Influenza A Virus M1 Protein Non-Specifically Deforms Charged Lipid Membranes and Specifically Interacts with the Raft Boundary

• Published in: Membranes (Basel) Vol. 13; no. 1; p. 76
• Main Authors: Loshkareva, Anna S, Popova, Marina M, Shilova, Liudmila A, Fedorova, Natalia V, Timofeeva, Tatiana A, Galimzyanov, Timur R, Kuzmin, Petr I, Knyazev, Denis G, Batishchev, Oleg V
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.01.2023; MDPI
• Subjects: Biological membranes; Cell membranes; Confocal microscopy; Deformation; Fluorescence; giant unilamellar vesicle (GUV); Helices; hemagglutinin; HIV; Human immunodeficiency virus; Influenza; Influenza A; influenza A virus; Lipid bilayers; Lipid membranes; Lipids; lipoprotein envelope; M1 matrix protein; Matrix protein; Membranes; Microscopy; Phase separation; Plasma; Polypeptides; Progeny; Proteins; viral budding; Virions; Virus-like particles; Viruses; St Louis Missouri; United States > US; fluorescent confocal microscopy; viral budding; lipid raft; hemagglutinin; M1 matrix protein; membrane deformation; giant unilamellar vesicle (GUV); lipoprotein envelope; amphipathic helices; influenza A virus
• ISSN: 2077-0375; 2077-0375
• DOI: 10.3390/membranes13010076

Topological rearrangements of biological membranes, such as fusion and fission, often require a sophisticated interplay between different proteins and cellular membranes. However, in the case of fusion proteins of enveloped viruses, even one molecule can execute membrane restructurings. Growing evidence indicates that matrix proteins of enveloped viruses can solely trigger the membrane bending required for another crucial step in virogenesis, the budding of progeny virions. For the case of the influenza A virus matrix protein M1, different studies report both in favor and against M1 being able to produce virus-like particles without other viral proteins. Here, we investigated the physicochemical mechanisms of M1 membrane activity on giant unilamellar vesicles of different lipid compositions using fluorescent confocal microscopy. We confirmed that M1 predominantly interacts electrostatically with the membrane, and its ability to deform the lipid bilayer is non-specific and typical for membrane-binding proteins and polypeptides. However, in the case of phase-separating membranes, M1 demonstrates a unique ability to induce macro-phase separation, probably due to the high affinity of M1's amphipathic helices to the raft boundary. Thus, we suggest that M1 is tailored to deform charged membranes with a specific activity in the case of phase-separating membranes.