1. 1 How did viruses originate? “Viral Mutation Evolved” Media: Pastel on paper WALTER DUPRIEST acanthusarts.org

2. 2 Virus first hypothesis –Originated before cells Viruses from all three domains have similar characteristics Predate LUCA LUCA Original virus prebiotic RNA molecule

3. 3 Escape hypothesis –Fragments of escaped genome Bacteriophages originated in the prokaryotic genome –Derived from an autonomously replicated plasmid Eukaryotic viruses originated from the eukaryotic genome Archaean viruses originated from the Archaean genome –DNA developed from RNA viruses

4. 4 Original RNA organism RNA viruses DNA viruses DNA is more stable Less prone to mutations Larger more complex proteins Protection against enzymes that degrade RNA Viral DNA become incorporated into cells DNA genes had a selective advantage Did DNA organisms evolve 3 separate times or just once?

5. 5 Regressive hypothesis –Reduction of a parasite Facultative parasite become dependent upon the host Evolved towards an obligate parasite / host relationship Similar to the reduction of endosymbiont to the mitochondria and photosynthesis Parasite looses genes and become more dependent upon the host –Rickettsia like organism  Chlamydia like organisms  Pox like virus Prangishvili et al. Viruses of the Archaea: a unifying view. Nature Reviews Microbiology 4:837-848. The Biology of Viruses (2 nd ed.) by Voyles. McGraw-Hill Co., Inc.

6. 6 Rickettsia Pox virus ds DNA 100 genes Chlamydia No cell wall 0.3 and 1.0  m in diameter

7. 7 Mimivirus A unique virus

8. 8 Pathogen of amoebae –Acanthamoeba polyphaga –Microbiologists observed a Gram + coccus within the amoeba Large virus –Diameter of capsid is 400 nm –80 nm fibrils Nucleocytoplasmic Large DNA virus –NCLDV Mimivirus Mimicking microbe

9. 9 Gram stain Electron micrograph ASM News 71(6):278-284 TEM images

10. 10 Mimivirus 400 nm = 0.4  m

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12. 12 Linear ds DNA Approx 1.2 million bp –Largest viral genome –Larger genome than 20 prokaryotic organisms 1262 open reading frames – Putative genes Contains 21 genes that are found in all NCLDV Contains metabolic genes not found in any other virus –Contains genes for nucleotide synthesis, protein synthesis, DNA repair, polysaccharide synthesis genes

13. 13 There are 7 minivirus genes that are present in Eukaraya, Bacteria, and Archaea. A DNA sequence analysis places mimivirus closest to the Eukaraya in the 3 domain system

14. 14 Mimivirus is hypothesized to be the ancestor of a virus which contained more eukaryotic genes

15. 15 Raoult 2005 ASM News 71(6):278-284 Mimiviruses are an exception that provide evolutionary clues to the origin of life

16. 16 Proteinaceous Infectious Agents Transmissible Spongiform Encephalopathies Prions Normal proteins that become misfolded in the mammalian brain PrP Spongiform encephalopathies Holes in the brain Human diseases Creutzfeldt-Jakob Disease New variant CJD Kuru Gerstmann-Straussler-Scheinker Syndrome Fatal Familial Insomnia Several animal diseases Scrapie in sheep & goats Bovine spongiform encephalopathies (BSE) Chronic wasting in elk and mule deer Similar diseases in cat & mink Dementia; early neurologic signs

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18. 18 Originally thought to be a viral disease No RNA or DNA has been isolated Treatment with UV did not reduce virulence Prions have been produced in yeast cells Useful experimental model

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20. 20 Amino acid sequence can fold into two different structures –Cellular PrPPrP c –Prion PrPPrP sc Prion Prp can cause a conformational change in the shape of the cellular PrP Ingesting the prion PrP can cause cellular PrP to convert to disease causing form Prion PrP are not denatured by… –Cooking –UV irradiation –Degradative enzymes Stanley B. Prusiner The Nobel Prize in Physiology or Medicine 1997

21. 21 Cellular PrP PrP c Prion PrP PrP sc  helices Pleated sheets

22. 22 nobelprize.org the PrP sc accumulates primarily in the cerebral cortex

23. 23 How does PrP sc arise? Horizontal transmission from consuming contaminated food or animal feed –Sheep to a cow Veritcal transmission –Mutations in the wildtype prion gene are transmitted from parent to child Spontaneously –Approximately 1 in a million humans develop CJD disease

24. 24 Creutzfeldt-Jakob disease (CJD) –1920’s –1 in a million individuals Mutations in the human PrP gene produced the first prion PrP CJD is inherited –Families of Ashkenazi Jews –Median age of onset is 68 years –Median length of disease 5 months Kuru –Papua New Guinea –Cannibalism nobelprize.org

25. 25 European BSE –Meat and bone meal from sheep were commonly added to animal feed as a protein supplement Scrapie-infected 1980’s –Healthy cattle consumed the PrP sc protein –Developed BSE 1990’s –Approximately 100 individuals in the U.K. and France contracted the new variant CJD Median age of onset is 28 Median length of disease is 14 months Prominent psychiatric/behavioral symptoms; painful dyesthesiasis; delayed neurologic signs –Unpleasant sensations that are produced in response to normal stimuli –Painful tingling, burning and numbness

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27. 27 BSE in the USA December 2003 –An adult Holstein cow from Washington State –The BSE infected cow was imported from Canada in August 2001 2004 –A single BSE American cow March 2006 –A single BSE American cow

28. 28 www.cdc.gov

29. 29 Viroids Smallest known pathogens Naked ss RNA molecules with no protein ~ 246-399 nucleotides No protein encoding genes! Only known to infect plants (e.g., potato spindle tuber viroid, citrus exocortis viroid)

30. 30 Viroids (Continued) Infection can be symptomless or severe in symptoms, even lethal Severe syptoms tend to be growth related suggesting that viroid is a form of “regulatory RNA” that “rebelled” None known in animals or prokaryotes as yet Single-stranded but may appear to be ds based on secondary structure