Theiler's virus persistence and demyelination in major histocompatibility complex class II-deficient mice

M. Kariuki Njenga, Kevin D. Pavelko, Jeanine Baisch, Xiaoqi Lin, Chella David, Julian Leibowitz, Moses Rodriguez

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Abstract

Mice with targeted disruption of the A(β) gene of major histocompatibility complex class II molecules (Ab(o)) were used to investigate the role of class II gene products in resistance or susceptibility to virus-induced chronic demyelination in the central nervous system (CNS). Class II-deficient mice from the resistant H-2b [H-2b(Ab(o))] and nonmutant H-2b backgrounds were infected with Theiler's murine encephalomyelitis virus intracerebrally and examined for CNS virus persistence, demyelination, and neurologic clinical signs. Virus titers measured by plaque assays showed that 8 of 10 normally resistant nonmutant H- 2b mice had cleared the virus within 21 days, whereas the other 2 mice had low titers. In contrast, all class II-deficient Ab(o) mice had high virus titers for up to 90 days after infection (4.30 log10 to 6.18 log10 PFU per g of CNS tissue). Virus antigens and RNA were localized to the brains (cortex, hippocampus, thalamus, and brain stem) and spinal cords of Ab(o) mice. Colocalization identified persistent Theiler's murine encephalomyelitis virus in oligodendrocytes and astrocytes but not in macrophages. There was demyelination in 11 of 23 and 6 of 9 Ab(o) mice 45 and 90 days after virus infection, respectively, whereas no demyelination was observed in infected nonmutant H-2b mice. Demyelinating lesions in Ab(o) mice showed virus- specific CD8+ T cells and macrophages but no CD4+ T cells. Spasticity and paralysis were observed in chronically infected Ab(o) mice but not in the nonmutant H-2b mice. These findings demonstrate that class II gene products are required for virus clearance from the CNS but not for demyelination and neurulogic disease.

Original languageEnglish (US)
Pages (from-to)1729-1737
Number of pages9
JournalJournal of virology
Volume70
Issue number3
StatePublished - Feb 27 1996

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Kariuki Njenga, M., Pavelko, K. D., Baisch, J., Lin, X., David, C., Leibowitz, J., & Rodriguez, M. (1996). Theiler's virus persistence and demyelination in major histocompatibility complex class II-deficient mice. Journal of virology, 70(3), 1729-1737.