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
• 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 Virology
© Elsevier, 2011.
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 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 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 (FSE)
• Chronic Wasting Disease (CWD)
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 (inherited)
vCJD (from BSE)
Principles of Molecular Virology
© Elsevier, 2011.
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.
PrP
Principles of Molecular Virology
© Elsevier, 2011.
Prion species barrier
Principles of Molecular Virology
© Elsevier, 2011.
PrPC and PrPSc
Principles of Molecular Virology
© Elsevier, 2011.
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 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
© Elsevier, 2011.