Infectivity in extraneural tissues following intraocular scrapie infection

Intraocular (i.o.) infection of mice with scrapie produces strain-specific targeting of replication and subsequent pathology within the visual system projection areas in the CNS, but also initiates an extraneural infection. Following i.o. infection with ME7 scrapie, infectivity was detected 24 h later in the Harderian gland, the superficial cervical lymph nodes (SCLNs) and the spleen, but not until 20 days in Peyer's patches and inguinal lymph nodes (ILNs). Persistent low levels of infectivity were found in the Harderian gland (which lies within the orbit), but the presence of PrP could not be confirmed by immunolabelling or Western blotting. SCLNs contained maximal amounts of infectivity by 20 days post-infection and remained at this level throughout the incubation period. ILNs reached a similar plateau at 60 days, as did Peyer's patches at 80 days and spleen at 100 days. Further investigation of the role of the spleen in pathogenesis showed that in contrast to ME7 scrapie, mice infected with 79A scrapie had high levels of infectivity in the spleen by 20 days post-infection, irrespective of the route of infection. In addition, the disease developed more rapidly following direct intrasplenic infection with ME7 scrapie than with intraperitoneal infection. Splenectomy at 7 days either before or after i.o. infection had no effect on the incubation period. These results indicate that the rate of replication of infectivity is both tissue and scrapie-strain dependent, and that extraneural spread of infection can occur via the lymphatic system.