title: Human class I major histocompatibility complex alleles determine central nervous system injury versus repair.
abstract: 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.
  
  
  
  Human class I A11+and B27+transgenic human beta-2 microglobulin positive (Hβ2m+) mice of the H-2bbackground 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.
  
  
  
  Following infection with TMEV, a picornavirus, the Aβ0.β2m0mice 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.
  
  
  
  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.
authors.affiliation: Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.|Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.|Center for Regenerative Medicine, Neuroregeneration, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Bharath
authors.initials: B
authors.lastname: Wootla
authors.affiliation: Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.|Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Denic
authors.affiliation: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road S, Jacksonville, FL, 32224, USA.
authors.forename: Jens O
authors.initials: JO
authors.lastname: Watzlawik
authors.affiliation: Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.|Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Warrington
authors.affiliation: Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.|Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Zoecklein
authors.affiliation: Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.|Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Louisa M
authors.initials: LM
authors.lastname: Papke-Norton
authors.affiliation: Department of Immunology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Chella
authors.initials: C
authors.lastname: David
authors.affiliation: Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Rodriguez.Moses@mayo.edu.|Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Rodriguez.Moses@mayo.edu.|Department of Immunology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Rodriguez.Moses@mayo.edu.
authors.forename: Moses
authors.identifier: 0000-0001-6328-6497
authors.initials: M
authors.lastname: Rodriguez
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D018188:Cardiovirus Infections / Q000473:pathology*; D002490:Central Nervous System / Q000473:pathology* / Q000821:virology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D059870:HLA-A11 Antigen / Q000378:metabolism; D015796:HLA-B27 Antigen / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger; D017945:Theilovirus / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D059870:HLA-A11 Antigen; D015796:HLA-B27 Antigen; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D014764:Viral Proteins
keywords: Human leukocyte antigen; Major histocompatibility complex; Picornavirus; Theiler’s murine encephalomyelitis virus; Virus persistence