title: Interaction of influenza A virus matrix protein with RACK1 is required for virus release.
abstract: The mechanism of budding of influenza A virus revealed important deviation from the consensus mechanism of budding of retroviruses and of a growing number of negative-strand RNA viruses. This study is focused on the role of the influenza A virus matrix protein M1 in virus release. We found that a mutation of the proline residue at position 16 of the matrix protein induces inhibition of virus detachment from cells. Depletion of the M1-binding protein RACK1 also impairs virus release and RACK1 binding requires the proline residue at position 16 of M1. The impaired M1-RACK1 interaction does not affect the plasma membrane binding of M1; in contrast, RACK1 is recruited to detergent-resistant membranes in a M1-proline-16-dependent manner. The proline-16 mutation in M1 and depletion of RACK1 impairs the pinching-off of the budding virus particles. These findings reveal the active role of the viral matrix protein in the release of influenza A virus particles that involves a cross-talk with a RACK1-mediated pathway.
authors.affiliation: Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), University of Münster, 48149 Münster, Germany.
authors.forename: Dimiter
authors.initials: D
authors.lastname: Demirov
authors.forename: Gülsah
authors.initials: G
authors.lastname: Gabriel
authors.forename: Carola
authors.initials: C
authors.lastname: Schneider
authors.forename: Heinrich
authors.initials: H
authors.lastname: Hohenberg
authors.forename: Stephan
authors.initials: S
authors.lastname: Ludwig
mesh_terms: D002460:Cell Line; D019204:GTP-Binding Proteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000502:physiology*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000378:metabolism*; D011392:Proline / Q000235:genetics / Q000378:metabolism; D025941:Protein Interaction Mapping; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D057074:Virus Release
chemical_list: C488936:M1 protein, Influenza A virus; D050505:Mutant Proteins; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D014763:Viral Matrix Proteins; D011392:Proline; D019204:GTP-Binding Proteins