Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
How did viruses originate? “Viral Mutation Evolved” Media: Pastel on paper WALTER DUPRIEST acanthusarts.org 1 • Virus first hypothesis – Originated before cells • Viruses from all three domains have similar characteristics • Predate LUCA LUCA Original virus prebiotic RNA molecule 2 • 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 3 Original RNA organism DNA is more stable Less prone to mutations Larger more complex proteins Protection against enzymes that degrade RNA DNA viruses RNA viruses Did DNA organisms evolve 3 separate times or just once? Viral DNA become incorporated into cells DNA genes had a selective advantage 4 • 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 (2nd ed.) by Voyles. McGraw-Hill Co., Inc. 5 Rickettsia Chlamydia Pox virus ds DNA 100 genes No cell wall 0.3 and 1.0 mm in diameter 6 Mimivirus A unique virus 7 Mimivirus Mimicking microbe • 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 8 ASM News 71(6):278-284 Gram stain TEM images Electron micrograph 9 Mimivirus 400 nm = 0.4 mm 10 11 • 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 12 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 13 Mimivirus is hypothesized to be the ancestor of a virus which contained more eukaryotic genes 14 Mimiviruses are an exception that provide evolutionary clues to the origin of life Raoult 2005 ASM News 71(6):278-284 15 Proteinaceous Infectious Agents Transmissible Spongiform Encephalopathies • Prions • • • • Normal proteins that become misfolded in the mammalian brain • PrP • Holes in the brain • • • • • Creutzfeldt-Jakob Disease New variant CJD Kuru Gerstmann-Straussler-Scheinker Syndrome Fatal Familial Insomnia • • • • Scrapie in sheep & goats Bovine spongiform encephalopathies (BSE) Chronic wasting in elk and mule deer Similar diseases in cat & mink Spongiform encephalopathies Human diseases Dementia; early neurologic signs Several animal diseases 16 17 • 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 18 19 • Amino acid sequence can fold into two different structures Stanley B. Prusiner – Cellular PrP – Prion PrP PrPc PrPsc The Nobel Prize in Physiology or Medicine 1997 • 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 20 Cellular PrP PrPc a helices Prion PrP PrPsc Pleated sheets 21 the PrPsc accumulates primarily in the cerebral cortex 22 nobelprize.org How does PrPsc 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 23 • 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 24 • 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 PrPsc 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 25 26 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 27 www.cdc.gov 28 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) 29 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 30