title: Intergenotypic replacement of lyssavirus matrix proteins demonstrates the role of lyssavirus M proteins in intracellular virus accumulation.
abstract: Lyssavirus assembly depends on the matrix protein (M). We compared lyssavirus M proteins from different genotypes for their ability to support assembly and egress of genotype 1 rabies virus (RABV). Transcomplementation of M-deficient RABV with M from European bat lyssavirus (EBLV) types 1 and 2 reduced the release of infectious virus. Stable introduction of the heterogenotypic M proteins into RABV led to chimeric viruses with reduced virus release and intracellular accumulation of virus genomes. Although the chimeras indicated genotype-specific evolution of M, rapid selection of a compensatory mutant suggested conserved mechanisms of lyssavirus assembly and the requirement for only few adaptive mutations to fit the heterogenotypic M to a RABV backbone. Whereas the compensatory mutant replicated to similar infectious titers as RABV M-expressing virus, ultrastructural analysis revealed that both nonadapted EBLV M chimeras and the compensatory mutant differed from RABV M expressing viruses in the lack of intracellular viruslike structures that are enveloped and accumulate in cisterna of the degranulated and dilated rough endoplasmic reticulum compartment. Moreover, all viruses were able to bud at the plasma membrane. Since the lack of the intracellular viruslike structures correlated with the type of M protein but not with the efficiency of virus release, we hypothesize that the M proteins of EBLV-1 and RABV differ in their target membranes for virus assembly. Although the biological function of intracellular assembly and accumulation of viruslike structures in the endoplasmic reticulum remain unclear, the observed differences could contribute to diverse host tropism or pathogenicity.
authors: Friedrich-Loeffler-Institut, Südufer 10, D-17493 Greifswald-Insel Riems, Germany. stefan.finke@fli.bund.de
authors: Stefan
authors: S
authors: Finke
authors: Harald
authors: H
authors: Granzow
authors: Jose
authors: J
authors: Hurst
authors: Reiko
authors: R
authors: Pollin
authors: Thomas C
authors: TC
authors: Mettenleiter
mesh_terms: D000818:Animals; D002460:Cell Line; D002685:Chiroptera / Q000821:virology; D005816:Genetic Complementation Test; D005838:Genotype; D018114:Lyssavirus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D011820:Rabies virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D011995:Recombination, Genetic; D013045:Species Specificity; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000502:physiology*; D014771:Virion / Q000648:ultrastructure; D014774:Virulence / Q000235:genetics; D019065:Virus Assembly
chemical_list: D014763:Viral Matrix Proteins