Persistent retroviral infection with MoMuLV influences neuropathological signature and phenotype of prion disease.
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Persistent retroviral infection with MoMuLV influences neuropathological signature and phenotype of prion disease. / Krasemann, Susanne; Neumann, Melanie; Luepke, Jan-Paul; Grashorn, Juliane; Wurr, Steffanie; Stocking, Carol; Glatzel, Markus.
In: ACTA NEUROPATHOL, Vol. 124, No. 1, 1, 2012, p. 111-126.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Persistent retroviral infection with MoMuLV influences neuropathological signature and phenotype of prion disease.
AU - Krasemann, Susanne
AU - Neumann, Melanie
AU - Luepke, Jan-Paul
AU - Grashorn, Juliane
AU - Wurr, Steffanie
AU - Stocking, Carol
AU - Glatzel, Markus
PY - 2012
Y1 - 2012
N2 - A fundamental step in pathophysiology of prion diseases is the conversion of the host encoded prion protein (PrP(C)) into a misfolded isoform (PrP(Sc)) that accumulates mainly in neuronal but also non-neuronal tissues. Prion diseases are transmissible within and between species. In a subset of prion diseases, peripheral prion uptake and subsequent transport to the central nervous system are key to disease initiation. The involvement of retroviruses in this process has been postulated based on the findings that retroviral infections enhance the spread of prion infectivity and PrP(Sc) from cell to cell in vitro. To study whether retroviral infection influences the phenotype of prion disease or the spread of prion infectivity and PrP(Sc) in vivo, we developed a murine model with persistent Moloney murine leukemia retrovirus (MoMuLV) infection with and without additional prion infection. We investigated the pathophysiology of prion disease in MoMuLV and prion-infected mice, monitoring temporal kinetics of PrP(Sc) spread and prion infectivity, as well as clinical presentation. Unexpectedly, infection of MoMuLV challenged mice with prions did not change incubation time to clinical prion disease. However, clinical presentation of prion disease was altered in mice infected with both pathogens. This was paralleled by remarkably enhanced astrogliosis and pathognomonic astrocyte morphology in the brain of these mice. Therefore, we conclude that persistent viral infection might act as a disease modifier in prion disease.
AB - A fundamental step in pathophysiology of prion diseases is the conversion of the host encoded prion protein (PrP(C)) into a misfolded isoform (PrP(Sc)) that accumulates mainly in neuronal but also non-neuronal tissues. Prion diseases are transmissible within and between species. In a subset of prion diseases, peripheral prion uptake and subsequent transport to the central nervous system are key to disease initiation. The involvement of retroviruses in this process has been postulated based on the findings that retroviral infections enhance the spread of prion infectivity and PrP(Sc) from cell to cell in vitro. To study whether retroviral infection influences the phenotype of prion disease or the spread of prion infectivity and PrP(Sc) in vivo, we developed a murine model with persistent Moloney murine leukemia retrovirus (MoMuLV) infection with and without additional prion infection. We investigated the pathophysiology of prion disease in MoMuLV and prion-infected mice, monitoring temporal kinetics of PrP(Sc) spread and prion infectivity, as well as clinical presentation. Unexpectedly, infection of MoMuLV challenged mice with prions did not change incubation time to clinical prion disease. However, clinical presentation of prion disease was altered in mice infected with both pathogens. This was paralleled by remarkably enhanced astrogliosis and pathognomonic astrocyte morphology in the brain of these mice. Therefore, we conclude that persistent viral infection might act as a disease modifier in prion disease.
KW - Animals
KW - Humans
KW - Time Factors
KW - Disease Models, Animal
KW - Mice
KW - Phenotype
KW - Glial Fibrillary Acidic Protein/metabolism
KW - DNA-Binding Proteins/metabolism
KW - Cell Line, Transformed
KW - Central Nervous System/pathology/virology
KW - Dendritic Cells/pathology
KW - Moloney murine leukemia virus/pathogenicity
KW - Prion Diseases/complications/metabolism/pathology
KW - Prions/metabolism
KW - Retroviridae Infections/complications/pathology
KW - Spleen/metabolism/pathology
KW - Tumor Virus Infections/complications/pathology
KW - Animals
KW - Humans
KW - Time Factors
KW - Disease Models, Animal
KW - Mice
KW - Phenotype
KW - Glial Fibrillary Acidic Protein/metabolism
KW - DNA-Binding Proteins/metabolism
KW - Cell Line, Transformed
KW - Central Nervous System/pathology/virology
KW - Dendritic Cells/pathology
KW - Moloney murine leukemia virus/pathogenicity
KW - Prion Diseases/complications/metabolism/pathology
KW - Prions/metabolism
KW - Retroviridae Infections/complications/pathology
KW - Spleen/metabolism/pathology
KW - Tumor Virus Infections/complications/pathology
M3 - SCORING: Journal article
VL - 124
SP - 111
EP - 126
JO - ACTA NEUROPATHOL
JF - ACTA NEUROPATHOL
SN - 0001-6322
IS - 1
M1 - 1
ER -
