RNA Viruses I Flashcards
1
Q
Relevance of RNA viruses
A
-huge medical burden- flu, colds, diarrhea, hepatitis C, AIDS
-high mutation rates:
resistance to antivirals, barriers to vaccines, reassortment of genome segments, pandemics
-the next big disease will probably be RNA virus
2
Q
Common features of RNA viruses
A
- RNA is the genetic material AND the template from protein synthesis
- the dual purpose of replication is to copy the genome and make mRNA
- diverse strategies have evolved to accomplish these dual goals
transcription= mRNA synthesis replication= RNA genome synthesis
3
Q
How to make RNA from RNA
A
- viruses use a special enzyme: RNA-dependent RNA polymerase
- RDRP allows RNA viruses to copy their RNA genomes and to synthesize mRNA from RNA templates
- (+) strand = sense strand = mRNA
- (-) strand = antisense strand = template for mRNA
4
Q
RNA-dependent RNA polymerase
A
- cells do not have the enzymes to transcribe RNA from RNA
- therefore all RNA viruses encode an RNA polymerase to copy their RNA genome and make mRNA
- RDRP is highly efficient; poliovirus makes 50K copies in 8 hours
5
Q
Where does RDRP do its job
A
- cytoplasm
- RNA, RDRP, nucleoproteins, and accessory proteins are not floating free in the cytoplasm
- replication often occurs on cell membranes (endosomes, lysosomes, ER vesicles)
- this concentrates all the components and increases efficiency
6
Q
Fidelity of RDRP
A
- fidelity is low
- 4 molecules of poliovirus RDRP bind to the template
- complex dimerize into octomers
- RDRP does not proofread
- Error rates= 1 in 10^3-10^4 nucleotides
- All RNA virus stocks are mixtures of wild type and mutant forms
7
Q
Rapid Evolution by Recombination
A
- exchanging large sections produces new genomes
- hybrid viruses may have new features (antigens, virulence)
- high frequency event: up to 20% of Poliovirus genomes are recombinant after 1 growth cycle
8
Q
Reassortment of Genome Segments
A
- segmented RNA viruses: Reo, Retro, Bunya, Arena, and Orthomyxo, etc (Influenza virus)
- segments can mix if the cell is infected with multiple strains
- new variants may be highly virulent
9
Q
Consequences of RNA Virus Genetic Diversity
A
- mutants arise frequently
- new variants may cause new diseases
- drugs and vaccines lose effectiveness
- viruses are not pure populations
- quasispecies
10
Q
Polio Virus
A
- Picornaviridae, enterovirus
- (+) ssRNA genome, 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
11
Q
Polio Disease
A
- transmission: fecal-oral
- persists in water supply
- infects
pathogenesis:
- 95% asymptomatic acute GI infection
- 5% mild disseminated disease
- 1% paralytic infection of motor neurons
12
Q
Poliovirus entry
A
- poliovirus changes shape after binding to receptor, capsid proteins become hydrophobic
- capsid proteins form pore through membrane
- RNA genome enters cell at plasma or endosome membrane
13
Q
Poliovirus Genome Replication
A
- (+) strand genome RNA (mRNA)
- (-) strand full-length complement
- (+) strand genome RNA (mRNA)
-the same enzymes (RDRP) copies (+) and (-) strands
14
Q
Switch from mRNA to genome RNA synthesis
A
-when capsid proteins accumulate, new mRNA is packaged instead of translated
15
Q
Issue with (+) RNA
A
- collisions occur between RDRP and ribosomes, but they are not a big problem
- translation happens first when RDRP is scarce
- (-) RNA synthesis occurs later when RDRP is abundant
