Human class I major histocompatibility complex alleles determine central nervous system injury versus repair

Bharath Wootla, Aleksandar Denic, Jens O. Watzlawik, Arthur E. Warrington, Laurie J. Zoecklein, Louisa M. Papke-Norton, Chella David, Moses Rodriguez

Research output: Contribution to journalArticle

Abstract

Background: We investigated the role of human HLA class I molecules in persistent central nervous system (CNS) injury versus repair following virus infection of the CNS. Methods: Human class I A11+ and B27+ transgenic human beta-2 microglobulin positive (Hβ2m+) mice of the H-2 b background were generated on a combined class I-deficient (mouse beta-2 microglobulin deficient, β2m0) and class II-deficient (mouse Aβ0) phenotype. Intracranial infection with Theiler's murine encephalomyelitis virus (TMEV) in susceptible SJL mice results in acute encephalitis with prominent injury in the hippocampus, striatum, and cortex. Results: Following infection with TMEV, a picornavirus, the Aβ0.β2m0 mice lacking active immune responses died within 18 to 21 days post-infection. These mice showed severe encephalomyelitis due to rapid replication of the viral genome. In contrast, transgenic Hβ2m mice with insertion of a single human class I MHC gene in the absence of human or mouse class II survived the acute infection. Both A11+ and B27+ mice significantly controlled virus RNA expression by 45 days and did not develop late-onset spinal cord demyelination. By 45 days post-infection (DPI), B27+ transgenic mice showed almost complete repair of the virus-induced brain injury, but A11+ mice conversely showed persistent severe hippocampal and cortical injury. Conclusions: The findings support the hypothesis that the expression of a single human class I MHC molecule, independent of persistent virus infection, influences the extent of sub frequent chronic neuronal injury or repair in the absence of a class II MHC immune response.

Original languageEnglish (US)
Article number293
JournalJournal of Neuroinflammation
Volume13
Issue number1
DOIs
StatePublished - Nov 17 2016

Keywords

  • Human leukocyte antigen
  • Major histocompatibility complex
  • Picornavirus
  • Theiler's murine encephalomyelitis virus
  • Virus persistence

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Wootla, B., Denic, A., Watzlawik, J. O., Warrington, A. E., Zoecklein, L. J., Papke-Norton, L. M., David, C., & Rodriguez, M. (2016). Human class I major histocompatibility complex alleles determine central nervous system injury versus repair. Journal of Neuroinflammation, 13(1), [293]. https://doi.org/10.1186/s12974-016-0759-4