Glycan engagement dictates hydrocephalus induction by serotype 1 reovirus

MBio
Jennifer E Stencel-BaerenwaldTerence S Dermody

Abstract

Receptors expressed on the host cell surface adhere viruses to target cells and serve as determinants of viral tropism. Several viruses bind cell surface glycans to facilitate entry, but the contribution of specific glycan moieties to viral disease is incompletely understood. Reovirus provides a tractable experimental model for studies of viral neuropathogenesis. In newborn mice, serotype 1 (T1) reovirus causes hydrocephalus, whereas serotype 3 (T3) reovirus causes encephalitis. T1 and T3 reoviruses engage distinct glycans, suggesting that glycan-binding capacity contributes to these differences in pathogenesis. Using structure-guided mutagenesis, we engineered a mutant T1 reovirus incapable of binding the T1 reovirus-specific glycan receptor, GM2. The mutant virus induced substantially less hydrocephalus than wild-type virus, an effect phenocopied by wild-type virus infection of GM2-deficient mice. In comparison to wild-type virus, yields of mutant virus were diminished in cultured ependymal cells, the cell type that lines the brain ventricles. These findings suggest that GM2 engagement targets reovirus to ependymal cells in mice and illuminate the function of glycan engagement in reovirus serotype-dependent disease. Receptor ...Continue Reading

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Dec 30, 2015·Viruses·Vera KempDiana J M van den Wollenberg
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Sep 1, 2017·Current Clinical Microbiology Reports·Bernardo A Mainou

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Datasets Mentioned

BETA
GM2

Methods Mentioned

BETA
X-ray
saturation transfer difference nuclear magnetic resonance
flow cytometry
reverse transcription-PCR
electrophoresis

Software Mentioned

MatLab

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