Endosomal fusion of pH-dependent enveloped viruses requires ion channel TRPM7

Area of Science:

• Virology
• Cell Biology
• Ion Channel Physiology

Background:

• Pandemic threats often involve enveloped viruses that utilize endosomal acidification for cell entry.
• Receptor-mediated endocytosis and subsequent endosomal acidification are critical steps for many viral infections.

Purpose of the Study:

• To investigate the role of the Transient Receptor Potential Melastatin 7 (TRPM7) channel in the endosomal fusion of enveloped viruses.
• To determine if TRPM7 is a potential target for broad-spectrum antiviral therapies.

Main Methods:

• Utilized multiple viral infection systems expressing envelope glycoproteins from various viruses.
• Assessed cellular protection from viral infection in the presence and absence of TRPM7 function.
• Investigated the necessity of TRPM7 ion channel activity for endosomal acidification.

Main Results:

• Loss of TRPM7 conferred protection against infection by Lassa, LCMV, Ebola, Influenza, MERS, SARS-CoV-1, and SARS-CoV-2.
• TRPM7 ion channel activity is crucial for acidifying virus-laden endosomes.
• TRPM7's role in acidification is specific to viral endosomes, not general endosomal pathways.

Conclusions:

• TRPM7 ion channel activity is indispensable for the endosomal fusion of low pH-dependent enveloped viruses.
• A model is proposed where TRPM7 facilitates proton pumping into endosomes via cation countercurrent.
• Targeting TRPM7 presents a promising strategy for developing broad-spectrum antiviral drugs against enveloped viruses.