Di truyen hoc virus

VIRAL GENETICS
PATHOGENESIS
LIFE CYCLES
VACCINE DEVELOPMENT
DRUG RESISTANCE
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.”
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
NATURE OF GENOMES
RNA or DNA
SEGMENTED OR NON-SEGMENTED
GENETIC CHANGE
MUTATION
RECOMBINATION
ORIGIN OF MUTATIONS
SPONTANEOUS
tautomeric form of bases
polymerase errors

Tautomeric forms of bases
most of time
rarely
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)
ORIGIN OF MUTATIONS
SPONTANEOUS
PHYSICALLY INDUCED
UV light , especially problem if no access to repair
X-rays
CHEMICALLY INDUCED
TYPES OF MUTATION
POINT
INSERTION
DELETION
PHENOTYPES
PHENOTYPE

the observed properties of an organism
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
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
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
GENETIC CHANGE
MUTATION
RECOMBINATION
RECOMBINATION



Exchange of information between two genomes

RECOMBINATION
‘classic’ recombination
common in DNA viruses
COPY CHOICE RECOMBINATION
COPY CHOICE RECOMBINATION
COPY CHOICE RECOMBINATION
COPY CHOICE RECOMBINATION
Other methods recombination

Take advantage quirks in virus replication

eg. Coronaviruses (include SARS virus)
RECOMBINATION - SOME USES



mapping by recombination frequency


mapping by marker rescue
RECOMBINATION - SOME USES

marker rescue
RECOMBINATION - SOME USES

mapping by recombination frequency
mapping by marker rescue
development of recombinant viruses for vaccines and therapeutic reasons
RECOMBINATION - SOME USES
raccoon eating bait with rabies vaccine in it
REASSORTMENT
REASSORTMENT
form of recombination (non classical)
very efficient
segmented viruses only
can occur naturally
used in some new vaccines
eg for influenza and rotaviruses
adapted fromTreanor JJ Infect. Med. 15:714
cold adapted

temperature-sensitive

attenuated

live vaccine

intranasal delivery

approved 2003

INFLUENZA VIRUS
NON-SEGMENTED NEGATIVE STRAND RNA VIRUSES
no classical recombination
no copy choice
no reassortment

least ability to exchange genetic material
other aspects of viral genetics
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
DEFECTIVE VIRUSES
lack gene(s) necessary for a complete infectious cycle
‘helper’ virus provides missing functions
DEFECTIVE VIRUSES
some examples of defective viruses

some retroviruses (use related helper)

hepatitis delta virus (uses unrelated helper)
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

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