Treatment with lipopolysaccharide enhances the pathogenicity of a low- pathogenic variant of Theiler's murine encephalomyelitis virus

J. P. Palma, S. H. Park, B. S. Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Intracerebral infection of susceptible mouse strains with Theiler's murine encephalomyelitis virus (TMEV) results in an immune-mediated demyelinating disease (TMEV-IDD) similar to human multiple sclerosis (MS). Although the etiology of MS remains unknown, a role of an infectious agent has been implicated in its onset. Previously we have shown the ability of bacterial lipopolysaccharide (LPS) to alter susceptibility to TMEV-IDD in genetically resistant C57BL/6 mice. In this study, the potential of LPS to alter pathogenicity of a low/non-pathogenic variant of TMEV was investigated. After intraperitoneal treatment of genetically susceptible SJL/J mice with LPS before and during viral infection, 80-100% of the mice developed clinical symptoms, while without LPS treatment none of the mice were affected. However, clinical severity in these LPS-treated mice was much milder than the level induced by the wild type pathogenic virus. Increased susceptibility to the disease after LPS treatment did not correlate with splenic T cell proliferative responses against viral antigens. However, by reverse transcriptase polymerase chain reaction (RT-PCR) analyses, an early increase in the production of Th1-type proinflammatory cytokine messages (e.g., interferon-γ [IFN-γ] and enhancement of viral persistence was observed in the CNS of LPS-treated, virus-infected animals as compared to mice infected with the variant virus alone. These results indicate that environmental factors such as a bacterial infection (e.g., LPS) promoting proinflammatory cytokine production can significantly enhance the pathogenicity of demyelination induced by a normally non-pathogenic virus.

Original languageEnglish (US)
Pages (from-to)776-785
Number of pages10
JournalJournal of Neuroscience Research
Volume45
Issue number6
DOIs
StatePublished - Sep 15 1996

Keywords

  • Theiler's virus
  • cytokines
  • multiple sclerosis

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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