“Protein insight into spread of vCJD to brain,” BBC News (2011)

http://www.bbc.co.uk/news/uk-scotland-edinburgh-east-fife-15988283

Scientists have discovered that blocking the production of proteins in the immune system could prevent the spread of a disease that destroys nerve cells.

Researchers at Edinburgh University’s Roslin Institute said vCJD occurs when proteins known as prions accumulate in the spleen, lymph nodes and tonsils.

They then spread to the brain, causing a disease that can destroy nerve cells.

The study could lead to treatments to stop vCJD spreading to the brain.

The team said a study showed that blocking the production of a protein, PrPC, in one type of immune cell could stop the spread of prions.

Stopping these cells from expressing this protein did not affect the regular function of the immune system, they said.

The researchers found that when the follicular dendritic cells expressed PrPC, prions were able to replicate on the surface of these cells and spread throughout the body.

However, when the cells were prevented from producing PrPC, the prions were not able to multiply and were destroyed by other cells in the immune system.

The study, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), has been published in the PLoS Pathogens journal.

Scientists said that any treatments would only be viable if the condition was diagnosed in its early stages.

 

“Follicular dendritic cell-specific prion protein (PrPc) expression alone is sufficient to sustain prion infection in the spleen,” McCulloch et al., PLoS Pathogens (2011)

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002402

Following peripheral exposure high levels of prion-specific PrPSc accumulate first upon follicular dendritic cells (FDC) in lymphoid tissues before spreading to the CNS. Expression of PrPC is mandatory for cells to sustain prion infection and FDC appear to express high levels. However, whether FDC actively replicate prions or simply acquire them from other infected cells is uncertain. In the attempts to-date to establish the role of FDC in prion pathogenesis it was not possible to dissociate the Prnp expression of FDC from that of the nervous system and all other non-haematopoietic lineages. This is important as FDC may simply acquire prions after synthesis by other infected cells. To establish the role of FDC in prion pathogenesis transgenic mice were created in which PrPC expression was specifically “switched on” or “off” only on FDC. We show that PrPC-expression only on FDC is sufficient to sustain prion replication in the spleen. Furthermore, prion replication is blocked in the spleen when PrPC-expression is specifically ablated only on FDC. These data definitively demonstrate that FDC are the essential sites of prion replication in lymphoid tissues. The demonstration that Prnp-ablation only on FDC blocked splenic prion accumulation without apparent consequences for FDC status represents a novel opportunity to prevent neuroinvasion by modulation of PrPC expression on FDC.