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VIROLOGY > 4 – Viral Genetics and Evolution > Flashcards

4 – Viral Genetics and Evolution Flashcards

1
Q

Phylogenetic trees

A
  • Longer the horizontal line=more genetic change
  • Vertical distances=no significance
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2
Q

What is a clade?

A
  • Groups of similar viruses based on their genetic sequences
  • Genetically distinct
  • May not be antigenically distinct
  • *how does a particular genotype relate to phenotype
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3
Q

Variant

A
  • Genetically distinct lineage of virus that has one or more mutations
    o Genetic differences do NOT necessarily lead to functional differences
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4
Q

Strain

A
  • Variant that has unique and stable phenotypic characteristics that differ from the original virus
  • Differences in
    o Transmissibility
    o Diseases severity
    o Susceptibility to antiviral treatments
    o Vaccination
    o Immunity
  • *all strains are variants, not all variants are strains
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5
Q

Isolate

A
  • From natural host
  • Can be a population of viruses (quasispecies)
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6
Q

Serogroup

A
  • Group with common antigens
  • Group specific antigens make up internal conserved proteins that define the species of the virus
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7
Q

Serotype

A
  • Type specific antigens make up external variable proteins (ex. glycoproteins) that differentiate between members of that species
  • Defined by basis of neutralizing antibodies
  • *vaccination against one serotype will NOT protect against infection by other serotypes
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8
Q

Neutralizing antibodies define type-specific antigens (serotypes)

A
  • Antibodies that neutralize one serotype will NOT neutralize viruses of a different serotype
  • Ex. FMDV-7 serotypes
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9
Q

Polyclonal antibodies

A
  • Recognize many epitopes on the antigen (ex. a viral glycoprotein)
  • One or more epitopes can change w/o changin the reaction with the typing antiserum
    o Typing antiserum can react with different strains, different strains can have the same serotype
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10
Q

What is diversity generated by?

A
  • Mutation
  • Recombination
  • Reassortment of viral genes
  • *DNA viruses replication with higher fidelity
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11
Q

Replication fidelity (DNA viruses)

A
  • DpDp have proofreading capacity
  • High=based on accurate base pairing during genome replication
    o ESSENTIAL TO MAINTAIN genome integrity
  • Ex. small DNA viral genomes: replication is very accurate
  • Ex. ssDNA viral genomes: higher rates and evolve rapidly
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12
Q

Homologous replication (DNA viruses)

A
  • Exchange of genetic information between any pair of related DNA sequences
  • *all viral DNA genomes under go it
  • *important factor of DNA virus evolution
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13
Q

Site specific recombination (DNA viruses)

A
  • Genetic information exchanges at specific short DNA sequences that are recognized by proteins that catalyze the exchange
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14
Q

What drives the evolution of RNA viruses?

A
  • Lack of replication fidelity
  • Reassortment
  • Recombination
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15
Q

Lack of replication fidelity (RNA viruses)

A
  • RT and most RdRp lack proofreading capacity
    o If base is mistakenly incorporated the error is NOT repaired
  • Many polymerization errors cause lethal changes OR appear in infectious progeny virions
  • Ex. Nidovirales: exception to the rule
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16
Q

Nidovirales (RNA viruses)

A
  • RNA synthesis machinery includes a 3’ – 5’ exonuclease
  • Nuclease inactivation increases mutation rate
17
Q

Base substitutions and frameshifts lead to (RNA viruses)

A
  • Misincorporation
  • Dislocation
18
Q

Reassortment (RNA viruses)

A
  • Exchange of entire RNA molecules between viruses with segmented genomes
    o If co-infected cells: entire genome segments from EITHER parental virus can be assembled into progeny virions
  • Can occur at HIGH frequencies
  • Ex. influenza viruses
19
Q

Antigenic shift

A
  • Genome segment reassortment
  • Lack of pre-existing immunity to novel HA facilitates transmission
  • Can also occur by recombination
20
Q

Antigenic drift

A
  • Small antigenic changes in the HA protein generated by mutation are selected for to EVADE immune responses
21
Q

Recombination (RNA viruses)

A
  • Important source of genetic diversity in DNA viruses
  • RNA viruses: exchange nucleotide sequences between different RNA molecules
    o Important for increasing genetic diversity
    o Can occur with HIGH frequency
22
Q

Homologous recombination (RNA viruses)

A
  • Occurs at same site in both paretnal geomes
  • Recombinant has parental genomic structure
23
Q

Non-homologous recombination (RNA viruses)

A
  • Occurs at different sites in paretnal genome
  • Can result in duplication or deletion
    o Duplication: implications for packaging into icosadhedral capsids
    o Deleted: implications for replication
24
Q

Recombination is common among Enteroviruses (EV) genus (RNA viruses)

A
  • Intertypic recombination implicated in emergence in most pathogenic vaccine-dervied polioviruses
  • Oral polio vaccine composed of live attenuated strains of 3 poliovirus types
25
Q

Recombination: BVDV (RNA viruses)

A
  • *caused pathogenesis
  • Fetal infection (1st trimester) is NOT pathogenic
  • RNA recombination produces a virus that cuases SEVERE GI disease after birth
    o Produces selective advantage b/c pathogenic viruses outgrow non-pathogenic ones
26
Q

Potential mutations

A
  • Silent
  • Non-silent mutation
    o Lethal mutation
    o Viable: indifferent, favourable, detrimental
27
Q

Quasispecies

A
  • Virus populations exist as dynamic distributions of nonidentical related replicons
  • Steady-state equilibrium population comprises multiple particles with genetic DIFFERENCES
  • Selection events (bottlenecks) may confer a replication advantage for particular mutants=found in all progeny genomes
    o Those with lower fitness may sometimes outcompete=quasispeices effect OR survival of the flattest
  • *diversity of population is critical for survival
28
Q

What are 3 constraints to viral evolution?

A
  • Genome
  • Interactions with host-cell proteins
  • pathogenesis
29
Q

Constraints to viral evolution: genome

A
  • Icosahedral capsids have DEFINED CAPACITY, fixes the genome size
  • Functionality of critical viral proteins/ezymes
30
Q

Constraints to viral evolution: interactions with host-cell proteins

A
  • Must be able to interface with host cell for replication
31
Q

Constraints to viral evolution: pathogenesis

A
  • Increases in pathogenesis may KILL host and LIMIT replication/spread

VIROLOGY (12 decks)

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