title: Toxicity of influenza A virus matrix protein 2 for mammalian cells is associated with its intrinsic proton-channeling activity.
abstract: 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: Cure Lab, Inc., Canton, Massachusetts 02021, USA. ilyinskii@curelab.com
authors: Petr O
authors: PO
authors: Ilyinskii
authors: Vladimir L
authors: VL
authors: Gabai
authors: Shamil R
authors: SR
authors: Sunyaev
authors: Galini
authors: G
authors: Thoidis
authors: Alexander M
authors: AM
authors: Shneider
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014162:Transfection; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D014763:Viral Matrix Proteins