Poster Session PPo3: 
Transmission and Pathogenesis

Abstract

Introduction. Blood transfusion associated vCJD infection has been observed in three codon 129 MM and one MV genotype cases. Passage of the vCJD agent in humans may generate a more infectious strain leading to an increased threat to the population. To understand whether strain adaptation has occurred we inoculated a panel of wild-type and humanised transgenic mice with material from donor and blood recipient vCJD cases.Results. There was evidence of transmission with all inocula except the brain from the MV genotype case that was devoid of TSE pathology. Incubation period data show similarities across all inocula. The lesion profile scores for TSE vacuolation were similar between; donor and recipients, inocula sources, and mouse lines. The presence of PrP-Sc also confirmed similarities between blood donor and recipient vCJD cases.Methods. Transgenic and wild-type mice were inoculated with brain and spleen material from an MM genotype blood transfusion associated vCJD case, the MV blood transfusion associated preclinical vCJD case, and both vCJD blood donors.Conclusions.(1) Spleen tissue from the MV preclinical vCJD blood recipient was transmissible, indicating that MV hosts can propagate the vCJD agent, and that significant levels of infectious agent are present in the spleen before CNS involvement. 'Silent' spread within the human population is therefore a possibility from these carriers. (2) As blood donor and recipient vCJD cases show similar transmission properties from both brain and spleen material we hypothesise that human-to-human infection via this route has not caused adaptation to a more infectious agent. Background. It is widely regarded that individual mouse adapted TSE strains are distinguished based on reproducible incubation periods and vacoulation patterns unique to a specific mouse line by inoculation via a consistent route. To investigate if a change of route of administration can alter the strain properties in the mice we compared TSE transmission properties and strain stability in IM mice following serial titration of mouse adapted BSE (301V) via oral, intragastric (i.g.) and intracerebral (i.c.) routes. Poster Session PPo3: Transmission and Pathogenesis Results.Analysis of lesion profiles demonstrated that the lesion profiles from the i.c. challenges were elevated compared to the i.g and oral routes although area G 1 (medulla) was consistently high irrespective of route of administration. Within the same route of administration lesion profiles seem to be more stable between different dilutions. Mean incubation periods at the 10-1 dilution following oral or i.g. inoculations were prolonged significantly compared to the i.c route (263, 232 and 123 mean days post inoculation respectively).Materials and Methods. Standardised 301V strain was inoculated into IM mice. Post mortem TSE diagnosis was confirmed by microscopy examination of haematoxylin and eosin (H&E) sections. Lesion profiles which are a graphical representation of vacuolar lesion intensity in specific neuroanatomical areas were cons...