Viral expression of CCL2 is sufficient to induce demyelination in RAG1-/- mice infected with a neurotropic coronavirus

Taeg S Kim; Stanley Perlman

doi:10.1128/JVI.79.11.7113-7120.2005

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Viral expression of CCL2 is sufficient to induce demyelination in RAG1-/- mice infected with a neurotropic coronavirus

Journal article

Open access

Peer reviewed

Viral expression of CCL2 is sufficient to induce demyelination in RAG1-/- mice infected with a neurotropic coronavirus

Taeg S Kim and Stanley Perlman

Journal of virology, Vol.79(11), pp.7113-7120

06/2005

DOI: 10.1128/JVI.79.11.7113-7120.2005

PMCID: PMC1112157

PMID: 15890951

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https://europepmc.org/articles/pmc1112157View

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Abstract

Mouse hepatitis virus strain JHM causes a chronic demyelinating disease in susceptible strains of rodents. Demyelination does not develop in infected RAG1-/- (recombination activation gene-deficient) mice but can be induced by several experimental interventions, including adoptive transfer of virus-specific T cells or antibodies. A common feature of demyelination in these models is extensive infiltration of macrophages/microglia into the white matter. The data obtained thus far do not indicate whether macrophage/microglia infiltration, in the absence of T cells or antibody, is sufficient to mediate demyelination. To determine whether the expression of a single macrophage chemoattractant, in the context of virus infection, could initiate the demyelinating process, we engineered a recombinant coronavirus that expressed the chemokine CCL2/monocyte chemoattractant protein-1. CCL2 has been implicated in macrophage infiltration into the central nervous system and is involved in demyelination in many experimental models of demyelination. Extensive macrophage/microglia infiltration and demyelination has developed in RAG1-/- mice infected with this recombinant virus. Thus, these results suggest that the minimal requirement for demyelination is increased expression of a single macrophage-attracting chemokine in the context of an inflammatory milieu, such as that induced by a viral infection.

DNA, Recombinant - genetics

Gene Expression

Humans

RNA, Messenger - genetics

Chemokine CCL2 - genetics

Recombinant Proteins - genetics

Murine hepatitis virus - pathogenicity

RNA, Messenger - metabolism

Homeodomain Proteins - genetics

Mice, Knockout

RNA - genetics

Murine hepatitis virus - immunology

Animals

Recombinant Proteins - immunology

Recombination, Genetic

Base Sequence

Chemokine CCL2 - physiology

Demyelinating Diseases - etiology

Mice

HeLa Cells

Coronavirus Infections - etiology

Homeodomain Proteins - physiology

Murine hepatitis virus - genetics

RNA - metabolism

Details

Title: Subtitle: Viral expression of CCL2 is sufficient to induce demyelination in RAG1-/- mice infected with a neurotropic coronavirus
Creators: Taeg S Kim - Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242, USA
Stanley Perlman
Resource Type: Journal article
Publication Details: Journal of virology, Vol.79(11), pp.7113-7120
DOI: 10.1128/JVI.79.11.7113-7120.2005
PMID: 15890951
PMCID: PMC1112157
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: United States
Grant note: NS-40438 / NINDS NIH HHS R01 NS040438 / NINDS NIH HHS
Language: English
Date published: 06/2005
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777478202771

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