Cell cultures can sort out CJD and scrapie infectious agents

10/19/05



Caption: Noriyuki Nishida and Laura Manuelidis
Click here for a high resolution photograph.

New Haven, Conn. – Research in Japan and at Yale University School of Medicine shows that infection with a weak strain of Creutzfeldt-Jacob Disease (CJD) prevents infection by more virulent strains and that the protection requires persistent replication by the infectious agent, but not misfolded prions.

The "prion diseases" including Mad Cow Disease, scrapie and CJD have been in recent news because of their devastating effects on the brain and concern about transmission of the infectious agents. In prior research on animals, a weaker strain of CJD protected against a more destructive strain.

This study, reported in the journal Science, duplicated and extended results of the animal experiments in a neural cell culture assay. In culture assays it was possible to test human and sheep agent strain combinations that could not be discriminated in animals. These studies showed that a persistent protective CJD infection did not require cells from the immune system or misfolded prions. Cells infected with a weak strain of CJD were also protected from infection by two strains of sheep scrapie agent.

"We demonstrate a new and very sensitive assay for infection by these agents that can discriminate among different strains, such as those that cause sheep scrapie and human CJD," said senior author Laura Manuelidis, professor and section chief of Surgery/Neuropathology at Yale.

According to Manuelidis protection with a weak animal agent may account for the low incidence of CJD linked to Mad Cow Disease in people. "Our plan is to use these rapid infectivity assays to identify the different agents -- including those linked to Mad Cow Disease -- on the molecular as well as biological levels," said Manuelidis.

"This, as well as our previous results showing that most of the abnormal prion protein can be separated from infectious particles, point to a virus as the causal agent." said Manuelidis "These results are not consistent with the idea that abnormal forms of the prion protein are infectious."

Source: Eurekalert & others

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