Ganglioside and Non-ganglioside Mediated Host Responses to the Mouse Polyomavirus

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Biological and structural studies have combined to give a detailed understanding of how the mouse polyomavirus binds to sialyloligosaccharides, how polymorphisms in the sialic acid binding pocket of the major virus capsid protein constitute important determinants of pathogenicity, and how gangliosides function as receptors for cell entry and infection by the virus. We used mice with knockouts in defined ganglioside biosynthetic pathways to determine whether gangliosides alone suffice to mediate lethal infection in the intact host and whether non-gangliosides are also recognized by the virus and utilized for important physiological responses. We confirmed the requirement of specific gangliosides for infection and determined that not all gangliosides that bind in vitro serve as receptors in vivo. Results also revealed two physiologically important responses that do not require MuPyV-ganglioside interactions: i) rapid induction of c-fos in fibroblasts as an early step in cell cycle progression on which the virus depends for its own replication, and ii). activation of cytokine secretion by antigen presenting cells as a critical innate immune response to the virus. We infer that these responses are mediated by non-ganglioside receptors bearing sialic acid. These results serve to illustrate the multiplicity of MuPyV receptors and the complexity of virus-cell surface interactions.

Vyšlo v časopise: Ganglioside and Non-ganglioside Mediated Host Responses to the Mouse Polyomavirus. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005175
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005175

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