Treatment with lipopolysaccharide enhances the pathogenicity of a low-pathogenic variant of Theiler's murine encephalomyelitis virus.
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-gamma [IFN-gamma] 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.
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
J P
JP
Palma
S H
SH
Park
B S
BS
Kim
D000818:Animals; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D014644:Genetic Variation; D016056:Immunodominant Epitopes; D015994:Incidence; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011051:Poliomyelitis / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology*; D018417:Th1 Cells; D017945:Theilovirus / Q000235:genetics / Q000472:pathogenicity*
D016207:Cytokines; D016056:Immunodominant Epitopes; D008070:Lipopolysaccharides; D012333:RNA, Messenger