VIRAL GENETICS

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VIRAL GENETICS

• PATHOGENESIS
• LIFE CYCLES
• VACCINE DEVELOPMENT
• DRUG RESISTANCE

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VIRAL GENETICS
DNA chromosomes of eukaryotic host organisms
generally require geologic time spans to evolve
to the degree that their RNA viruses can achieve
in a single human generation.
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VIRAL GENETICS

• VIRUSES GROW RAPIDLY
• A SINGLE PARTICLE PRODUCES A LOT OF PROGENY
• DNA VIRUSES SEEM TO HAVE ACCESS TO PROOF READING,
  RNA VIRUSES DO NOT SEEM TO

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NATURE OF GENOMES

• RNA or DNA
• SEGMENTED OR NON-SEGMENTED

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GENETIC CHANGE

• MUTATION
• RECOMBINATION

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ORIGIN OF MUTATIONS

• SPONTANEOUS
• tautomeric form of bases
• polymerase errors

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Tautomeric forms of bases
most of time
rarely
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ORIGIN OF MUTATIONS

• SPONTANEOUS
• tautomeric form of bases
• polymerase errors

mutation rates usually higher in RNA viruses
(lack of proof reading)
why do some viruses seem to alter very little,
even though one would expect high mutation rates?
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ORIGIN OF MUTATIONS

• SPONTANEOUS
• PHYSICALLY INDUCED
• UV light , especially problem if no access to
  repair
• X-rays
• CHEMICALLY INDUCED

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TYPES OF MUTATION

• POINT
• INSERTION
• DELETION

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PHENOTYPES

• PHENOTYPE
• the observed properties of an organism

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PHENOTYPIC CHANGES

• CONDITIONAL LETHAL - multiply under some
  conditions but not others - wild-type (wt) grows
  under both sets of conditions
• temperature-sensitive (ts) mutants do not grow at
  higher temperature (altered protein)
• host-range mutants do not grow in all the cell
  types that the wt does

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PHENOTYPIC CHANGES

• PLAQUE SIZE
• may show altered pathogenicity
• DRUG RESISTANCE
• important in the development of antiviral agents
• ENZYME-DEFICIENT MUTANTS
• some genes can be optional in certain
  circumstances

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PHENOTYPIC CHANGES

• HOT MUTANTS
• grow better at elevated temperature than wt
• less susceptible to host fever response
• ATTENUATED MUTANTS
• milder (or no) symptoms
• vaccine development
• pathogenesis

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GENETIC CHANGE

• MUTATION
• RECOMBINATION

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RECOMBINATION

• Exchange of information between two genomes

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RECOMBINATION

• classic recombination

common in DNA viruses
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COPY CHOICE RECOMBINATION

• ve strand 1

• ve strand 2

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COPY CHOICE RECOMBINATION

• ve strand 1

• ve strand 2

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COPY CHOICE RECOMBINATION

• strand

• strand

• - strand

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COPY CHOICE RECOMBINATION

• strand

• strand

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Other methods recombination

• Take advantage quirks in virus replication
• eg. Coronaviruses (include SARS virus)

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RECOMBINATION - SOME USES

• mapping by recombination frequency
• mapping by marker rescue

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RECOMBINATION - SOME USES

marker rescue

• TK - mt

• TK mutant HSV

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RECOMBINATION - SOME USES

• mapping by recombination frequency
• mapping by marker rescue
• development of recombinant viruses for vaccines
  and therapeutic reasons

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RECOMBINATION - SOME USES

• TK

• vaccinia virus

• T

• K

• rabies G

• vaccinia virus for use
• as rabies vaccine

• rabies G

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raccoon eating bait with rabies vaccine in it
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REASSORTMENT
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REASSORTMENT

• form of recombination (non classical)
• very efficient
• segmented viruses only
• used in some new vaccines

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INFLUENZA VIRUS

• cold adapted
• temperature-sensitive
• attenuated
• live vaccine
• intranasal delivery
• approved 2003

adapted fromTreanor JJ Infect. Med. 15714
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NON-SEGMENTED NEGATIVE STRAND RNA VIRUSES

• no classical recombination
• no copy choice
• no reassortment
• least ability to exchange genetic material

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COMPLEMENTATION

• Interaction at the functional level, NOT the
  nucleic acid level

Progeny virus assembled using wt N and wt M
proteins Genomes in progeny are either ts M or ts
N
mutants which can complement are generally in
different genes
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DEFECTIVE VIRUSES

• lack gene(s) necessary for a complete infectious
  cycle
• helper virus provides missing functions

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DEFECTIVE VIRUSES

• some examples of defective viruses
• some retroviruses (use related helper)
• hepatitis delta virus (uses unrelated helper)

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DEFECTIVE INTERFERING (DI) VIRUSES (PARTICLES)

• decrease replication of helper virus
• compete for viral precursors, etc.
• may modulate wt infections
• occur naturally eg. DI measles virus in subacute
  scelerosing panencephalitis - SSPE

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PHENOTYPIC MIXING
no changes in genome possibly altered host
range possibly resistant to antibody
neutralization
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PHENOTYPIC MIXING

• PSEUDOTYPE