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The bicolored white-toothed shrew Crocidura leucodon (HERMANN 1780) is an indigenous host of mammalian Borna disease virus.

Dürrwald R, Kolodziejek J, Weissenböck H, Nowotny N - PLoS ONE (2014)

Bottom Line: The search for such a reservoir had been unsuccessful until a few years ago five BDV-infected shrews were found in a BD-endemic area in Switzerland.So far, these data lacked further confirmation.Analyses of behavioral and population features of this shrew species revealed that the bicolored white-toothed shrew may indeed play an important role as an indigenous host of BDV.

View Article: PubMed Central - PubMed

Affiliation: IDT Biologika GmbH (IDT), Dessau-Roβlau, Germany.

ABSTRACT
Borna disease (BD) is a sporadic neurologic disease of horses and sheep caused by mammalian Borna disease virus (BDV). Its unique epidemiological features include: limited occurrence in certain endemic regions of central Europe, yearly varying disease peaks, and a seasonal pattern with higher disease frequencies in spring and a disease nadir in autumn. It is most probably not directly transmitted between horses and sheep. All these features led to the assumption that an indigenous virus reservoir of BDV other than horses and sheep may exist. The search for such a reservoir had been unsuccessful until a few years ago five BDV-infected shrews were found in a BD-endemic area in Switzerland. So far, these data lacked further confirmation. We therefore initiated a study in shrews in endemic areas of Germany. Within five years 107 shrews of five different species were collected. BDV infections were identified in 14 individuals of the species bicolored white-toothed shrew (Crocidura leucodon, HERMANN 1780), all originating from BD-endemic territories. Immunohistological analysis showed widespread distribution of BDV antigen both in the nervous system and in epithelial and mesenchymal tissues without pathological alterations. Large amounts of virus, demonstrated by presence of viral antigen in epithelial cells of the oral cavity and in keratinocytes of the skin, may be a source of infection for natural and spill-over hosts. Genetic analyses reflected a close relationship of the BDV sequences obtained from the shrews with the regional BDV cluster. At one location a high percentage of BDV-positive shrews was identified in four consecutive years, which points towards a self-sustaining infection cycle in bicolored white-toothed shrews. Analyses of behavioral and population features of this shrew species revealed that the bicolored white-toothed shrew may indeed play an important role as an indigenous host of BDV.

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Immunohistochemical staining patterns of different organs with the polyclonal anti-P antibody and the monoclonal antibody Bo18.A. Diffuse immunostaining in the area of the dentate gyrus, brain, anti-P antibody; shrew CL72; B. Diffuse immunostaining in the area of the dentate gyrus, brain, Bo18 Ab; Note slightly different immunostaining with presence of nuclear signals with anti-P antibody and absence of nuclear signals with Bo18 Ab. C. Absence of immunostaining in the dentate gyrus of a BDV-negative shrew; brain, CL61; D. Abundant immunostaining of olfactory epithelium with presence of strongly stained intranuclear bodies, anti-P antibody, shrew CL73; E. Lack of immunostaining in the olfactory epithelium of a BDV-negative animal, anti-P antibody, shrew CL61; F. Immunostaining of entire bronchial epithelium and underlying smooth muscle layer, lung, anti-P antibody, shrew CL62; G. Immunostaining of a group of glandular epithelial cells, salivary gland, anti-P antibody, shrew CL62; H. Immunostaining of keratinocytes and epithelia of hair follicles, skin; shrew CL62; I. Complete absence of immunostaining in the skin of a BDV-negative animal; anti-P antibody, shrew CL61; J. Immunostaining of myocardial cells; heart; Bo18 Ab; shrew CL76; K. Abundant immunostaining of adipocytes in abdominal fat tissue; anti-P antibody; shrew CL73; L. Complete absence of immunostaining in the fat tissue of a BDV-negative animal; anti-P antibody.
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pone-0093659-g006: Immunohistochemical staining patterns of different organs with the polyclonal anti-P antibody and the monoclonal antibody Bo18.A. Diffuse immunostaining in the area of the dentate gyrus, brain, anti-P antibody; shrew CL72; B. Diffuse immunostaining in the area of the dentate gyrus, brain, Bo18 Ab; Note slightly different immunostaining with presence of nuclear signals with anti-P antibody and absence of nuclear signals with Bo18 Ab. C. Absence of immunostaining in the dentate gyrus of a BDV-negative shrew; brain, CL61; D. Abundant immunostaining of olfactory epithelium with presence of strongly stained intranuclear bodies, anti-P antibody, shrew CL73; E. Lack of immunostaining in the olfactory epithelium of a BDV-negative animal, anti-P antibody, shrew CL61; F. Immunostaining of entire bronchial epithelium and underlying smooth muscle layer, lung, anti-P antibody, shrew CL62; G. Immunostaining of a group of glandular epithelial cells, salivary gland, anti-P antibody, shrew CL62; H. Immunostaining of keratinocytes and epithelia of hair follicles, skin; shrew CL62; I. Complete absence of immunostaining in the skin of a BDV-negative animal; anti-P antibody, shrew CL61; J. Immunostaining of myocardial cells; heart; Bo18 Ab; shrew CL76; K. Abundant immunostaining of adipocytes in abdominal fat tissue; anti-P antibody; shrew CL73; L. Complete absence of immunostaining in the fat tissue of a BDV-negative animal; anti-P antibody.

Mentions: Twelve RT-PCR-positive shrews showed abundant immunostaining. Brain and spinal cord had no infiltration of inflammatory cells and had a diffuse pattern of specific immunoreactivity indicating that all components of central nervous system tissue (neurons, glial cells and their processes) harbored BDV proteins (Figures 6A, 6B). Sometimes the staining intensity was more pronounced within neuronal nuclei and axons. Also sciatic nerves and other peripheral nerves visible in skeletal muscle samples and other tissues were strongly positive. Here the positive signals were strongest within the axons and less distinct within myelin sheaths. Vegetative nerve fibers of different diameters and occasionally vegetative ganglia were clearly positive. Labelled vegetative ganglia were consistently present within the muscle layers of the intestine. Nerve fibers were positive in the dermis and subcutis, in interstitial tissue of salivary glands, pancreas, heart, kidney, liver and lung, in the muscularis, submucosa and propria of the gastrointestinal tract, and in the red pulp of the spleen. A large variety of other tissues were also strongly immunopositive: olfactory epithelium (Figure 6D), bronchial epithelium (Figure 6F), epithelia of salivary glands (Figure 6G), exocrine pancreas, oral cavity including tongue, as well as keratinocytes and hair follicle epithelia of the skin (Figure 6H). Parenchymal cells of the large abdominal organs (liver, kidney) were predominantly negative, with the exception of single hepatocytes. Among mesenchymal tissues, immunostaining was widely positive in smooth muscle cells (gastrointestinal tract, skin, blood vessel walls, bronch(iol)i (Figure 6F), myocardium (Figure 6J), skeletal muscle and fat tissue (Figure 6K). Both antibodies produced comparable staining patterns and intensities. The anti-P-antibody tended to produce a more distinct nuclear staining pattern, while the staining achieved with the Bo18 antibody was more diffuse. The negative controls did not show any immunohistochemical signals (Figures 6C, 6E, 6I, 6L). Two bicolored white-toothed shrews (CL19, CL35) displayed no positive signals in immunohistochemistry despite positivity in BDV RT-PCR.


The bicolored white-toothed shrew Crocidura leucodon (HERMANN 1780) is an indigenous host of mammalian Borna disease virus.

Dürrwald R, Kolodziejek J, Weissenböck H, Nowotny N - PLoS ONE (2014)

Immunohistochemical staining patterns of different organs with the polyclonal anti-P antibody and the monoclonal antibody Bo18.A. Diffuse immunostaining in the area of the dentate gyrus, brain, anti-P antibody; shrew CL72; B. Diffuse immunostaining in the area of the dentate gyrus, brain, Bo18 Ab; Note slightly different immunostaining with presence of nuclear signals with anti-P antibody and absence of nuclear signals with Bo18 Ab. C. Absence of immunostaining in the dentate gyrus of a BDV-negative shrew; brain, CL61; D. Abundant immunostaining of olfactory epithelium with presence of strongly stained intranuclear bodies, anti-P antibody, shrew CL73; E. Lack of immunostaining in the olfactory epithelium of a BDV-negative animal, anti-P antibody, shrew CL61; F. Immunostaining of entire bronchial epithelium and underlying smooth muscle layer, lung, anti-P antibody, shrew CL62; G. Immunostaining of a group of glandular epithelial cells, salivary gland, anti-P antibody, shrew CL62; H. Immunostaining of keratinocytes and epithelia of hair follicles, skin; shrew CL62; I. Complete absence of immunostaining in the skin of a BDV-negative animal; anti-P antibody, shrew CL61; J. Immunostaining of myocardial cells; heart; Bo18 Ab; shrew CL76; K. Abundant immunostaining of adipocytes in abdominal fat tissue; anti-P antibody; shrew CL73; L. Complete absence of immunostaining in the fat tissue of a BDV-negative animal; anti-P antibody.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3974811&req=5

pone-0093659-g006: Immunohistochemical staining patterns of different organs with the polyclonal anti-P antibody and the monoclonal antibody Bo18.A. Diffuse immunostaining in the area of the dentate gyrus, brain, anti-P antibody; shrew CL72; B. Diffuse immunostaining in the area of the dentate gyrus, brain, Bo18 Ab; Note slightly different immunostaining with presence of nuclear signals with anti-P antibody and absence of nuclear signals with Bo18 Ab. C. Absence of immunostaining in the dentate gyrus of a BDV-negative shrew; brain, CL61; D. Abundant immunostaining of olfactory epithelium with presence of strongly stained intranuclear bodies, anti-P antibody, shrew CL73; E. Lack of immunostaining in the olfactory epithelium of a BDV-negative animal, anti-P antibody, shrew CL61; F. Immunostaining of entire bronchial epithelium and underlying smooth muscle layer, lung, anti-P antibody, shrew CL62; G. Immunostaining of a group of glandular epithelial cells, salivary gland, anti-P antibody, shrew CL62; H. Immunostaining of keratinocytes and epithelia of hair follicles, skin; shrew CL62; I. Complete absence of immunostaining in the skin of a BDV-negative animal; anti-P antibody, shrew CL61; J. Immunostaining of myocardial cells; heart; Bo18 Ab; shrew CL76; K. Abundant immunostaining of adipocytes in abdominal fat tissue; anti-P antibody; shrew CL73; L. Complete absence of immunostaining in the fat tissue of a BDV-negative animal; anti-P antibody.
Mentions: Twelve RT-PCR-positive shrews showed abundant immunostaining. Brain and spinal cord had no infiltration of inflammatory cells and had a diffuse pattern of specific immunoreactivity indicating that all components of central nervous system tissue (neurons, glial cells and their processes) harbored BDV proteins (Figures 6A, 6B). Sometimes the staining intensity was more pronounced within neuronal nuclei and axons. Also sciatic nerves and other peripheral nerves visible in skeletal muscle samples and other tissues were strongly positive. Here the positive signals were strongest within the axons and less distinct within myelin sheaths. Vegetative nerve fibers of different diameters and occasionally vegetative ganglia were clearly positive. Labelled vegetative ganglia were consistently present within the muscle layers of the intestine. Nerve fibers were positive in the dermis and subcutis, in interstitial tissue of salivary glands, pancreas, heart, kidney, liver and lung, in the muscularis, submucosa and propria of the gastrointestinal tract, and in the red pulp of the spleen. A large variety of other tissues were also strongly immunopositive: olfactory epithelium (Figure 6D), bronchial epithelium (Figure 6F), epithelia of salivary glands (Figure 6G), exocrine pancreas, oral cavity including tongue, as well as keratinocytes and hair follicle epithelia of the skin (Figure 6H). Parenchymal cells of the large abdominal organs (liver, kidney) were predominantly negative, with the exception of single hepatocytes. Among mesenchymal tissues, immunostaining was widely positive in smooth muscle cells (gastrointestinal tract, skin, blood vessel walls, bronch(iol)i (Figure 6F), myocardium (Figure 6J), skeletal muscle and fat tissue (Figure 6K). Both antibodies produced comparable staining patterns and intensities. The anti-P-antibody tended to produce a more distinct nuclear staining pattern, while the staining achieved with the Bo18 antibody was more diffuse. The negative controls did not show any immunohistochemical signals (Figures 6C, 6E, 6I, 6L). Two bicolored white-toothed shrews (CL19, CL35) displayed no positive signals in immunohistochemistry despite positivity in BDV RT-PCR.

Bottom Line: The search for such a reservoir had been unsuccessful until a few years ago five BDV-infected shrews were found in a BD-endemic area in Switzerland.So far, these data lacked further confirmation.Analyses of behavioral and population features of this shrew species revealed that the bicolored white-toothed shrew may indeed play an important role as an indigenous host of BDV.

View Article: PubMed Central - PubMed

Affiliation: IDT Biologika GmbH (IDT), Dessau-Roβlau, Germany.

ABSTRACT
Borna disease (BD) is a sporadic neurologic disease of horses and sheep caused by mammalian Borna disease virus (BDV). Its unique epidemiological features include: limited occurrence in certain endemic regions of central Europe, yearly varying disease peaks, and a seasonal pattern with higher disease frequencies in spring and a disease nadir in autumn. It is most probably not directly transmitted between horses and sheep. All these features led to the assumption that an indigenous virus reservoir of BDV other than horses and sheep may exist. The search for such a reservoir had been unsuccessful until a few years ago five BDV-infected shrews were found in a BD-endemic area in Switzerland. So far, these data lacked further confirmation. We therefore initiated a study in shrews in endemic areas of Germany. Within five years 107 shrews of five different species were collected. BDV infections were identified in 14 individuals of the species bicolored white-toothed shrew (Crocidura leucodon, HERMANN 1780), all originating from BD-endemic territories. Immunohistological analysis showed widespread distribution of BDV antigen both in the nervous system and in epithelial and mesenchymal tissues without pathological alterations. Large amounts of virus, demonstrated by presence of viral antigen in epithelial cells of the oral cavity and in keratinocytes of the skin, may be a source of infection for natural and spill-over hosts. Genetic analyses reflected a close relationship of the BDV sequences obtained from the shrews with the regional BDV cluster. At one location a high percentage of BDV-positive shrews was identified in four consecutive years, which points towards a self-sustaining infection cycle in bicolored white-toothed shrews. Analyses of behavioral and population features of this shrew species revealed that the bicolored white-toothed shrew may indeed play an important role as an indigenous host of BDV.

Show MeSH
Related in: MedlinePlus