Diminished Reovirus Capsid Stability Alters Disease Pathogenesis and Littermate Transmission

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Following attachment and internalization, viruses disassemble to complete the entry process, establish infection, and cause disease. Viral capsid stability balances on a fulcrum, as viruses must be sufficiently stable in the environment to reach the host yet also uncoat efficiently once the target cell barrier has been breached. Reoviruses are useful models to understand the relationship between viral entry and pathogenesis. Residues within reovirus outer-capsid protein σ3 influence capsid stability, but the function of capsid stability in disease pathogenesis was not known. We found that serotype 1 and serotype 3 reovirus variants with diminished capsid stability attributable to a single amino change in σ3 displayed enhanced lethality in newborn mice following peroral and intramuscular inoculation, respectively. In the serotype 1 background, this variant caused increased damage to cardiac tissue and increased elaboration of inflammatory mediators in comparison to wild-type virus. Remarkably, diminished capsid stability also enhanced the spread of virus between inoculated and uninoculated littermates. Taken together, these findings define a new virulence determinant for reovirus and shed light on general principles of viral pathogenesis for nonenveloped viruses.

Vyšlo v časopise: Diminished Reovirus Capsid Stability Alters Disease Pathogenesis and Littermate Transmission. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004693
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004693

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