Enhanced virulence mediated by the murine coronavirus, mouse hepatitis virus strain JHM, is associated with a glycine at residue 310 of the spike glycoprotein

Evelena Ontiveros; Taeg S Kim; Thomas M Gallagher; Stanley Perlman

doi:10.1128/JVI.77.19.10260-10269.2003

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Enhanced virulence mediated by the murine coronavirus, mouse hepatitis virus strain JHM, is associated with a glycine at residue 310 of the spike glycoprotein

Journal article

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Peer reviewed

Enhanced virulence mediated by the murine coronavirus, mouse hepatitis virus strain JHM, is associated with a glycine at residue 310 of the spike glycoprotein

Evelena Ontiveros, Taeg S Kim, Thomas M Gallagher and Stanley Perlman

Journal of virology, Vol.77(19), pp.10260-10269

10/2003

DOI: 10.1128/JVI.77.19.10260-10269.2003

PMCID: PMC228498

PMID: 12970410

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Abstract

The coronavirus, mouse hepatitis virus strain JHM, causes acute and chronic neurological diseases in rodents. Here we demonstrate that two closely related virus variants, both of which cause acute encephalitis in susceptible strains of mice, cause markedly different diseases if mice are protected with a suboptimal amount of an anti-JHM neutralizing antibody. One strain, JHM.SD, caused acute encephalitis, while infection with JHM.IA resulted in no acute disease. Using recombinant virus technology, we found that the differences between the two viruses mapped to the spike (S) glycoprotein and that the two S proteins differed at four amino acids. By engineering viruses that differed by only one amino acid, we identified a serine-to-glycine change at position 310 of the S protein (S310G) that recapitulated the more neurovirulent phenotype. The increased neurovirulence mediated by the virus encoding glycine at position S310 was not associated with a different tropism within the central nervous system (CNS) but was associated with increased lateral spread in the CNS, leading to significantly higher brain viral titers. In vitro studies revealed that S310G was associated with decreased S1-S2 stability and with enhanced ability to mediate infection of cells lacking the primary receptor for JHM ("receptor-independent spread"). These enhanced fusogenic properties of viruses encoding a glycine at position 310 of the S protein may contribute to spread within the CNS, a tissue in which expression of conventional JHM receptors is low.

Cricetinae

Membrane Fusion

Membrane Glycoproteins - chemistry

Virulence

Structure-Activity Relationship

Glycine

Murine hepatitis virus - pathogenicity

Viral Envelope Proteins - toxicity

Spike Glycoprotein, Coronavirus

Animals

Membrane Glycoproteins - toxicity

Viral Envelope Proteins - chemistry

Mice

Details

Title: Subtitle: Enhanced virulence mediated by the murine coronavirus, mouse hepatitis virus strain JHM, is associated with a glycine at residue 310 of the spike glycoprotein
Creators: Evelena Ontiveros - Interdisciplinary Program in Immunology, University of Iowa, Iowa City, Iowa 52242, USA
Taeg S Kim
Thomas M Gallagher
Stanley Perlman
Resource Type: Journal article
Publication Details: Journal of virology, Vol.77(19), pp.10260-10269
DOI: 10.1128/JVI.77.19.10260-10269.2003
PMID: 12970410
PMCID: PMC228498
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: United States
Grant note: F31 AI10348 / NIAID NIH HHS NS 40438 / NINDS NIH HHS NS 365092 / NINDS NIH HHS NS31616 / NINDS NIH HHS R01 NS040438 / NINDS NIH HHS
Language: English
Date published: 10/2003
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777476502771

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