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Clusters of mutations identified around the matrix (M) protein in many SSPE viruses suppress productive infectious particle release and accelerate cell\u2013cell fusion, which are features of SSPE viruses. It was reported, however, that these defects of M protein function might not be correlated directly with promotion of neurovirulence, although they might enable establishment of persistent infection. Neuropathogenicity is closely related to the character of the viral fusion (F) protein, and amino acid substitution(s) in the F protein of some SSPE viruses confers F protein hyperfusogenicity, facilitating viral propagation in the CNS through cell\u2013cell fusion and leading to neurovirulence. The F protein of an SSPE virus Kobe-1 strain, however, displayed only moderately enhanced fusion activity and required additional mutations in the M protein for neuropathogenicity in mice. We demonstrated here the mechanism for the M protein of the Kobe-1 strain supporting the fusion activity of the F protein and cooperatively inducing neurovirulence, even though each protein, independently, has no effect on virulence. The occurrence of SSPE has been estimated recently as one in several thousand in children who acquired measles under the age of 5\u2009years, markedly higher than reported previously. The probability of a specific mutation (or mutations) occurring in the F protein conferring hyperfusogenicity and neuropathogenicity might not be sufficient to explain the high frequency of SSPE. The induction of neurovirulence by M protein synergistically with moderately fusogenic F protein could account for the high frequency of SSPE.<\/jats:p>","DOI":"10.1099\/jgv.0.001682","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T12:23:10Z","timestamp":1634127790000},"source":"Crossref","is-referenced-by-count":10,"title":["M protein of subacute sclerosing panencephalitis virus, synergistically with the F protein, plays a crucial role in viral neuropathogenicity"],"prefix":"10.1099","volume":"102","author":[{"given":"Yuto","family":"Satoh","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurara","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, 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