VIRAL GENETICS

• PATHOGENESIS
• LIFE CYCLES
• EMERGING VIRUSES
• 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

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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

• 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 fever
• 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

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 COPY CHOICE
RECOMBINATION

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 COPY CHOICE
RECOMBINATION

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 COPY CHOICE
RECOMBINATION

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RECOMBINATION - SOME USES

• mapping by recombination frequency

• mapping by marker rescue

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RECOMBINATION - SOME USES
marker rescue

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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

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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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adapted from
Treanor JJ Infect. Med. 15:714
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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

package me! copy me!

package me! copy me!

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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

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