A cell line infectible by prion strains from different species

Abstract

It has been shown previously that ovine prion protein (PrP C ) renders rabbit epithelial RK13 cells permissive to the multiplication of ovine prions, thus providing evidence that species barriers can be crossed in cultured cells through the expression of a relevant PrP C . The present study significantly extended this observation by showing that mouse and bank vole prions can be propagated in RK13 cells that express the corresponding PrP C . Importantly, the respective molecular patterns of abnormal PrP (PrP res ) and, where examined, the neuropathological features of the infecting strains appeared to be maintained during the propagation in cell culture. These findings indicate that RK13 cells can be genetically engineered to replicate prion strains faithfully from different species. Such an approach may facilitate investigations of the molecular basis of strain identity and prion diversity.

Cell models of prion infection

“…This was taken by some investigators as an indication that abnormal PrP does not encode the strain characteristics [5]. Interestingly and importantly, although brain-and cell-derived PrP res are different, strain-specific banding pattern differences observed for brain PrP res were also detected after serial propagation in cultured cells [4,13,33,61]. All these findings demonstrate that different prion strains can propagate in a single cell type, indicating that multiplication in different brain cells is not necessary for prion diversity.…”

“…Incubation times, brain vacuolisation, and clinical signs of several murine strains (22F, Chandler, Fukuoka, and SY) remain unchanged following multiplication in N2a, GT1 or SMB cell lines [4,5,13]. Biological characterisation of sheep, mouse, and vole strains of prions propagated in RK13 cells expressing the ovine, murine or vole PrP C , respectively, suggests that these strains are not modified through multiplication in nonneuronal cells as well [33]. In the absence of nucleic acids, strain biological properties are proposed to be encoded by the abnormal PrP [150].…”

“…L929 mouse fibroblasts propagate 22L, ME7, and RML while MG20 microglial cultures can be infected by ME7 and Chandler strains and by the mouse-adapted BSE agent. RK13 cells expressing mouse PrP C are susceptible to several murine prion strains as well [33]. However, there is also evidence that prion multiplication show cell tropism ex vivo.…”

“…RK13 cells, which express no detectable endogenous rabbit PrP C , can be transfected with sheep PrP C and become susceptible to sheep scrapie agent multiplication [146]. The fact that RK13 cells expressing rodent PrP C are also permissive to several rodent-adapted prion strains [33] is a significant step towards obtaining a versatile cell model of prion infection. A further advance has recently been achieved by showing that transduced expression of mouse PrP C conferred prion permissiveness to a hippocampal cell line (HpL3-4) derived from a PrP C knock-out mouse [80].…”

A transfectant RK13 cell line permissive to classical caprine scrapie prion propagation

“…The susceptibility of RK13-based transfectants to corresponding rodent-and cervid-derived prion propagation has been reported. [13][14][15] In this study, we demonstrate for the first time that RK13 cells stably expressing caprine PrP C (cpRK13) was permissive to certain classical caprine scrapie prion isolates prepared from the brain tissues of scrapie-infected goats and ovinized transgenic mice.…”