title: F-actin modulates measles virus cell-cell fusion and assembly by altering the interaction between the matrix protein and the cytoplasmic tail of hemagglutinin.
abstract: Actin filament (F-actin) is believed to be involved in measles virus (MV) assembly as a cellular factor, but the precise roles remain unknown. Here we show that Phe at position 50 of the MV matrix (M) protein is important for its association with F-actin, through which the function of the M protein is regulated. In plasmid-expressed or MV-infected cells, a coimmunoprecipitation study revealed that the wild-type M (M-WT) protein associated strongly with F-actin but only weakly with the cytoplasmic tail of the hemagglutinin (H) protein. Since the F50P mutation allowed the M protein the enhanced interaction with the H protein in return for the sharply declined association with F-actin, the mutant M (M-F50P) protein strongly inhibited MV cell-cell fusion and promoted the uptake of the H protein into virus particles. The abundantly incorporated H protein resulted in the increase in infectivity of the F50P virus, although the virus contained a level of genome RNA equal to that of the WT virus. When the structure of F-actin was disrupted with cytochalasin D, the M-WT protein liberated from F-actin interacted with the H protein as tightly as the M-F50P protein, suppressing cell-cell fusion and promoting virus assembly comparably efficiently as the M-F50P protein. The cell-cell fusion activity of the WT virus appeared to be upheld by F-actin, which prevents the M protein interaction with the H protein. Our results indicate that F-actin in association with the M protein alters the interaction between the M and H proteins, thereby modulating MV cell-cell fusion and assembly.
authors.affiliation: Department of Microbiology, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, Shiga, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakimoto
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Shimodo
authors.forename: Yuto
authors.initials: Y
authors.lastname: Satoh
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Bin
authors.initials: B
authors.lastname: Gotoh
authors.forename: Masae
authors.initials: M
authors.lastname: Itoh
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D006389:Hemagglutinins, Viral / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D047468:Immunoprecipitation; D008459:Measles virus / Q000502:physiology*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D011485:Protein Binding; D025941:Protein Interaction Mapping; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly
chemical_list: D000199:Actins; D006389:Hemagglutinins, Viral; D050505:Mutant Proteins; D014763:Viral Matrix Proteins; C032397:hemagglutinin protein G, measles virus