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RNA may help convert harmless brain proteins into rogue prions, according to a paper in the 16 October print issue of Nature (Vol. 425, No. 6959, pp. 717-720). A second report, published online, describes how the infectious prion particles may enter the brain. The studies help elucidate the mechanisms behind prion diseases, such as bovine spongiform encephalitis (BSE) and Creutzfeldt-Jakob disease (CJD).
Prion infections are thought to begin when a victim eats contaminated material. Abnormal prion proteins (PrPSc) accumulate and replicate in the lymphoid organs, such as the spleen and lymph nodes, then make their way to the brain. Here, they may trigger the conversion of naturally occurring, harmless prion proteins into PrPSc. RNA may help this process, say Surachai Supattapone and colleagues. When samples of non-infected and infected brain are mixed, levels of PrPSc increase. When RNA is added to the mix, the amplification is boosted further. Although they may appear contradictory, the results may fit with the popular protein-only hypothesis of prion diseases. This theory states that the infectious agent is a protein. "As the authors point out, RNA may be serving as a required host cofactor in PrP conversion rather than an obligatory component of the informational molecule of the transmissible agent," say Byron Caughey and David A. Kocisko in an accompanying News and Views article. Adriano Aguzzi and colleagues describe how PrPSc may enter the brain. The team engineered mice in which prion-rich dendritic cells were abnormally close to the nerve endings in the spleen. The animals developed disease symptoms more quickly than normal mice. This suggests that prions may travel from the lymphoid organs, along splenic neurons and into the central nervous system. Invasion of the brain by infectious prion proteins may be affected by the distance between dendritic cells and the nerve endings in the spleen, the team speculates. CONTACT: Surachai Supattapone
Dartmouth Medical School
Hanover, NH
USA
Tel: +1 603 650 1192 (available from Monday 13 October)
E-mail: supattapone@dartmouth.edu Adriano Aguzzi
University Hospital Zurich
Switzerland
Tel: +41 1 255 2869 / 2107
E-mail: adriano@pathol.unizh.ch Byron Caughey
NIAID/NIH Rocky Mountain Labs
Hamilton, MT
USA
Tel: +1 406 363 3211 ext. 264
E-mail: BCAUGHEY@niaid.nih.gov (C) Nature press release.
Message posted by: Trevor M. D'Souza
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