Persistent retroviral infection with MoMuLV influences neuropathological signature and phenotype of prion disease |
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Authors: | Susanne Krasemann Melanie Neumann Jan-Paul Luepke Juliane Grashorn Steffanie Wurr Carol Stocking Markus Glatzel |
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Institution: | (1) Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany;(2) Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany; |
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Abstract: | A fundamental step in pathophysiology of prion diseases is the conversion of the host encoded prion protein (PrPC) into a misfolded isoform (PrPSc) 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 PrPSc from cell to cell in vitro. To study whether retroviral infection influences the phenotype of prion disease or the spread
of prion infectivity and PrPSc 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 PrPSc 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. |
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