RT Journal Article
SR Electronic
T1 Prion infection, transmission, and cytopathology modeled in a low-biohazard human cell line
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000814
DO 10.26508/lsa.202000814
VO 3
IS 8
A1 Merve Avar
A1 Daniel Heinzer
A1 Nicolas Steinke
A1 Berre Doğançay
A1 Rita Moos
A1 Severine Lugan
A1 Claudia Cosenza
A1 Simone Hornemann
A1 Olivier Andréoletti
A1 Adriano Aguzzi
YR 2020
UL https://www.life-science-alliance.org/content/3/8/e202000814.abstract
AB Transmission of prion infectivity to susceptible murine cell lines has simplified prion titration assays and has greatly reduced the need for animal experimentation. However, murine cell models suffer from technical and biological constraints. Human cell lines might be more useful, but they are much more biohazardous and are often poorly infectible. Here, we describe the human clonal cell line hovS, which lacks the human PRNP gene and expresses instead the ovine PRNP VRQ allele. HovS cells were highly susceptible to the PG127 strain of sheep-derived murine prions, reaching up to 90% infected cells in any given culture and were maintained in a continuous infected state for at least 14 passages. Infected hovS cells produced proteinase K–resistant prion protein (PrPSc), pelletable PrP aggregates, and bona fide infectious prions capable of infecting further generations of naïve hovS cells and mice expressing the VRQ allelic variant of ovine PrPC. Infection in hovS led to prominent cytopathic vacuolation akin to the spongiform changes observed in individuals suffering from prion diseases. In addition to expanding the toolbox for prion research to human experimental genetics, the hovS cell line provides a human-derived system that does not require human prions. Hence, the manipulation of scrapie-infected hovS cells may present fewer biosafety hazards than that of genuine human prions.