Absence of spontaneous central nervous system remyelination in class II- deficient mice infected with Theiler's virus

M. Kariuki Njenga, Paul D. Murray, Dorian McGavern, Xiaoqi Lin, Kristen M. Drescher, Moses Rodriguez

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

We previously showed that Theiler's murine encephalomyelitis virus (TMEV)-infected major histocompatibility complex (MHC) class II-deficient mice develop both demyelination and neurologic deficits, whereas MHC class I- deficient mice develop demyelination but no neurologic deficits. The absence of neurologic deficits in the class I-deficient mice was associated with preserved sodium channel densities in demyelinated lesions, a relative preservation of axons, and extensive spontaneous remyelination. In this study, we investigated whether TMEV-infected class II-deficient mice, which have an identical genetic background (C57BL/6 x 129) as the class I-deficient mice, have preserved axons and spontaneous myelin repair following chronic TMEV-infection. Both class I- and class II-deficient mice showed similar extents of demyelination of the spinal cord white matter 4 months after TMEV infection. However, the class I-deficient mice demonstrated remyelination by oligodendrocytes, whereas class II-deficient mice showed minimal if any myelin repair. Demyelinated lesions, characterized by inflammatory infiltrates in both mutants, revealed disruption of axons in class II- but not class I-deficient mice. Further characterization revealed that even though class II-deficient mice lacked TMEV-specific IgG, they had virus- specific IgM, which, however, did not neutralize TMEV in vitro. In addition, class II-deficient mice developed TMEV-specific cytotoxic T-lymphocytes in the CNS during the acute (7 days) disease, but these cytotoxic lymphocytes were not present in the chronic stage of disease, despite a high titer of infectious virus throughout the disease. We envision that the presence of demyelination, high virus titer, absence of remyelination, and axonal disruption in chronically infected class II-deficient mice contributes to the development of paralytic disease.

Original languageEnglish (US)
Pages (from-to)78-91
Number of pages14
JournalJournal of Neuropathology and Experimental Neurology
Volume58
Issue number1
StatePublished - Jan 1999

Fingerprint

Theilovirus
Central Nervous System
Demyelinating Diseases
Virus Diseases
Neurologic Manifestations
Axons
Myelin Sheath
Major Histocompatibility Complex
Sodium Channels
Oligodendroglia
Cytotoxic T-Lymphocytes
Viral Load

Keywords

  • Axonal damage
  • Cytotoxic CD8+ T cells
  • Demyelination
  • MHC class I
  • MHC Class II
  • Remyelination
  • Theiler's murine encephalomyelitis virus

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Absence of spontaneous central nervous system remyelination in class II- deficient mice infected with Theiler's virus. / Njenga, M. Kariuki; Murray, Paul D.; McGavern, Dorian; Lin, Xiaoqi; Drescher, Kristen M.; Rodriguez, Moses.

In: Journal of Neuropathology and Experimental Neurology, Vol. 58, No. 1, 01.1999, p. 78-91.

Research output: Contribution to journalArticle

Njenga, M. Kariuki ; Murray, Paul D. ; McGavern, Dorian ; Lin, Xiaoqi ; Drescher, Kristen M. ; Rodriguez, Moses. / Absence of spontaneous central nervous system remyelination in class II- deficient mice infected with Theiler's virus. In: Journal of Neuropathology and Experimental Neurology. 1999 ; Vol. 58, No. 1. pp. 78-91.
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