Virus Evolution

1. Virus Evolution

2. Mechanisms of viral evolution Evolution: the constant change of a viral population in the face of selective pressures. Mutation Recombination Reassortment Selection Positive and negative pressure select for particular preexisting mutants.

3. Basic point: Virus evolution is fast • Fast generation time. • Produce large numbers of progeny. • High rates of mutation.

4. Virus-infected cells produce large numbers of progeny • Infection of a single cell by poliovirus can yield up to 104 viral particles. • In a person, up to 109 – 1011 particles can be produced per day. • Enough to infect every person on the planet.

5. Evolution requires mutation: High mutation rates (genome replication is inaccurate) • Mutations occur when nucleic acids are copied (i.e. genome replication). • Error rate of human DNA polymerase is approximately 10-9 (3 mutations per replication of the human genome). • Error correction machinery lowers this to 10-11 • Virus RNA and DNA polymerases • are much more error prone. • RNA dependent RNA pol: 10-3 – 10-6 • DNA polymerases: 10-6 – 10-7

6. Quasispecies Quasispecies: Virus populations as dynamic distributions of nonidentical but related replicons. • An RNA virus with a genome of 10 kb • RDRP error rate of 10-5 • 1 mutant in 1 position for every 10 virions produced. • If 109 viral particles produced in a person per day, then 108 mutant progeny are being produced in that one individual each day of infection. • Quasispecies- allow viruses with recessive mutations to be maintained (genetic complementation)

7. Error Threshold The error threshold: Error threshold is a mathematical parameter that measures the complexity of the information that must be maintained to ensure survival of the population. • The point at which accumulated mutations reduce fitness • Too much mutation can be lead to loss of vital information • Too little mutation can lead to host defenses overcoming the virus. Fitness: the replicative adaptability of an organism to its environment. The greatest fitness is when mutation rates approach the error threshold.

8. Error Threshold • Factors limiting mutations/evolution • mutations in cis acting factor required for replication, mRNA synthesis, packaging of genomes will decrease fitness. • Constrained by interactions with the host. • Genome size. • Antimutators: mutations in polymerase that reduce frequency of incorporation errors. • Increased fidelity is not advantageous in nature and not selected. • Error Catastrophe: extinction of an virus as the result of excessive RNA mutations. • example: the antiviral drug ribavirin

9. Genetic bottleneck Extreme selective pressure on a small population. Results in loss of diversity and accumulation of non-selected mutations.

10. Genetic information exchange Genetic information is exchanged by recombination of genome segments. Infection of a cell by two different viruses can result in exchange of genetic information, resulting in production of mixed progeny. Recombination of genome segments. Reassortment. Acquisition of cellular genes

11. Template switching: polio virus • HIV 2 mechanisms: • Copy choice: during (-) strand synthesis • Strand assimilation: during (+) strand synthesis Recombination

12. Reassortment

13. Shift vs Drift • Genetic drift: slow accumulation of mutations in a population. Due to copying errors and immune selection. • Genetic shift: a major genetic change caused by recombination or reassortment of genomes. Drift Shift

14. Evolution is both driven and constrained by the fundamental properties of viruses • Despite lots of sequence diversity, viral populations maintain stable master or consensus sequences. • The sequence that reflects the most common choice of nucleotide or amino acid at each position. • Diversity limited be the to ability to function within certain constraints. These include: • Particle geometry: eg. Icosahedral capsids limit genome size by limiting volume. • All genomes are composed of nucleic acids: limits solutions to replication or decoding of viral information. • Requirement for interactions with host cell machinery. • Requirements for interactions within the host.

15. Two general pathways for virus evolution virus evolution is inescapable • Co-evolution with host • Advantage: prosperous host = prosperous virus • Disadvantage: virus shares same fate as host. • Typically used by DNA viruses. • Infection of multiple host species. • Advantage: if one host species is compromised the virus • can replicate in another • Disadvantage: cannot optimize for any one situation. • ( a mutation that enhances replication in one host may decrease replication in another) • Typically used by RNA viruses

16. Co-evolution • Viruses and hosts tend to co-evolve toward symbiotic or at least mutualistic relationships. • Highly virulent virus will kill the host too soon • Too exposed and the host will kill it. Host-virus interactions

17. L-A M1 Dead Cell Toxin Co-evolution and fitness • Example: the yeast killer virus. • L-A is a metabolic parasite of the host • M is a parasite of L-A • However, M confers a selective advantage on host. • Host tolerates L-A to maintain M. • L-A tolerates M to stay in good graces with host.

18. Problem: no fossil record. • Solution: Genomes as the fossil record. • Relationships among different viral genomes provide insight into virus origins. This is the basis of molecular taxonomy. Fig. 20.2

19. Co-evolution with host populations. • Association of a given viral genome sequence with a particular host group. • e.g. different papillomaviruses subtypes are more prevalent in different human populations. • Can use viruses to trace human origins

20. The origin of viruses (Table 20.3). 1. Regressive evolution (parasitism) • Viruses degenerated from previously independent life forms • Lost many functions • Retain only what they needed for parasitic lifestyle 2. Cellular origins • Viruses derived from subcellular functional assemblies of macromolecules that gained the capacity to move from cell to cell. 3. Independent entities • Evolution on course parallel to that of cellular organisms. • Evolved from primitive, pre-biotic self-replicating molecules.