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Persistent retroviral infection with MoMuLV influences neuropathological signature and phenotype of prion disease

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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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Acknowledgments

We thank U. Mueller, S. Deutsch, and the mouse pathology core facility of the UKE for technical assistance. This work is supported by grants of the Deutsche Forschungsgemeinschaft (FOR885 and GRK1459 to M.G.), the Landesexzellenzinitiative of Hamburg (SDI-LEXI) to M.G. and a pro-exzellenzia grant (city of Hamburg) and the BMBF-grant 01GZ0712 to S.K.

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  1. Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Susanne Krasemann, Melanie Neumann, Jan-Paul Luepke, Juliane Grashorn, Steffanie Wurr & Markus Glatzel

  2. Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany

    Carol Stocking

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  1. Susanne Krasemann
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Correspondence to Markus Glatzel.

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J.-P. Luepke: Deceased.

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Krasemann, S., Neumann, M., Luepke, JP. et al. Persistent retroviral infection with MoMuLV influences neuropathological signature and phenotype of prion disease. Acta Neuropathol 124, 111–126 (2012). https://doi.org/10.1007/s00401-012-0944-1

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