Evolution Flashcards
What is the origin of viruses? Name and explain the different theories
- regressive evolution: viruses are derived from intracellular parasites, loss of almost aöö genes not required for basic replication
- cellular origin: viruses are developed from parts of the cell and developed the capacity for autonomous replication
- coevulution with host: viruses developed from self replicating molecules in parallel to the evolution of their hosts
define living organisms. Why are viruses thus not included?
all living organism contain probably 34 ribosomal protein genes which are still shared by archaeal (archis), bacterial and eucaryotic organisms –> viruses do not encode for ribosomal proteins
Are prokaryotic and eukaryotic more infected by RNA or DNA viruses?
prokaryotic: almost exclusively DNA
eukaryotic: more RNA than DNA viruses
Explain the evolution model for euk. RNA viruses?
- commen gene / enzyme for all RNA viruses: RdRp
- +RNA developed fropm cellular RT-coding introns
- dsRNA viruses developed from + RNA viruses
- -RNNA viruses developed from dsRNA viruses
define evolution of viruses
constant change of a virus population under selection pressure
define mutation
inheritable, stable change of the genetic information
name types of mutation
- point mutation
- recombination: deletion, duplication, insertion, reassortment
Name mechanism of virus evolution
- mutation
- recombination
- reassortment
- integration of cellular genes
why are phenotypic mixing and complementation not a mechanism of virus evolution?
they are not a stable change –> no mutation
define homologous recombination
recombination partners show significant sequence homologies
e.g: two poliovirus genomes
define non-homologous recombination
recombination partners show no significant sequence homologies
e.g.: viral genome and cellular mRNA
What role do polymerases play in evolution? Give examples
polymerases have error rates
RNA Polymerases have also no proof reading function
bacterial DNA polymerases: Taq has no proofreading, Pfu has one
what is a quasi species?
RNA viruses as populations of genetic variants
Name selection pressures viruses experience
- environment (virostatika)
- competition pressure
- counteraction of host (immune response)
How do bottle neck experiments work?
- slightly diverse population needed
- very strong selection. e.g. by neutralizing monoclonal antibodies or antivirals in cell culture supernatants
- massive reduction of hgeterogeneity in population
what are the consequences of Evolution of viruses? name viral examples
- change in host range: HIV, Influenza, SARS
- increase/ decrease of virulence: Influenza, Polio
- immune escape: Lentiviruses, HCV, Influenza
Where do HIV-1 and HIV-2 originate from?
HIV-1: chimpanzees
HIV-2: white collared monkey
How many independent transmission of HIV-1 to humans are there?
3
what mediates the change of host range in parvo viruses infecting animals?
mediated by a few amino acid changes in capsid protein
–> Adaption to transferrin receptor of host species
which type of recombination is important for segmented genomes of RNA viruses?
reassortment
How does reassortment work in influenza?
- infection of one cell with two viruses
- genome segments of the two different viruses randomly packed into one new virion
What is the molecular basis of genetic/antigenic drift vs shift? What is the consequence?
drift: point mutations –> slow, minor changes of properties and antigenicity
shift: reassortment –> very rapid, massive change of properties and antigenicity
Can genetic reassortment happen between avian and human influenza A in swine?
yes
characterize avian influenza infection
- highly virulent
- most influenza viruses are not virulant for poultry and replicate only locally in the gut
What can cause massive enhancement of virulence in influenza A? Why?
mutation at HA cleavage site because HA cleavage is a prerequisite for infectivity –> fusion peptide exposed by cleavage–> usually extracellular cleavage (local restriction since protease only occurs locally) but a locally restricted mutation (poly basic cleavage site in HA) can lead to intracellular cleavage by furin and thus systemic spread –> released viruses are infectious without further activation steps
What decides between local or systemic virus spread / low or high virulence in influenza A infection in humans?
HA- cleavage
What was the rabbit pox experiment in australia and why was it not effective? Why were prior lab experiments missleading?
release of myxomatosis virus to control the population of rabbits –> first efficient killing of rabbits but later adaption between host and viurs –> mortality rate much lower
prior experiments misleading because higher survival rate when ambient temperature is higher
How does attenuation of viruses in cell culture work? e.g poliovirus live vaccine strains
- passaging of viruses on cultured cells (especially cells derived from non host species) may lead to attenuated virus variants with decreased virulence
- inefficient replication or receptor binding
What is the problem with live vaccine polio straions? What is the consequence?
reversion of poliovirus 3 to wildtype –> only killed SALK vaccine is used now
What are risk factors for reappearance of polio?
- wt virus in patient samples at research labs
- vaccine production
- chronically infected persons
- live vaccines
Which strategies can be used to prevent reversion to virulence in live attenuated polio vaccine?
- Cre element in 5’ UTR
- stable mutation in stem V
- mutations lowering the error rate for 3Dpol and lowering the propensity for template switching
Which biotypes of BVDV are there?
non cytopathic and cytopathic
explain two different forms of infection in BVDV
- infection of non pregnant animals –> acute, mostly clinically inapparent
- diaplacentar infection:
a. misscariage if infected too early
b. persisten infection if infected in stage of gastation
what is required for replication and packaging of BVDV genome?
NS2-3 cleavage for replication, no cleavage for packaging
What makes BVDV cytopathic?
RNA recombination: cellular insertions in the viral RNA genome:
- ubiquitin
- NEDD8
- GATE-16
–> substrates for cellular proteases –> altered, deregulated cleavage –> upregulation of replication –> cytopathogenicity
name two models of RNA recombination. Which dependent on viral replication?
- template switching of RdRp during viral RNA replication
- breakage (RNase) and ligation (ligase) of viral RNA genome independently from viral replication
What does RNA recombination look like in BVDV?
- insertions
- duplications
- deletions
mostly non homologous
What does RNA recombination look like in feline coronavirus? What is the consequence?
non homologous via deletions –> mutant kills cat, prior infection without massive symptoms
Define immune escape. Which viruses use this strategy?
= escape from the immune response of the host –> Lentiviruses (HIV), HCV
Name mechanisms of virus evolution
- genetic variability: change of virulence, adaptation
- correction of lethal mutations –> genome conservation, repair of viral genomes, genetic stability
- generation of novel viruses
Name examples for generation of novel viruses
- alphaviruses
- dengue virus
What are essential steps in RNA replication for RNA recombination?
- discontinous transcription
- cap snatching
