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 generatio
Trang 2VIRAL 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.”
Trang 3VIRAL 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
Trang 4NATURE OF GENOMES
* RNA or DNA
¢ SEGMENTED OR NON-SEGMENTED
Trang 5GENETIC CHANGE
* RECOMBINATION
Trang 6ORIGIN OF MUTATIONS
* SPONTANEOUS
— tautomeric form of bases
— polymerase errors
Trang 7Tautomeric forms of bases
Trang 12PHENOTYPES
PHENOTYPE
— the observed properties of an organism
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Trang 13PHENOTYPIC 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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Trang 15PHENOTYPIC CHANGES
© “HOT MUTANTS”
— grow better at elevated temperature than wt
— less susceptible to host fever response
Trang 16GENETIC CHANGE
¢ MUTATION
* RECOMBINATION ®&mi
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Trang 17RECOMBINATION
Exchange of information between two
genomes
L7
Trang 18RECOMBINATION
‘classic’ recombination common in DNA viruses
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Trang 19COPY CHOICE RECOMBINATION
Trang 20COPY CHOICE RECOMBINATION
Trang 21COPY CHOICE RECOMBINATION
VD DDD DDD DPD DD DD DPDDPDDDDLPPP DD DPD DPD LP JP DD DPD DDD DDDDDDDLDLKLIY
(VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV
Trang 22COPY CHOICE RECOMBINATION
(VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV VV
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Trang 23Other methods recombination
¢ Take advantage quirks in virus replication
— eg Coronaviruses (include SARS virus)
23
Trang 24RECOMBINATION - SOME USES
* mapping by recombination frequency
* mapping by marker rescue
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Trang 25RECOMBINATION - SOME USES
marker rescue
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Trang 26RECOMBINATION - SOME USES
¢ development of recombinant viruses for
vaccines and therapeutic reasons
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Trang 27RECOMBINATION - SOME USES
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4 rables G
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Trang 28
raccoon eating bait with rabies vaccine in it
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Trang 29REASSORTMENT
Trang 30REASSORTMENT
form of recombination (non classical) very efficient
segmented viruses only
— can occur naturally
used in some new vaccines
— eg for influenza and rotaviruses
30
Trang 31¢ approved 2003 Attenuated Vaccine Virus
liẳdscape ® h†ttp:iwwwwmmedscape com
adapted fromTreanor JJ Infect Med 15:714
Trang 33other aspects of viral genetics
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Trang 34Progeny virus assembled using wt N and wi i proteins
Genomes in progeny are either ts M or ts N
mutants which can complement are generally in different genes
34
Trang 35package me! copy me!
35
Trang 36DEFECTIVE VIRUSES
* some examples of defective viruses
— some retroviruses (use related helper)
— hepatitis delta virus (uses unrelated helper)
36
Trang 37DEFECTIVE 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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Trang 38PHENOTYPIC MIXING
| 7 no changes in genome
possibly altered host range possibly resistant tg antibody neutralization
Trang 39PHENOTYPIC MIXING
`
CP aN PSEUDOTYPE