title: Canine distemper virus matrix protein influences particle infectivity, particle composition, and envelope distribution in polarized epithelial cells and modulates virulence.
abstract: In paramyxoviruses, the matrix (M) protein mediates the interaction between the envelope and internal proteins during particle assembly and egress. In measles virus (MeV), M mutations, such as those found in subacute sclerosing panencephalitis (SSPE) strains, and differences in vaccine and wild-type M proteins can affect the strength of interaction with the envelope glycoproteins, assembly efficiency, and spread. However, the contribution of the M protein to the replication and pathogenesis of the closely related canine distemper virus (CDV) has not been characterized. To this end this, we generated a recombinant wild-type CDV carrying a vaccine strain M protein. The recombinant virus retained the parental growth phenotype in VerodogSLAMtag cells, but displayed an increased particle-to-infectivity ratio very similar to that of the vaccine strain, likely due to inefficient H protein incorporation. Even though infectious virus was released only from the apical surface, consistent with the release polarity of the wild-type CDV strain, envelope protein distribution in polarized epithelial cells reproduced the bipolar pattern seen in vaccine strain-infected cells. Most notably, the chimeric virus was completely attenuated in ferrets and caused only a mild and transient leukopenia, indicating that the differences in particle infectivity and envelope protein sorting mediated by the vaccine M protein contribute importantly to vaccine strain attenuation.
authors.affiliation: Institute of Virology, Philipps University Marburg, Marburg, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Dietzel
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Anderson
authors.forename: Alexandre
authors.initials: A
authors.lastname: Castan
authors.forename: Veronika
authors.initials: V
authors.lastname: von Messling
authors.forename: Andrea
authors.initials: A
authors.lastname: Maisner
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004217:Distemper Virus, Canine / Q000472:pathogenicity*; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000821:virology; D005289:Ferrets; D006801:Humans; D014764:Viral Proteins / Q000502:physiology*; D014774:Virulence
chemical_list: D014764:Viral Proteins