Transcript Mimivirus is hypothesized to be the ancestor of a virus which

How did viruses originate?
“Viral Mutation Evolved”
Media: Pastel on paper
WALTER DUPRIEST
acanthusarts.org
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• Virus first hypothesis
– Originated before cells
• Viruses from all three domains have similar
characteristics
• Predate LUCA
LUCA
Original virus
prebiotic RNA molecule
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• 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
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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
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• 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.
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Rickettsia
Chlamydia
Pox virus
ds DNA
100 genes
No cell wall
0.3 and 1.0 mm
in diameter
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Mimivirus
A unique virus
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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
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ASM News 71(6):278-284
Gram stain
TEM images
Electron micrograph
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Mimivirus
400 nm = 0.4 mm
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• 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
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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
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Mimivirus is
hypothesized to be
the ancestor of a
virus which
contained more
eukaryotic genes
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Mimiviruses are an exception that provide evolutionary clues to the origin of life
Raoult 2005 ASM News 71(6):278-284
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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
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•
•
•
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
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• 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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• 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
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Cellular PrP PrPc
a helices
Prion PrP PrPsc
Pleated sheets
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the PrPsc accumulates
primarily in the cerebral
cortex
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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
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• 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
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• 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
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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
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www.cdc.gov
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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)
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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
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