PMID- 10860577
OWN - NLM
STAT- MEDLINE
DCOM- 20000830
LR  - 20181113
IS  - 1044-7431 (Print)
IS  - 1095-9327 (Electronic)
IS  - 1044-7431 (Linking)
VI  - 15
IP  - 6
DP  - 2000 Jun
TI  - HLA-DQ polymorphism influences progression of demyelination and neurologic 
      deficits in a viral model of multiple sclerosis.
PG  - 495-509
AB  - The importance of genetic susceptibility in determining the progression of 
      demyelination and neurologic deficits is a major focus in neuroscience. We 
      studied the influence of human leukocyte antigen (HLA)-DQ polymorphisms on 
      disease course and neurologic impairment in virus-induced demyelination. HLA-DQ6 
      or DQ8 was inserted as a transgene into mice lacking endogenous expression of MHC 
      class I (beta(2)m) and class II (H2-A(beta)) molecules. Following Theiler's 
      murine encephalomyelitis virus (TMEV) infection, we assessed survival, virus 
      persistence, demyelination, and clinical disease. Mice lacking expression of 
      endogenous class I and class II molecules (beta(2)m(o) Abeta(o) mice) died 3 to 4 
      weeks postinfection (p.i.) due to overwhelming virus replication in neurons. 
      beta(2)m(o) Abeta(o) DQ6 and beta(2)m(o) Abeta(o) DQ8 mice had increased survival 
      and decreased gray matter disease and virus replication compared to nontransgenic 
      littermate controls. Both beta(2)m(o) Abeta(o) DQ6 and beta(2)m(o) Abeta(o) DQ8 
      mice developed chronic virus persistence in glial cells of the white matter of 
      the spinal cord, with greater numbers of virus antigen-positive cells in 
      beta(2)m(o) Abeta(o) DQ8 than in beta(2)m(o) Abeta(o) DQ6 mice. At day 45 p.i., 
      the demyelinating lesions in the spinal cord of beta(2)m(o) Abeta(o) DQ8 were 
      larger than those in the beta(2)m(o) Abeta(o) DQ6 mice. Earlier and more profound 
      neurologic deficits were observed in beta(2)m(o) Abeta (o) DQ8 mice compared to 
      beta(2)m(o) Abeta(o) DQ6 mice, although by 120 days p.i. both strains of mice 
      showed similar extent of demyelination and neurologic deficits. Delayed-type 
      hypersensitivity and antibody responses to TMEV demonstrated that the mice 
      mounted class II-mediated cellular and humoral immune responses. The results are 
      consistent with the hypothesis that rates of progression of demyelination and 
      neurologic deficits are related to the differential ability of DQ6 and DQ8 
      transgenes to modulate the immune response and control virus.
CI  - Copyright 2000 Academic Press.
FAU - Pavelko, K D
AU  - Pavelko KD
AD  - Department of Immunology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, 
      55905, USA.
FAU - Drescher, K M
AU  - Drescher KM
FAU - McGavern, D B
AU  - McGavern DB
FAU - David, C S
AU  - David CS
FAU - Rodriguez, M
AU  - Rodriguez M
LA  - eng
GR  - R01 NS032129/NS/NINDS NIH HHS/United States
GR  - R37 AI014764/AI/NIAID NIH HHS/United States
GR  - R01 AI014764/AI/NIAID NIH HHS/United States
GR  - F31 MH012120/MH/NIMH NIH HHS/United States
GR  - NS 32129/NS/NINDS NIH HHS/United States
GR  - AI14764/AI/NIAID NIH HHS/United States
GR  - NS 24180/NS/NINDS NIH HHS/United States
GR  - R01 NS024180/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Antigens, Viral)
RN  - 0 (HLA-DQ Antigens)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Antibody Formation/genetics
MH  - Antigens, Viral/analysis
MH  - Brain/immunology/virology
MH  - Cardiovirus Infections/*genetics/immunology/mortality
MH  - Chronic Disease
MH  - Demyelinating Diseases/genetics/immunology
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Genetic Predisposition to Disease
MH  - HLA-DQ Antigens/*genetics
MH  - Humans
MH  - Hypersensitivity, Delayed/immunology/virology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Motor Activity
MH  - Multiple Sclerosis/*genetics/immunology
MH  - Nerve Fibers/immunology/virology
MH  - *Polymorphism, Genetic
MH  - Postural Balance
MH  - Spinal Cord/immunology/virology
MH  - Survival Analysis
MH  - *Theilovirus
MH  - Virus Replication/immunology
PMC - PMC5450945
MID - NIHMS859410
EDAT- 2000/06/22 10:00
MHDA- 2000/09/02 11:01
PMCR- 2017/05/31
CRDT- 2000/06/22 10:00
PHST- 2000/06/22 10:00 [pubmed]
PHST- 2000/09/02 11:01 [medline]
PHST- 2000/06/22 10:00 [entrez]
PHST- 2017/05/31 00:00 [pmc-release]
AID - S1044-7431(00)90843-1 [pii]
AID - 10.1006/mcne.2000.0843 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2000 Jun;15(6):495-509. doi: 10.1006/mcne.2000.0843.