Successive passaging of the scrapie strains, ME7-ha and 139A-ha, generated by the interspecies transmission of mouse-adapted strains into hamsters markedly shortens the incubation times, but maintains their molecular and pathological properties

Abstract

As a type of zoonotic disease, prion diseases may be transmitted naturally and experimentally among species. In a previous study, we demonstrated that the mouse-adapted scrapie strains, ME7 (ME7-mo) and 139A (139A-mo), can overcome the species barrier and induce experimental scrapie when inoculated into Golden hamsters and generated 2 new hamster-adapted strains, ME7 (ME7-ha) and 139A (139A-ha). In the present study, in order to assess the infectivity and other molecular and neuropathological properties of the newly formed scrapie agents, ME7-ha and 139A-ha were further intracerebrally inoculated into hamsters. Compared with infection with 1st passage strains, the incubation times and clinical courses of infection with 2nd passage strains were markedly shorter, which were quite comparable with those of the mice infected with their parent mouse strains. The glycosylation patterns of brain PrP(Sc) in the animals infected with the 2nd passage of those 2 strains maintained similar features as those in the animals infected with the 1st passage of those strains, with predominantly diglycosylated PrP(Sc). Neuropathological assays revealed comparable spongiform degeneration and microglia proliferation in the brain tissues from the infected mice and hamsters, but markedly more plaque-like deposits of PrP(Sc) and more severe astrogliosis in the brains of the hamster. These data indicate that the strains, ME7-ha 1st and 139A-ha 1st generated by interspecies infection can passage in the new host hamster and stably maintain their molecular and neuropathological characteristics.

Re-infection of the prion from the scrapie-infected cell line SMB-S15 in three strains of mice, CD1, C57BL/6 and Balb/c

“…Furthermore, as demonstrated in the present study, the incubation times of the second passages of all infected mice were shorter than the first passages. It has been previously observed, when the TSE agents are passaged in new, sensitive host species, that the incubation period will shorten during the first passage and become stable in the later passages ( 24 ). Although SMB cells are mouse neuron-derived cells, the relatively shorter incubation times of the second passages of S15-infected mice noted in the present study indicate that the scrapie agents propagating in the cultured cells in vitro need to adapt a little when replicating in the brain tissues of the same species in vivo .…”

“…Furthermore, the neuropathological features, such as PrP Sc deposits, spongiform degeneration, reactive gliosis and activated microglia, are also similar in the three types of infected mice. However, the molecular profiles of PrP Sc and some neuropathological features change during interspecies transmission and were maintained stably afterwards ( 24 ). This implies that prions possess stable pathogenic and pathological features when they adapt in a particular species, regardless of whether they propagate in vivo or in vitro .…”

MiRNA expression profiles in the brains of mice infected with scrapie agents 139A, ME7 and S15

“…17 However, they exhibit different incubation times in the interspecies infection from mouse to hamster, where ME7 shows a longer incubation time, although their incubation periods become quite comparable with subsequent passages. 18 The brain proteomic assays from our group have recently identified a larger number of differentially expressed proteins in ME7-infected mice (Shi et al unpublished data). Coincidental with the observations from the proteomics analyses, ME7-infected mice contain more significantly changed brain miRNAs than 139A-infected mice.…”

Light and electron microscopic studies of the 139A-H strain of scrapie passaged in hamsters

“…The topography of deposition of PrP Sc revealed marked differences from region to region; the highest signal was observed in the CA2-molecular layer, CA1-pyramidal and entorhinal cortex. There are no data available to make a comparison [31]. The electron microscopy revealed extensive autophagy and, to a lesser degree, apoptosis.…”