Prion infectivity in variant Creutzfeldt-Jakob disease rectum

Abstract

Background: Disease-related prion protein (PrPSc) is readily detectable in lymphoreticular tissues in variant Creutzfeldt-Jakob disease (vCJD), but not in other forms of human prion disease. This distinctive pathogenesis, with the unknown population prevalence of asymptomatic vCJD infection, has led to significant concerns that secondary transmission of vCJD prions will occur through a wide range of surgical procedures. To date PrP Sc:prion infectivity ratios have not been determined in vCJD, and it is unknown whether vCJD prions are similar to experimental rodent prions, where PrPSc concentration typically reflects infectious prion titre. Aim: To investigate prion infectivity in vCJD tissue containing barely detectable levels of PrPSc. Methods: Transgenic mice expressing only human PrP (Tg(HuPrP129M+/+ Prnp0/0)-35 and Tg(HuPrP129M +/+ Prnp0/0)-45 mice) were inoculated with brain or rectal tissue from a previously characterised patient with vCJD. These tissues contain the maximum and minimum levels of detectable PrPSc that have been observed in vCJD. Results: Efficient transmission of prion infection was observed in transgenic mice inoculated with vCJD rectal tissue containing PrPSc at a concentration of 104.7-fold lower than that in vCJD brain. Conclusions: These data confirm the potential risks for secondary transmission of vCJD prions via gastrointestinal procedures and support the use of PrPSc as a quantitative marker of prion infectivity in vCJD tissues.