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Flashcards in RNA Viruses I Deck (17)

Relevance of RNA viruses

-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


Common features of RNA viruses

-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


How to make RNA from RNA

-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


RNA-dependent RNA polymerase

-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


Where does RDRP do its job

-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


Fidelity of RDRP

-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


Rapid Evolution by Recombination

-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


Reassortment of Genome Segments

-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


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


Polio Virus

-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


Polio Disease

-transmission: fecal-oral
-persists in water supply

-95% asymptomatic acute GI infection
-5% mild disseminated disease
-1% paralytic infection of motor neurons


Poliovirus entry

-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


Poliovirus Genome Replication

- (+) strand genome RNA (mRNA)
- (-) strand full-length complement
- (+) strand genome RNA (mRNA)

-the same enzymes (RDRP) copies (+) and (-) strands


Switch from mRNA to genome RNA synthesis

-when capsid proteins accumulate, new mRNA is packaged instead of translated


Issue with (+) RNA

-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


Association of RDRP with virions

-All RNA viruses encode RDRP (retroviruses encode reverse transcriptase)
- (-) RNA and dsRNA viruses must package RDRP in the virion
- (+) viruses may or may not package RDRP in the virion
-if RDRP is not present in the virion, then protein synthesis is necessary to make RDRP before replication can begin


Poliovirus Clinical Features

-motor neuron involvement
-serology and culture

-control symptoms, if any
-breathing support if needed