Di truyen hoc virus

1 VIRAL GENETICS • PATHOGENESIS • LIFE CYCLES • VACCINE DEVELOPMENT • DRUG RESISTANCE 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.” 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 4 NATURE OF GENOMES • RNA or DNA • SEGMENTED OR NON-SEGMENTED 5 GENETIC CHANGE • MUTATION • RECOMBINATION 6 ORIGIN OF MUTATIONS • SPONTANEOUS – tautomeric form of bases – polymerase errors 7 Tautomeric forms of bases most of time rarely 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) 9 10 ORIGIN OF MUTATIONS • SPONTANEOUS • PHYSICALLY INDUCED – UV light , especially problem if no access to repair – X-rays • CHEMICALLY INDUCED [...]... or ts N mutants which can complement are generally in different genes 34 DEFECTIVE VIRUSES • lack gene(s) necessary for a complete infectious cycle • ‘helper’ virus provides missing functions package me! package me! copy me! copy me! 35 DEFECTIVE VIRUSES • some examples of defective viruses – some retroviruses (use related helper) – hepatitis delta virus (uses unrelated helper) 36 ... rescue • development of recombinant viruses for vaccines and therapeutic reasons 26 RECOMBINATION - SOME USES 27 raccoon eating bait with rabies vaccine in it 28 REASSORTMENT 29 REASSORTMENT • form of recombination (non classical) • very efficient • segmented viruses only – can occur naturally • used in some new vaccines – eg for influenza and rotaviruses 30 INFLUENZA VIRUS • cold adapted • temperature-sensitive... two genomes 17 RECOMBINATION ‘classic’ recombination common in DNA viruses 18 COPY CHOICE RECOMBINATION template switch 19 COPY CHOICE RECOMBINATION continues copying 20 COPY CHOICE RECOMBINATION 21 COPY CHOICE RECOMBINATION 22 Other methods recombination • Take advantage quirks in virus replication – eg Coronaviruses (include SARS virus) 23 RECOMBINATION - SOME USES • mapping by recombination frequency...TYPES OF MUTATION • POINT •INSERTION •DELETION 11 PHENOTYPES PHENOTYPE – the observed properties of an organism 12 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... fromTreanor JJ Infect Med 15:714 NON-SEGMENTED NEGATIVE STRAND RNA VIRUSES • no classical recombination • no copy choice • no reassortment – least ability to exchange genetic material 32 other aspects of viral genetics 33 COMPLEMENTATION Interaction at the functional level, NOT the nucleic acid level ts mutant 1 ts mutant 2 Progeny virus assembled using wt N and wt M proteins Genomes in progeny are . RNA viruses can achieve in a single human generation.” 3 VIRAL GENETICS • VIRUSES GROW RAPIDLY • A SINGLE PARTICLE PRODUCES A LOT OF PROGENY • DNA VIRUSES. 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)