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 language | English (US) |
|---|---|
| Article number | 293 |
| Journal | Journal of Neuroinflammation |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| State | Published - Nov 17 2016 |
Fingerprint
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
Cite this
Human class I major histocompatibility complex alleles determine central nervous system injury versus repair. / Wootla, Bharath; Denic, Aleksandar; Watzlawik, Jens O.; Warrington, Arthur E.; Zoecklein, Laurie J.; Papke-Norton, Louisa M.; David, Chella; Rodriguez, Moses.
In: Journal of Neuroinflammation, Vol. 13, No. 1, 293, 17.11.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human class I major histocompatibility complex alleles determine central nervous system injury versus repair
AU - Wootla, Bharath
AU - Denic, Aleksandar
AU - Watzlawik, Jens O.
AU - Warrington, Arthur E.
AU - Zoecklein, Laurie J.
AU - Papke-Norton, Louisa M.
AU - David, Chella
AU - Rodriguez, Moses
PY - 2016/11/17
Y1 - 2016/11/17
N2 - 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.
AB - 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.
KW - Human leukocyte antigen
KW - Major histocompatibility complex
KW - Picornavirus
KW - Theiler's murine encephalomyelitis virus
KW - Virus persistence
UR - http://www.scopus.com/inward/record.url?scp=85003666517&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85003666517&partnerID=8YFLogxK
U2 - 10.1186/s12974-016-0759-4
DO - 10.1186/s12974-016-0759-4
M3 - Article
VL - 13
JO - Journal of Neuroinflammation
JF - Journal of Neuroinflammation
SN - 1742-2094
IS - 1
M1 - 293
ER -