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J Virol. 2017 Mar 29. pii: JVI.00267-17. doi: 10.1128/JVI.00267-17. [Epub ahead of print]
Phosphatidylserine Lateral Organization Influences the Interaction of Influenza Matrix Protein 1 with Lipid Membranes.
Bobone S1,2, Hilsch M1, Storm J1, Dunsing V2, Herrmann A1, Chiantia S3.
Author information
Abstract
Influenza A Virus Matrix Protein 1 (M1) is an essential component involved in the structural stability of the virus and in the budding of new virions from infected cells. A deeper understanding of the molecular basis of virion formation and budding process is required in order to devise new therapeutic approaches. We investigated in details the interaction between M1 and phosphatidylserine (PS) (i.e., its main binding target at the plasma membrane (PM)), as well as the distribution of PS itself, both in model membranes and in living cells. To this aim, we used a combination of techniques including FRET, confocal microscopy imaging, Raster Image Correlation Spectroscopy and Number and Brightness (N&B). Our results show that PS can cluster in segregated regions in the plane of the lipid bilayer, both in model bilayers constituted of PS and phosphatidylcholine, as well as in living cells. The viral protein M1 interacts specifically with PS enriched domains and such interaction in turn affects its oligomerization process. Furthermore, M1 can stabilize PS domains, as observed in model membranes. In living cells, the presence of PS clusters is suggested by N&B experiments monitoring the clustering of the PS sensor Lactadherin. Also, co-localization between M1 and a fluorescent PS probe suggest that, in infected cells, the matrix protein can specifically bind to the regions of PM in which PS is clustered.Taken together, our observations provide novel evidence regarding the role of PS rich domains in tuning M1-lipid and M1-M1 interactions at the PM of infected cells.IMPORTANCE Influenza virus particles assemble at the plasma membrane of infected cells. This process is orchestrated by the matrix protein M1 which interacts with membrane lipids, while binding to the other proteins and genetic material of the virus. In spite of its importance, the initial step in virus assembly (i.e. M1-lipid interaction) is still not well understood. In this work, we show that phosphatidylserine can form lipid domains in physical models of the inner leaflet of the PM. Furthermore, the spatial organization of PS in the plane of the bilayer modulates M1-M1 interactions. Finally, we show that PS domains appear to be present in the PM of living cells and that M1 seems to display a high affinity to them.
Copyright ? 2017 American Society for Microbiology.
PMID: 28356535 DOI: 10.1128/JVI.00267-17
Phosphatidylserine Lateral Organization Influences the Interaction of Influenza Matrix Protein 1 with Lipid Membranes.
Bobone S1,2, Hilsch M1, Storm J1, Dunsing V2, Herrmann A1, Chiantia S3.
Author information
Abstract
Influenza A Virus Matrix Protein 1 (M1) is an essential component involved in the structural stability of the virus and in the budding of new virions from infected cells. A deeper understanding of the molecular basis of virion formation and budding process is required in order to devise new therapeutic approaches. We investigated in details the interaction between M1 and phosphatidylserine (PS) (i.e., its main binding target at the plasma membrane (PM)), as well as the distribution of PS itself, both in model membranes and in living cells. To this aim, we used a combination of techniques including FRET, confocal microscopy imaging, Raster Image Correlation Spectroscopy and Number and Brightness (N&B). Our results show that PS can cluster in segregated regions in the plane of the lipid bilayer, both in model bilayers constituted of PS and phosphatidylcholine, as well as in living cells. The viral protein M1 interacts specifically with PS enriched domains and such interaction in turn affects its oligomerization process. Furthermore, M1 can stabilize PS domains, as observed in model membranes. In living cells, the presence of PS clusters is suggested by N&B experiments monitoring the clustering of the PS sensor Lactadherin. Also, co-localization between M1 and a fluorescent PS probe suggest that, in infected cells, the matrix protein can specifically bind to the regions of PM in which PS is clustered.Taken together, our observations provide novel evidence regarding the role of PS rich domains in tuning M1-lipid and M1-M1 interactions at the PM of infected cells.IMPORTANCE Influenza virus particles assemble at the plasma membrane of infected cells. This process is orchestrated by the matrix protein M1 which interacts with membrane lipids, while binding to the other proteins and genetic material of the virus. In spite of its importance, the initial step in virus assembly (i.e. M1-lipid interaction) is still not well understood. In this work, we show that phosphatidylserine can form lipid domains in physical models of the inner leaflet of the PM. Furthermore, the spatial organization of PS in the plane of the bilayer modulates M1-M1 interactions. Finally, we show that PS domains appear to be present in the PM of living cells and that M1 seems to display a high affinity to them.
Copyright ? 2017 American Society for Microbiology.
PMID: 28356535 DOI: 10.1128/JVI.00267-17