© Elsevier, 2011.Principles of Molecular Virology Subviral Agents Satellites and viroids –...

Principles of Molecular Virology © Elsevier, 2011.

Subviral AgentsSubviral Agents

• Satellites and viroids – parasites of parasites!

• Prions - infectious protein molecules


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


ViroidsViroids

Very small (200- to 400-nt) rod-like RNA molecules


Hepatitis delta virus (HDV)Hepatitis delta virus (HDV)

Chimeric molecule with some of the properties of a satellite virus and some of a viroid


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)


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


TSE in AnimalsTSE in Animals

• Scrapie

• Transmissible Mink Encephalopathy (TME)

• Feline Spongiform Encephalopathy (FSE)

• Chronic Wasting Disease (CWD)


Bovine Spongiform Bovine Spongiform Encephalopathy (BSE)Encephalopathy (BSE)


Human TSEsHuman TSEs

• Sporadic - Creutzfeldt–Jakob disease (CJD)• Iatrogenic/acquired TSE (neurosurgery, transplantation)• Familial (inherited)• vCJD (from BSE)


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


PrPPrP


Prion species barrierPrion species barrier


PrPC and PrPScPrPC and PrPSc


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


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

© Elsevier, 2011.Principles of Molecular Virology Subviral Agents Satellites and viroids –...

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