Micro-L9-Viral Evolution

why does “the virus: not describe what exists in a host?

• virus particles in a host are NOT identical

• sequencing samples gives a consensus sequence- represents the population, not each individual particle

• viral populations have genetic variation- constantly adapting within the host

how does genetic variability arise in viruses?

1. polymerase errors- point mutation

2. genetic recombination- exchange of genetic material between viruses. site specific or homologous genome

3. reassortment- in viruses with segmented genomes such as infleunza- segments can swap during co-infection.

4. horizontal gene transfer- viruses steal genes from host or give genes to host

5. gene duplication- more copies, more mutations.

what are the main drivers of viral evolution?

1. high progeny numbers such as HIV- millions of virions means more chances for mutations

2. transmission- successful spread allows genetic changes to persist

3. high mutations rates- viral polymerase lack proofreading compared to host polymerases

4. selection pressures- immune system, drugs and host environment

5. quasi species effect- diverse populations allow for rapid adaptation

what is the monkey theorem?

• large numbers of virus particles means a higher probability of mutations that improve virulence or host adaptation

• sheer number of virions drive the likelihood of adaptive mutations. large number of virus particles are produced in a short amount of infection in acute

how does viral genome type influence mutation rates?

• RNA viruses: higher mutation rates than dsDNA

• retroviruses- fast mutation due to reverse transcriptase errors

• DNA viruses- slower mutations as DNA polymerase has proofreading

• mutation rates correspond to viral polymerasefidelity/accuracy

why do RNA viruses mutate faster than DNA viruses? what is an exception?

• RNA polymerase lacks efficient proofreading mechanisms and errors accumulate

• DNA polymerases typically correct mistakes and reducing mutations

• high mutation rates enable rapid adaptation to host immune response, drugs, environment changes

• COVID has a more complex RNA genome and polymerase can correct mistakes

what factors influence mutation rates in viruses?

1. polymerase fidelity- accuracy means fewer muations

2. genomic architecture- dsDNA is more stable. also IRES in polio- needed for replication so mutations are rarer here

3. error threshold- maximum mutations tolerated before replication fails

4. replication speed- faster means more mutations

5. length of infection- chronic infection allow more mutations that acute infections

6. NS- favours advantageous

what is the quasi species effect in viruses?

• virus populations are not all identical

• high mutations means individuals virions differ from each other genetically from parental virus

• some mutations are advantageous and some are disadvantegous

• consensus genome sequences: only approximate populations

how does the quasi species effect develop?

• infection starts with a small population

• when replication occurs- mutations do too and selective pressure in the host favour survival of fitter variants

• these survivors form a genetically diverse population which is then transmitted

• leads to rapid adaptation and makes vaccine development more difficult. for HIV, highly diverse and virus variants can escape recognition if a vaccine were to be made

what is the viral error threshold? how can this be used in therapeutics?

• maximum number of mutations a virus can tolerate while remaining viable

• too many mutations and proteins lose function and cannot replicate and be viable

• too few mutations and viruses cannot adapt to selective pressures

• a balance is needed for survival and evolution

• moolnupiravir in COVID- targets RNA dependent RNA polymerase and adds mismatched nucleotides and increases mutations until it becomes non function

what are genetic bottlenecks in viral populations? what happens? and when do they occur in infections?

• occur when viral population diversity shrinks too much

• reduced diversity means less ability to adapt to selective pressures and become less fit

• a small dose infection in a person- they cannot initiate replicative infection which leads to a dead end infection as it doesn’t have diversity needed to establish an infection

how do virus populations avoid bottlenecks?

• recombination or reassortment

• large number of particles means a particle with a negative mutation can be compensated by a virion that doesn’t have it

• even if recombination is rare- it may have a powerful advantage as it can be passed on

explain examples of virus evolution

• host restriction drives point mutation: influenza in aquatic birds replicates in gastrointestinal tract 39 degrees in humans in respiratory tract 32 degrees.

• viral enzymes polymerase are temperature sensitive. this is a SELECTION PRESURE! avian influenza has a E627K in PB2 polymerase protein and allows it to interact with importin in humans- transport to nucleus

• myxomatosis poxvirus: European rabbits in Australia with no predators. myxomatosis virus released to control rabbit populations. 99.8% mortality in year 1 and 25% mortality in year 2. rabbits developed resistance- rabbits who survived were likely to pass resistance genes