title: Persistent retroviral infection with MoMuLV influences neuropathological signature and phenotype of prion disease.
abstract: 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.
authors.affiliation: Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Krasemann
authors.forename: Melanie
authors.initials: M
authors.lastname: Neumann
authors.forename: Jan-Paul
authors.initials: JP
authors.lastname: Luepke
authors.forename: Juliane
authors.initials: J
authors.lastname: Grashorn
authors.forename: Steffanie
authors.initials: S
authors.lastname: Wurr
authors.forename: Carol
authors.initials: C
authors.lastname: Stocking
authors.forename: Markus
authors.initials: M
authors.lastname: Glatzel
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D002461:Cell Line, Transformed; D002490:Central Nervous System / Q000473:pathology* / Q000821:virology; D004268:DNA-Binding Proteins / Q000378:metabolism; D003713:Dendritic Cells / Q000473:pathology; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins; D008979:Moloney murine leukemia virus / Q000472:pathogenicity*; D010641:Phenotype; D017096:Prion Diseases / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D011328:Prions / Q000378:metabolism*; D012192:Retroviridae Infections / Q000150:complications / Q000473:pathology*; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014412:Tumor Virus Infections / Q000150:complications / Q000473:pathology*
chemical_list: C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D011328:Prions