Unknown,Transcriptomics,Genomics,Proteomics

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Genes induced after BDV infection in Sprague Dawley and Lewis rats

ABSTRACT: Borna Disease Virus (BDV) is a neurotropic virus that persistently infects neurons in the central nervous system of various hosts, including rats. Although BDV is known to be an IFN sensitive virus, determination of the cellular mRNA transcript levels revealed the induction of IFN-stimulated genes in organotypic rat hippocampus slice cultures, raising the question how BDV evades this innate immune response. Using rat Mx protein as a specific marker for IFN-induced gene products, we could show that neurons lack detectable levels of Mx in these BDV infected cultures, whereas astrocytes and microglial cells were Mx positive. Neurons remained Mx negative after treatment of uninfected hippocampus cultures as well as primary dissociated neuronal cultures with high concentrations of IFN-M-NM-1. This non-responsiveness correlated with a lack of a detectable nuclear translocation of pSTAT1 in rat neurons. Consistently, IFN treatment of BDV-infected rat neurons did not prevent the establishment of a viral persistence in the neuronal tissue. However, IFN treatment efficiently prevented vesicular stomatitis virus (VSV) replication, indicating that these cells can mount a weak innate immune response. In contrast, IFN treatment of mouse neurons resulted in the upregulation of Mx1 proteins and inhibition of BDV replication, indicating species-specific differences in the IFN response in neurons between mice and rats. Rat neurons may therefore represent the ideal cell type for BDV to evade the innate immune in the central nervous system. To determine the mRNA levels in the hippocampal slice cultures after BDV infection in Sprague Dawley and Lewis rats Hippocampal slice cultures were prepared from newborn Lewis and SD rats (P0-P2). Half of the samples remained uninfected, whereas the other half was infected with 1000 focus forming units (FFU) of BDV strain He/80. Total RNA from a pool of 12 slice cultures was prepared

ORGANISM(S): Rattus norvegicus

SUBMITTER: Martin Schwemmle

PROVIDER: E-GEOD-41540 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Absence of a robust innate immune response in rat neurons facilitates persistent infection of Borna disease virus in neuronal tissue.

Lin Chia-Ching CC Wu Yuan-Ju YJ Heimrich Bernd B Schwemmle Martin M

Cellular and molecular life sciences : CMLS 20130623 22

Borna disease virus (BDV) persistently infects neurons of the central nervous system of various hosts, including rats. Since type I IFN-mediated antiviral response efficiently blocks BDV replication in primary rat embryo fibroblasts, it has been speculated that BDV is not effectively sensed by the host innate immune system in the nervous system. To test this assumption, organotypical rat hippocampal slice cultures were infected with BDV for up to 4 weeks. This resulted in the secretion of IFN an ...[more]

PMID: 23793543

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Project description:To examine the influence cellular and genetics on the procainamide-induced autoimmune response in spleens we compared rats that are genetically Th2-predisposed (Brown Norway), Th1-predisposed (Lewis) or not genetically predisposed (Sprague Dawley). Rats were treated with procainamide three times per week. From the second week, blood samples were taken once a week for antinuclear antibody (ANA) detection. At 56d after treatment, rats were sacrificed and spleens samples were collected for microarray test and histopathology examination. Frequencies of T cell subsets and B cells in rat spleen were measured to assess the effects on splenocyte. Also, 12 serum cytokines/chemokines were determined to explored the Th1/Th2 cytokine pattern after treatment. We found that ANA were makedly elevated in BN and SD rats, while the elevated appeared earlier in BN rats, and the magnitude of its increase were much higher than that of SD rats. There was no marked change in serum ANA in Lewis rats. Histopathological analysis indicated that spleen weight increased significantly both in BN and SD rats after stimulated with procainamide. No significant changes in spleen weight and lesions were observed in Lewis rats. We also found the percentage of CD86 positive cells in spleen of BN rats was significantly increased, while the percentage of CD4+CD25+ cells was decreased in BN rats. In addition, percentage of CD11b/c positive cells were decreased, and the levels of Th-2 (IL-10), Th-1 type cytokine (IFN-γ) and chemokine (IL-1β) in serum were markedly elevated both in BN and SD rats after treatment. Th-2 type cytokine (IL-4, IL-6) in serum were markedly increased only in BN rats. Furthermore, similar immune mechanisms were found in BN and SD rat, and the altered genes were mainly associated in immune response, and inflammatory response. However, the number of differentially expressed genes (DEGs) in BN rats was higher than that in SD rats. Overall, we revealed significant differences in response to autoimmunity induced by procainamide among three strains rats, the BN rats was the most sensitive one, SD rats exhibited less sensitive while Lewis resistance to procainamide. Much more pronounced of Th2-type responses and more complex DEGs involved in immune regulation and response in BN rats might contribute to its susceptible to drug-induced lupus erythematosus. Moreover, similar immune mechanisms were found between BN and SD rat, which suggesting that these changes would served as the potential bridge biomarkers to predict drug-induced autoimmune reactions among species. The results may also provide a scientic basis for the high sensitivity of BN rats in prediction immunotoxicity in preclinical studies.

Dataset Information

Genes induced after BDV infection in Sprague Dawley and Lewis rats

Publications

Absence of a robust innate immune response in rat neurons facilitates persistent infection of Borna disease virus in neuronal tissue.

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