Subviral Agents

1. Subviral Agents Satellites and viroids – parasites of parasites! Prions - infectious protein molecules Principles of Molecular Virology

2. Satellites Small RNA molecules dependent on the presence of another virus for multiplication Approximately 500 to 2000 nucleotides of single-stranded RNA Little or no nucleotide sequence similarity between the satellite and the helper virus genome Cause distinct disease symptoms in plants that are not seen with the helper virus alone Replication of satellites usually interferes with the replication of the helper virus Principles of Molecular Virology

3. Viroids Very small (200- to 400-nt) rod-like RNA molecules Principles of Molecular Virology

4. Hepatitis delta virus (HDV) Chimeric molecule with some of the properties of a satellite virus and some of a viroid Principles of Molecular Virology

5. Prions Transmissible, chronic, progressive infections of the nervous system Pathology is similar to that of amyloid diseases such as Alzheimer’s syndrome, to distinguish them they are known as transmissible spongiform encephalopathies (TSE) Originally thought to be caused by viruses, doubts arose in the 1960s 1982 - Stanley Prusiner coined the term prion (proteinaceous infectious particle) Principles of Molecular Virology

6. Pathology of Prion Diseases Similar underlying pathology: Deposition of abnormal protein deposits in various organs ("amyloid") Spongiform encephalopathies - characteristic holes in thin sections of affected brain tissue Principles of Molecular Virology

7. TSE in Animals Scrapie Transmissible Mink Encephalopathy (TME) Feline Spongiform Encephalopathy (FSE) Chronic Wasting Disease (CWD) Principles of Molecular Virology

8. Bovine Spongiform Encephalopathy (BSE) Principles of Molecular Virology

9. Human TSEs Sporadic - Creutzfeldt–Jakob disease (CJD) Iatrogenic/acquired TSE (neurosurgery, transplantation) Familial (inherited) vCJD (from BSE) Principles of Molecular Virology

10. Molecular Biology of Prions Resistance to heat inactivation Resistance to radiation damage Resistance to DNAse and RNAse treatment Sensitivity to urea, SDS, phenol, other protein-denaturing chemicals Principles of Molecular Virology

11. PrP Principles of Molecular Virology

12. Prion species barrier Principles of Molecular Virology

13. PrPC and PrPSc Principles of Molecular Virology

14. Summary Several types of non-viral, subcellular pathogens have disease-causing potential: Satellites Viroids Prions Conventional strategies to combat virus infections (drugs and vaccines) have no effect on these unconventional agents Principles of Molecular Virology

15. Further Reading Alpers, M.P. (2008) Review. The epidemiology of kuru: monitoring the epidemic from its peak to its end. Philos Trans R Soc Lond B Biol Sci. 363(1510): 3707-3713 Ding, B. (2009) The biology of viroid-host interactions. Ann Rev Phytopathol. 47: 105-131 Dodds, J.A. (1998) Satellite tobacco mosaic virus. Annual Review of Phytopathology, 36: 295–310 Klitzman, R. (1998) The Trembling Mountain: A Personal Account of Kuru, Cannibals, and Mad Cow Disease. Plenum Press, New York. ISBN 030645792X Sigurdson, C.J. (2008) A prion disease of cervids: chronic wasting disease. Vet Res. 39(4): 41 Tabler, M. and Tsagris, M. (2004). Viroids: petite RNA pathogens with distinguished talents. Trends in Plant Science, 9: 339–348 Tseng, C.H. and Lai, M.C.C. (2009) Hepatitis Delta Virus RNA Replication. Viruses 1(3): 818-831. Tuite, M.F. and Serio, T.R. (2010) The prion hypothesis: from biological anomaly to basic regulatory mechanism. Nat Rev Mol Cell Biol. 11(12): 823-833 Watts, J.C., Balachandran, A. and Westaway, D. (2006) The Expanding Universe of Prion Diseases. PLoS Pathog 2(3): e26 Wadsworth, J.D. and Collinge, J. (2007) Update on human prion disease. Biochim Biophys Acta. 1772(6): 598-609 Principles of Molecular Virology