Similarly, there was no difference between the two groups of mice in the amount of PrPSc present in the brain. These results are consistent with the similar Orbifloxacin disease incubation times observed for mice infected with 22L alone or mice infected with both 22L and FV and suggest that FV co-infection does not lead to an increased accumulation of PrPSc during mouse scrapie infection. While replication of FV in the spleen did not appear to increase the level of PrPSc in the spleen, it was possible that the distribution of PrPSc was altered. Spleens from three mice infected either with 22L plus FV, 22L alone, or FV alone were stained with the antiPrP antibody D13 and the distribution of PrPSc analyzed. Representative results are shown in Figure 4. In F1 mice inoculated with 22L alone, punctate deposits of PrPSc were found primarily in the white pulp in a pattern consistent with deposition in follicular dendritic cells. A similar pattern of PrPSc deposition was found in mice co-infected with 22L and FV, suggesting that FV co-infection did not lead to a change in PrPSc distribution in the spleen. Although retroviral co-infection did not affect either scrapie disease incubation times or PrPSc Atropine sulfate levels at the clinical stage of disease, it could have affected the pathology induced by scrapie infection in the brain. The major pathological hallmark of the 22L strain of mouse scrapie is extensive vacuolation in the cerebellum. In order to determine whether or not there was a difference in cerebellar vacuolation in F1 mice co-infected with 22L and FV, the extent of vacuolation in the brains of three coinfected mice, 22L infected mice, or FV infected mice were analyzed. Representative results are shown in Figure 5. When compared to mice infected with 22L scrapie alone, no difference was seen in the extent or localization of vacuolation in the cerebellum or other regions of the brain of mice co-infected with 22L and FV. Similarly, no differences in the distribution of PrPSc were observed in the cerebellum or other brains areas between control mice infected with 22L alone and mice coinfected with 22L and FV. Thus, retroviral co-infection of 22L scrapie-infected mice did not noticeably alter the pathology of 22L scrapie in the brain. One possible explanation for the lack of effect from co-infection with Friend retrovirus was that prion infection and retroviral infection occurred in separate cell populations. Prion replication in the spleen occurs primarily in follicular dendritic cells and can be detected as early as 1 week post-infection. FV is a gamma retrovirus that requires actively dividing cells for replication but its replication specifically in FDCs has not been investigated. In order to determine if FV infected spleen FDCs during the acute stage of infection, mice were inoculated i.v. with FV and the spleens harvested around the time of peak FV replication 7 days later.