Influenza Virus M2 Ion Channel Protein Is Necessary for Filamentous Virion Formation
Jeremy S. Rossman,Xianghong Jing,Xianghong Jing,George P. Leser,Victoria Balannik,Lawrence H. Pinto,Robert A. Lamb +6 more
TLDR
It is found that an amphipathic helix located within the M2 cytoplasmic tail is able to bind cholesterol, and it is speculated that M2 cholesterol binding is essential for both filament formation and the stability of existing viral filaments.Abstract:
Influenza A virus buds from cells as spherical (∼100-nm diameter) and filamentous (∼100 nm × 2 to 20 μm) virions. Previous work has determined that the matrix protein (M1) confers the ability of the virus to form filaments; however, additional work has suggested that the influenza virus M2 integral membrane protein also plays a role in viral filament formation. In examining the role of the M2 protein in filament formation, we observed that the cytoplasmic tail of M2 contains several sites that are essential for filament formation. Additionally, whereas M2 is a nonraft protein, expression of other viral proteins in the context of influenza virus infection leads to the colocalization of M2 with sites of virus budding and lipid raft domains. We found that an amphipathic helix located within the M2 cytoplasmic tail is able to bind cholesterol, and we speculate that M2 cholesterol binding is essential for both filament formation and the stability of existing viral filaments.read more
Citations
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Meta- and Orthogonal Integration of Influenza “OMICs” Data Defines a Role for UBR4 in Virus Budding
Shashank Tripathi,Marie O. Pohl,Yingyao Zhou,Ariel Rodriguez-Frandsen,Guojun Wang,David A. Stein,Hong M. Moulton,Paul DeJesus,Jianwei Che,Lubbertus C. F. Mulder,Emilio Yángüez,Dario Andenmatten,Lars Pache,Balaji Manicassamy,Randy A. Albrecht,Maria G. Gonzalez,Quy T. Nguyen,Abraham L. Brass,Stephen J. Elledge,Stephen J. Elledge,Michael A. White,Sagi Shapira,Nir Hacohen,Alexander Karlas,Thomas F. Meyer,Michael Shales,Andre Gatorano,Jeffrey R. Johnson,Gwen Jang,Tasha L. Johnson,Erik Verschueren,Doug Sanders,Nevan J. Krogan,Megan L. Shaw,Renate König,Renate König,Silke Stertz,Adolfo García-Sastre,Sumit K. Chanda +38 more
TL;DR: A meta-analysis of data from eight published RNAi screens and integrated with three protein interaction datasets revealed a functionally validated biochemical landscape of the influenza-host interface, which illuminates a viral-host network of high-confidence human proteins that are essential for influenza A virus replication.
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Influenza virus assembly and budding.
TL;DR: This review investigates the latest research on influenza virus budding in an attempt to provide a step-by-step analysis of the assembly and budding processes for influenza viruses.
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Influenza Virus M2 Protein Mediates ESCRT-Independent Membrane Scission
Jeremy S. Rossman,Jeremy S. Rossman,Xianghong Jing,George P. Leser,Robert A. Lamb,Robert A. Lamb +5 more
TL;DR: It is shown that M2 localizes to the neck of budding virions and that mutation of the M2 amphipathic helix results in failure of the virus to undergo membrane scission and virion release, suggesting that M1 mediates the final steps of budding for influenza viruses, bypassing the need for host ESCRT proteins.
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M2e-based universal influenza A vaccine.
TL;DR: Experiments in animal models have demonstrated that M2e-based vaccines induce protection against a lethal challenge with various influenza A virus subtypes, and the production and use of an effective M 2e-vaccine could be implemented at any time regardless of seasonality, both in an epidemic as well as in a pandemic preparedness program.
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Identification of a novel splice variant form of the influenza A virus M2 ion channel with an antigenically distinct ectodomain.
Helen M. Wise,Edward C. Hutchinson,Brett W. Jagger,Brett W. Jagger,Amanda D. Stuart,Zi H. Kang,Nicole C. Robb,Louis M. Schwartzman,John C. Kash,Ervin Fodor,Andrew E. Firth,Julia R. Gog,Jeffery K. Taubenberger,Paul Digard +13 more
TL;DR: In identifying a 14th influenza A polypeptide, the data reinforce the unexpectedly high coding capacity of the viral genome and have implications for virus evolution, as well as for understanding the role of M2 in the virus life cycle.
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