RNA Virus 1 Flashcards
Picorna
-colds and polio
flavi
hep C and dengue
retro
HIV
corona
MERS-middle east resp syndrome
filo
ebola
rhabdo
rabies
orthomyxo
flu
paramyxo
croup
measles
relevance of RNA viruses
-huge medical problem-flu, colds, diarrhea, hep C, AIDS
-high mutation rates:
-resistance to antivirals
-barriers to vaccines
-reassortment of genome segments
-pandemics
“scariest new bugs”-Quammen
common features of RNA viruses
- RNA is genetic material and template for protein synthesis
- the dual purpose of replication is to copy the genome and make mRNA
- diverse strategies have evolved to accomplish these dual goals
double stranded RNA
-uses RDRP to make + sense mRNA for proteins
ss RNA +
- can be used for protein synthesis
- must use RDRP to make - strand to make copies for more protein synthesis, and RDRP changes - back to + before reading it
ssRNA -
-can be replicated or transcribed to + by RDRP
+strand
-sense strand, coding= mRNA
- strand
- antisense strand
- template for mRNA
how to make RNA from RNA?
- RDRP
- allows viruses to cope their RNA genomes and to synthesize mRNA from RNA templates
RDRP
- cells do not have the enzymes to transcribe RNA from RNA
- therefore all rNA viruses encode and RNA pol to copy their RNA genome and make mRNA
- RDRP is highly efficient-poliovirus makes 50K copies in 8 hours!
where does RDRP do its job?
- cytoplasm-except flu- anchored to something
- RNA, RDRP, nucleoproteins, and accessory proteins don’t float freely in cytoplasm
- replication often occurs on cell membranes (endo, lyso, ER vesicles)
- this concentrates all the components and increases efficiency
fidelity of RDRP is low
- doesn’t proofread, works as an octomer
- error rates of 1 in 10^3-4
- all RNA virus stocks are mixtures of wild type and mutant forms
rapid evolution by recombination
- exchanging larger sections produces new genomes
- hybrid viruses may have new features (antigens, virulence)
- high freq event-up to 20% of poliovirus genomes are recombinant after 1 growth cycle
reassortment of genome segments
- segmented RNA viruses-Reo, Retro, Bunya, Arena, Orthomyxo
- segments can mix if cell is infected with multiple strains
- new variant can be highly virulent-fluuuuu
consequences of RNA virus genetic diversity
- mutants arise frequently
- new variants may cause new diseases
- drugs and vaccines lose effectiveness
- viruses are not pure populations-quasispecies
polio!
- +ssRNA linear mRNA molecule
- infects GI epithelial cells, may spread to muscles and neurons
- vaccination with live or killed virus induces protective antibodies
- WHO Global eradication program underway
- annual cases-296 as of oct 2, 2013
polio disease
- fecal oral
- persists in water
- humans only host
- 95% asymptomatic acute GI infection
- 5% mile disseminated disease
- 1% paralytic infection of motor neurons
polio cycle
- enters cell via endocytosis or just docks- CD155
- ejects genome because capsid is pulled open by interaction with receptors (become hydrophobic)
- mRNA immediately translated to protein-then cleaved by self proteases
- RDRP replicates genome into - strand and copies it many times
- RDRP also transcribes - strand back to + strand so it can be translated
- when there is enough mRNA, RDRP just makes RNA genome to be packaged-when there are enough capsids around
issues with + RNA
- collisions occur b/n RDRP and ribosomes, not big problem
- translation first when RDRP is scarce
- RNA synthesis occurs later when RDRP is abundant-then must be changed back into plus to be packaged
association of RDRP with virions
- all RNA viruses encode RDRP (retro-RT)
- dsRNA and - RNA must package RDRP into virion- can’t be translated first
- +RNA may or may not package
- if RDRP not present, must translate first
polio clinical features
- motor neuron involvement
- serology and culture
- control symptoms, breathing support
- vaccine, sanitation, peace
