Co-Infection with the Friend Retrovirus and Mouse Scrapie Does Not Alter Prion Disease Pathogenesis in Susceptible Mice

Pascal Leblanc,Andrew Timmes,Sandrine Alais,Sue Priola,Lara Myers,Anne Ward,Kim Hasenkrug,Ronald J Messer,Jiyan Ma

doi:10.1371/journal.pone.0030872

Abstract

Prion diseases are fatal, transmissible neurodegenerative diseases of the central nervous system. An abnormally protease-resistant and insoluble form (PrPSc) of the normally soluble protease-sensitive host prion protein (PrPC) is the major component of the infectious prion. During the course of prion disease, PrPSc accumulates primarily in the lymphoreticular and central nervous systems. Recent studies have shown that co-infection of prion-infected fibroblast cells with the Moloney murine leukemia virus (Mo-MuLV) strongly enhanced the release and spread of scrapie infectivity in cell culture, suggesting that retroviral coinfection might significantly influence prion spread and disease incubation times in vivo. We now show that another retrovirus, the murine leukemia virus Friend (F-MuLV), also enhanced the release and spread of scrapie infectivity in cell culture. However, peripheral co-infection of mice with both Friend virus and the mouse scrapie strain 22L did not alter scrapie disease incubation times, the levels of PrPSc in the brain or spleen, or the distribution of pathological lesions in the brain. Thus, retroviral co-infection does not necessarily alter prion disease pathogenesis in vivo, most likely because of different cell-specific sites of replication for scrapie and F-MuLV.

Highlights

Prion diseases, known as transmissible spongiform encephalopathies (TSEs), are fatal, neurodegenerative diseases that include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and chronic wasting disease in deer and elk
In the current study we show that, to Moloney murine leukemia virus (Mo-MuLV), coinfection of mouse scrapie-infected tissue cells with Friend murine leukemia virus (F-MuLV) leads to an increase in exosomes, prion protein and scrapie infectivity in vitro
Our results show that retroviral co-infection does not necessarily alter prion disease pathogenesis in vivo

Summary

Introduction

Known as transmissible spongiform encephalopathies (TSEs), are fatal, neurodegenerative diseases that include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and chronic wasting disease in deer and elk. PrPC is a cell-surface glycoprotein expressed in various mammalian tissues including brain, spinal cord, nerve, heart, muscle, spleen and lymph node (for review see [3]). Even though the major pathological hallmarks of prion disease are spongiform degeneration and gliosis in the brain, prion infection and the conversion of PrPC to PrPSc are not necessarily restricted to brain areas but can occur in peripheral lymphoid tissues such as spleen and lymph nodes [4]. The conversion of PrPC to PrPSc [5] and the spread of the prion agent from peripheral sites of infection to the brain and vice versa [4,6,7,8,9,10] are key events in the pathogenesis of prion diseases. Chronic inflammatory conditions such as nephritis, hepatitis or mastitis can lead to changes in the distribution of scrapie infectivity in the organism the mechanisms involved are poorly understood [11,12,13]

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