Single-point mutations of the M protein of a measles virus variant obtained  from a patient with subacute sclerosing panencephalitis critically affect  solubility and subcellular localization of the M protein and cell-free virus  production.
Subacute sclerosing panencephalitis (SSPE) is caused by variants of wild-type measles virus (MV). Such MV variants lack almost completely the ability to produce cell-free progeny virus. We recently isolated an MV variant that has only three amino acid mutations (L165P,L250P and Y282H) in the M protein compared with MV field isolates of the same genotype. In the present study, we analyzed the significance of these mutations with regard to the characteristics of the M protein and progeny virus production. We found that each of the three mutations rendered the M protein insoluble in 0.5% Triton X-100 and altered its subcellular localization, either when ectopically expressed alone using a plasmid-based expression system or when expressed in the context of viral replication. Moreover, each of the three mutations markedly, but not completely, impaired the ability of MV to produce cell-free progeny virus, with the degree of impairment being the same as for all three mutations together. These results suggest the possibility that the changes in the solubility and subcellular localization of the M protein determine the ability to produce cell-free progeny virus, at least to some extent, and play a role in the pathogenicity of variants causing SSPE.
Jiang
Da-Peng
DP
Division of Microbiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, Japan.
Ide
Yoshi-Hiro
YH
Nagano-Fujii
Motoko
M
Shoji
Ikuo
I
Hotta
Hak
H
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000737:chemistry; D006801:Humans; D008459:Measles virus / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D020125:Mutation, Missense; D017354:Point Mutation; D012995:Solubility; D013344:Subacute Sclerosing Panencephalitis / Q000821:virology*; D014709:Vero Cells; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics*; D014779:Virus Replication
D014764:Viral Proteins