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Reports

Toxicity of Influenza A Virus Matrix Protein 2 for Mammalian Cells is Associated with its Intrinsic Proton-Channeling Activity

Petr O. Ilyinskii, Vladimir L. Gabai, Shamil R. Sunyaev, Galini Thoidis and Alexander M. Shneider

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Molecules of influenza matrix protein 2 (M2) are organized in tetramers that constitute a well-conserved virion component and also form proton channels in the plasma membrane of infected cells. In this report we demonstrate that influenza M2 protein is cytopathic in vitro for mammalian cells. An M2 point-mutant (M2pm) protein was constructed that contained amino acid changes designed to block the proton channel via introduction of large hydrophobic residues. This mutant was significantly less toxic upon transient transfection in vitro than the wild-type M2 (M2wt). To assess the possible correlation between M2 cytotoxicity and its proton channel activity, we monitored changes in mitochondria membrane potential induced by M2wt and M2pm. M2wt rapidly decreased mitochondria membrane potential reflecting the transmembrane proton gradient, while M2pm was markedly less efficient. Thus, M2 is cytotoxic for mammalian cells, likely via its proton channel activity and may therefore contribute to influenza pathogenesis through this previously unknown mechanism.

Authors

Petr O. Ilyinskii

Cure Lab, Inc.; Canton, Massachusetts

Vladimir L. Gabai

Boston University School of Medicine; Boston, Massachusetts

Shamil R. Sunyaev

Harvard Medical School; Boston, Massachusetts

Galini Thoidis

Cure Lab, Inc.; Canton, Massachusetts

Alexander M. Shneider

Cure Lab, Inc.; Canton, Massachusetts

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.