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Endosomal fusion of pH-dependent enveloped viruses requires ion channel TRPM7.
- Source :
-
Nature communications [Nat Commun] 2024 Oct 01; Vol. 15 (1), pp. 8479. Date of Electronic Publication: 2024 Oct 01. - Publication Year :
- 2024
-
Abstract
- 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.<br /> (© 2024. The Author(s).)
- Subjects :
- Hydrogen-Ion Concentration
Humans
Animals
HEK293 Cells
SARS-CoV-2 physiology
SARS-CoV-2 metabolism
Protein Serine-Threonine Kinases metabolism
Protein Serine-Threonine Kinases genetics
Ebolavirus physiology
Ebolavirus metabolism
Lymphocytic choriomeningitis virus physiology
Chlorocebus aethiops
Viral Envelope metabolism
Lassa virus metabolism
Lassa virus physiology
TRPM Cation Channels metabolism
TRPM Cation Channels genetics
Endosomes metabolism
Endosomes virology
Virus Internalization
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 39353909
- Full Text :
- https://doi.org/10.1038/s41467-024-52773-w