Endosomal fusion of pH-dependent enveloped viruses requires ion channel TRPM7.
TRPM Cation Channels
/ metabolism
Endosomes
/ metabolism
Hydrogen-Ion Concentration
Humans
Virus Internalization
Animals
HEK293 Cells
SARS-CoV-2
/ physiology
Protein Serine-Threonine Kinases
/ metabolism
Ebolavirus
/ physiology
Lymphocytic choriomeningitis virus
/ physiology
Chlorocebus aethiops
Viral Envelope
/ metabolism
Lassa virus
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 Oct 2024
01 Oct 2024
Historique:
received:
16
04
2024
accepted:
19
09
2024
medline:
2
10
2024
pubmed:
2
10
2024
entrez:
1
10
2024
Statut:
epublish
Résumé
The majority of viruses classified as pandemic threats are enveloped viruses which enter the cell through receptor-mediated endocytosis and take advantage of endosomal acidification to activate their fusion machinery. Here we report that the endosomal fusion of low pH-requiring viruses is highly dependent on TRPM7, a widely expressed TRP channel that is located on the plasma membrane and in intracellular vesicles. Using several viral infection systems expressing the envelope glycoproteins of various viruses, we find that loss of TRPM7 protects cells from infection by Lassa, LCMV, Ebola, Influenza, MERS, SARS-CoV-1, and SARS-CoV-2. TRPM7 ion channel activity is intrinsically necessary to acidify virus-laden endosomes but is expendable for several other endosomal acidification pathways. We propose a model wherein TRPM7 ion channel activity provides a countercurrent of cations from endosomal lumen to cytosol necessary to sustain the pumping of protons into these virus-laden endosomes. This study demonstrates the possibility of developing a broad-spectrum, TRPM7-targeting antiviral drug to subvert the endosomal fusion of low pH-dependent enveloped viruses.
Identifiants
pubmed: 39353909
doi: 10.1038/s41467-024-52773-w
pii: 10.1038/s41467-024-52773-w
doi:
Substances chimiques
TRPM Cation Channels
0
TRPM7 protein, human
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8479Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : AI155808
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : AI163019
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : AI147394
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : AI112844
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : AI154598
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : AI030557
Organisme : NIAID NIH HHS
ID : T32 AI007245
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : GM108989
Organisme : NIGMS NIH HHS
ID : T32 GM007267
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007055
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : HL170961
Informations de copyright
© 2024. The Author(s).
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