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Borna disease virus-induced neuronal degeneration dependent on host genetic background and prevented by soluble factors.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2013 Jan 29; Vol. 110 (5), pp. 1899-904. Date of Electronic Publication: 2013 Jan 14. - Publication Year :
- 2013
-
Abstract
- Infection of newborn rats with Borne disease virus (BDV) results in selective degeneration of granule cell neurons of the dentate gyrus (DG). To study cellular countermechanisms that might prevent this pathology, we screened for rat strains resistant to this BDV-induced neuronal degeneration. To this end, we infected hippocampal slice cultures of different rat strains with BDV and analyzed for the preservation of the DG. Whereas infected cultures of five rat strains, including Lewis (LEW) rats, exhibited a disrupted DG cytoarchitecture, slices of three other rat strains, including Sprague-Dawley (SD), were unaffected. However, efficiency of viral replication was comparable in susceptible and resistant cultures. Moreover, these rat strain-dependent differences in vulnerability were replicated in vivo in neonatally infected LEW and SD rats. Intriguingly, conditioned media from uninfected cultures of both LEW and SD rats could prevent BDV-induced DG damage in infected LEW hippocampal cultures, whereas infection with BDV suppressed the availability of these factors from LEW but not in SD hippocampal cultures. To gain further insights into the genetic basis for this rat strain-dependent susceptibility, we analyzed DG granule cell survival in BDV-infected cultures of hippocampal neurons derived from the F1 and F2 offspring of the crossing of SD and LEW rats. Genome-wide association analysis revealed one resistance locus on chromosome (chr) 6q16 in SD rats and, surprisingly, a locus on chr3q21-23 that was associated with susceptibility. Thus, BDV-induced neuronal degeneration is dependent on the host genetic background and is prevented by soluble protective factors in the disease-resistant SD rat strain.
- Subjects :
- Animals
Animals, Newborn
Biological Factors chemistry
Biological Factors pharmacology
Brain-Derived Neurotrophic Factor pharmacology
Cell Survival drug effects
Chromosome Mapping
Chromosomes, Mammalian genetics
Culture Media, Conditioned chemistry
Culture Media, Conditioned pharmacology
Dentate Gyrus metabolism
Dentate Gyrus pathology
Disease Resistance genetics
Female
Hippocampus metabolism
Hippocampus pathology
Hippocampus virology
Host-Pathogen Interactions
Male
Nerve Degeneration genetics
Nerve Degeneration prevention & control
Neurons metabolism
Neurons pathology
Polymorphism, Single Nucleotide
Rats
Rats, Inbred Lew
Rats, Sprague-Dawley
Solubility
Species Specificity
Tissue Culture Techniques
Borna disease virus physiology
Dentate Gyrus virology
Nerve Degeneration virology
Neurons virology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 110
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 23319640
- Full Text :
- https://doi.org/10.1073/pnas.1214939110