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

• Published in: Acta neuropathologica Vol. 124; no. 1; pp. 111 - 126
• Main Authors: Krasemann, Susanne, Neumann, Melanie, Luepke, Jan-Paul, Grashorn, Juliane, Wurr, Steffanie, Stocking, Carol, Glatzel, Markus
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.07.2012; Springer; Springer Nature B.V
• Subjects: Animal models; Animals; Astrocytes; Brain; Cell Line, Transformed; Central nervous system; Central Nervous System - pathology; Central Nervous System - virology; Dendritic Cells - pathology; Disease; Disease Models, Animal; Disease transmission; DNA-Binding Proteins - metabolism; Ethylenediaminetetraacetic acid; Genotype & phenotype; Glial Fibrillary Acidic Protein - metabolism; Gliosis; Health aspects; Humans; Infection; Infections; Infectivity; Kinetics; Laboratory animals; Leukemia; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Mice; Moloney murine leukemia virus - pathogenicity; Nervous system; Neuropathology; Neurosciences; Original Paper; Pathogens; Pathology; Pathophysiology; Phenotype; Prion Diseases - complications; Prion Diseases - metabolism; Prion Diseases - pathology; Prion protein; Prions; Prions - metabolism; Proteins; Retroviridae Infections - complications; Retroviridae Infections - pathology; Retrovirus; Spleen - metabolism; Spleen - pathology; Time Factors; Tumor Virus Infections - complications; Tumor Virus Infections - pathology; Viral infections; Virus diseases; Viruses; Germany; Retrovirus; Prion disease; MoMuLV; Disease phenotype; Neuropathological signature; Prions; Dementia
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s00401-012-0944-1

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.