type I
0
Receptors, Virus
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Heparitin Sulfate
9050-30-0
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Serine Endopeptidases
EC 3.4.21.-
TMPRSS2 protein, human
EC 3.4.21.-
IFIH1 protein, human
EC 3.6.1.-
Interferon-Induced Helicase, IFIH1
EC 3.6.4.13
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
109364Subventions
Organisme : NIAID NIH HHS
ID : R01 AI157155
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009547
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007106
Pays : United States
Organisme : NIDCR NIH HHS
ID : K08 DE029241
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI059371
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL150223
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI059371
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93019C00074
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA216051
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests S.P.J.W., P.W.R., and Washington University have filed a patent application for uses of VSV-SARS-CoV-2. S.P.J.W. has received unrelated funding support in sponsored research agreements with Vir Biotechnology, Abbvie, and SAB therapeutics. M.S.D. is a consultant for Inbios, Vir Biotechnology, Fortress Biotech, and Carnival Corporation, and is on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology, Kaleido, and Emergent BioSolutions. J.E.C. has served as a consultant for Luna Biologics, is a member of the Scientific Advisory Boards of Meissa Vaccines, and is Founder of IDBiologics. The Crowe laboratory has received sponsored research agreements from Takeda, AstraZeneca, and IDBiologics. Vanderbilt University has applied for patents related to antibodies described in this paper. The remaining authors declare no competing interests.
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