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.