© elsevier, 2011.principles of molecular virology subviral agents satellites and viroids –...
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Principles of Molecular Virology © Elsevier, 2011.
Subviral AgentsSubviral Agents
• Satellites and viroids – parasites of parasites!
• Prions - infectious protein molecules
Principles of Molecular Virology © Elsevier, 2011.
SatellitesSatellites
• 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.
ViroidsViroids
Very small (200- to 400-nt) rod-like RNA molecules
Principles of Molecular Virology © Elsevier, 2011.
Hepatitis delta virus (HDV)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.
PrionsPrions
• 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 © Elsevier, 2011.
Pathology of Prion DiseasesPathology 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 AnimalsTSE in Animals
• Scrapie
• Transmissible Mink Encephalopathy (TME)
• Feline Spongiform Encephalopathy (FSE)
• Chronic Wasting Disease (CWD)
Principles of Molecular Virology © Elsevier, 2011.
Bovine Spongiform Bovine Spongiform Encephalopathy (BSE)Encephalopathy (BSE)
Principles of Molecular Virology © Elsevier, 2011.
Human TSEsHuman TSEs
• Sporadic - Creutzfeldt–Jakob disease (CJD)• Iatrogenic/acquired TSE (neurosurgery, transplantation)• Familial (inherited)• vCJD (from BSE)
Principles of Molecular Virology © Elsevier, 2011.
Molecular Biology of PrionsMolecular 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.
PrPPrP
Principles of Molecular Virology © Elsevier, 2011.
Prion species barrierPrion species barrier
Principles of Molecular Virology © Elsevier, 2011.
PrPC and PrPScPrPC and PrPSc
Principles of Molecular Virology © Elsevier, 2011.
SummarySummary
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 ReadingFurther 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