2-10 RNA Viruses I

Question 1

What is the general scheme of RNA virus replication?

Answer 1

• RNA is the genetic material AND the template for protein synthesis
• RDRP allows for dual purpose of replication: to copy the genome (replication) and make mRNA (transcription)

Question 2

How can viruses make RNA from RNA?

Answer 2

• RNA-Dependent RNA polymerase (RDRP) is encoded by RNA viruses to copy their RNA genomes and to synthesize mRNA from RNA templates
• (+) strand = sense strand = mRNA
• (-) strand = antisense strand = template for mRNA

Question 3

What are some characteristics of RNA-dependent RNA polymerase (RDRP)?

Answer 3

• RDRP typically acts in the cytoplasm; replication often occurs on cell membranes to concentrate all components and increase efficiency (exception: influenza)
• Fidelity is low: RDRP does not proofread → high error rates
• Rapid evolution by recombination: exchanging large sections → new genomes
• Reassortment of genome segments: segmented RNA viruses can mix segments if the cell is infected with multiple strains
• Large RNA virus genetic diversity: frequent mutations, new diseases, less effective drugs/vaccines; viruses are not pure populations (quasispecies)
• (-) RNA and dsRNA viruses MUST package RDRP in virion; (+) RNA viruses may or may not

Question 4

What are the clinical features of poliovirus?

Answer 4

• Picornaviridae, enterovirus
• (+) ssRNA genome, linear mRNA molecule
• Infects GI epithelial cells, may spread to muscles and neurons
• Vaccination with live or killed virus
• Fecal-oral transmission; persists in water supply; infects only humans
• 95% asymptomatic acute GI infection; 5% mild disseminated disease; 1% paralytic infection of motor neurons
• Can be diagnosed by serology or motor neuron involvement (eyes)
• Support breathing if necessary

Question 5

What is the life cycle of poliovirus?

Answer 5

• Poliovirus binds to receptor
• Capsid proteins become hydrophobic, form transmembrane pore through which RNA genome enters, and are opened by receptor
• Uncoating at the plasma membrane
• Genomic RNA (+) sense → polyprotein
• Polyprotein cleaved into virion proteins (VPs) via VP protease cross-cutting
• Enzymatic VPs convert cell → vesicles
• In vesicles, 3D^pol (RDRP): (+) → (-) → (+)(+)(+)…
• Protein accumulates
• Capsids crystallize around genome
• Egress via lysis