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Subviral Agents • Satellites and viroids – parasites of parasites! • Prions - infectious Subviral Agents • Satellites and viroids – parasites of parasites! • Prions - infectious protein molecules Principles of Molecular Virology © Elsevier, 2011.

Satellites • Small RNA molecules dependent on the presence of another virus for multiplication 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 © Elsevier, 2011.

Viroids Very small (200 - to 400 -nt) rod-like RNA molecules Principles of Molecular Viroids Very small (200 - to 400 -nt) rod-like RNA molecules Principles of Molecular Virology © Elsevier, 2011.

Hepatitis delta virus (HDV) Chimeric molecule with some of the properties of a satellite Hepatitis delta virus (HDV) Chimeric molecule with some of the properties of a satellite virus and some of a viroid Principles of Molecular Virology © Elsevier, 2011.

Prions • Transmissible, chronic, progressive infections of the nervous system • Pathology is similar 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 1960 s • 1982 - Stanley Prusiner coined the term prion (proteinaceous infectious particle) Principles of Molecular Virology © Elsevier, 2011.

Pathology of Prion Diseases Similar underlying pathology: • Deposition of abnormal protein deposits in 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 © Elsevier, 2011.

TSE in Animals • Scrapie • Transmissible Mink Encephalopathy (TME) • Feline Spongiform Encephalopathy TSE in Animals • Scrapie • Transmissible Mink Encephalopathy (TME) • Feline Spongiform Encephalopathy (FSE) • Chronic Wasting Disease (CWD) Principles of Molecular Virology © Elsevier, 2011.

Bovine Spongiform Encephalopathy (BSE) Principles of Molecular Virology © Elsevier, 2011. Bovine Spongiform Encephalopathy (BSE) Principles of Molecular Virology © Elsevier, 2011.

Human TSEs • • Sporadic - Creutzfeldt–Jakob disease (CJD) Iatrogenic/acquired TSE (neurosurgery, transplantation) Familial Human TSEs • • Sporadic - Creutzfeldt–Jakob disease (CJD) Iatrogenic/acquired TSE (neurosurgery, transplantation) Familial (inherited) v. CJD (from BSE) Principles of Molecular Virology © Elsevier, 2011.

Molecular Biology of Prions • • Resistance to heat inactivation Resistance to radiation damage 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 © Elsevier, 2011.

Pr. P Principles of Molecular Virology © Elsevier, 2011. Pr. P Principles of Molecular Virology © Elsevier, 2011.

Prion species barrier Principles of Molecular Virology © Elsevier, 2011. Prion species barrier Principles of Molecular Virology © Elsevier, 2011.

Pr. PC and Pr. PSc Principles of Molecular Virology © Elsevier, 2011. Pr. PC and Pr. PSc Principles of Molecular Virology © Elsevier, 2011.

Summary Several types of non-viral, subcellular pathogens have disease-causing potential: • Satellites • Viroids 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 © Elsevier, 2011.

Further Reading Alpers, M. P. (2008) Review. The epidemiology of kuru: monitoring the epidemic 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 030645792 X 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. PLo. S Pathog 2(3): e 26 Wadsworth, J. D. and Collinge, J. (2007) Update on human prion disease. Biochim Biophys Acta. 1772(6): 598 -609 Principles of Molecular Virology © Elsevier, 2011.