Viral Genetics

1. 1
VIRAL GENETICS
•PATHOGENESIS
•LIFE CYCLES
•VACCINE DEVELOPMENT
•DRUG RESISTANCE
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2. 2
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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3. 3
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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4. 4
NATURE OF GENOMES
•RNA or DNA
•SEGMENTED OR NON-SEGMENTED
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5. 5
GENETIC CHANGE
•MUTATION
•RECOMBINATION
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6. 6
ORIGIN OF MUTATIONS
•SPONTANEOUS
–tautomeric form of bases
–polymerase errors

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7. 7
Tautomeric forms of bases
most of time rarely
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8. 8
ORIGIN OF MUTATIONS
•SPONTANEOUS
–tautomeric form of bases
–polymerase errors

why do some viruses seem to alter very little, even though
one would expect high mutation rates?
mutation rates usually higher in RNA viruses (lack of proof
reading)
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10. 10
ORIGIN OF MUTATIONS
•SPONTANEOUS
•PHYSICALLY INDUCED
–UV light , especially problem if no
access to repair
–X-rays
•CHEMICALLY INDUCED
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11. 11
TYPES OF MUTATION
• POINT
•INSERTION
•DELETION
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PHENOTYPES
PHENOTYPE

–the observed properties of an organism
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13. 13
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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14. 14
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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15. 15
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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16. 16
GENETIC CHANGE
•MUTATION
•RECOMBINATION
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17. 17
RECOMBINATION

Exchange of information between two
genomes
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RECOMBINATION
‘classic’ recombinationcommon in DNA viruses
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19. 19
COPY CHOICE
RECOMBINATION
template switch
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20. 20
COPY CHOICE
RECOMBINATION
continues copying
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21. 21
COPY CHOICE
RECOMBINATION
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22. 22
COPY CHOICE
RECOMBINATION
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23. 23
Other methods recombination
•Take advantage quirks in virus replication
–eg. Coronaviruses (include SARS virus)
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24. 24
RECOMBINATION - SOME USES

•mapping by recombination frequency
• mapping by marker rescue
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25. 25
RECOMBINATION - SOME USES
marker rescue
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26. 26
RECOMBINATION - SOME USES

•mapping by recombination frequency
•mapping by marker rescue
•development of recombinant viruses for
vaccines and therapeutic reasons
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27. 27
RECOMBINATION - SOME USES
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28. 28
raccoon eating bait with rabies vaccine in it
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29. 29
REASSORTMENT
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30. 30
REASSORTMENT
• form of recombination (non classical)
• very efficient
• segmented viruses only
–can occur naturally
• used in some new vaccines
–eg for influenza and rotaviruses
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31. 31
adapted fromTreanor JJ Infect. Med. 15:714
•cold adapted
•temperature-sensitive
•attenuated
•live vaccine
•intranasal delivery
•approved 2003
INFLUENZA VIRUS
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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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other aspects of viral genetics
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34. 34
COMPLEMENTATION
Interaction at the functional level, NOT the nucleic
acid level
mutants which can complement are generally in different genes
Progeny virus assembled using wt N and wt M proteins
Genomes in progeny are either ts M or ts N
ts mutant 1 ts mutant 2
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35. 35
DEFECTIVE VIRUSES
•lack gene(s) necessary for a complete
infectious cycle
•‘helper’ virus provides missing functions
package me!copy me!
package me! copy me!
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36. 36
DEFECTIVE VIRUSES
•some examples of defective viruses
–some retroviruses (use related helper)
–hepatitis delta virus (uses unrelated helper)
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37. 37
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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38. 38
PHENOTYPIC MIXING
no changes in genome
possibly altered host range
possibly resistant to antibody neutralization
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39. 39
PHENOTYPIC MIXING
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