• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
Viral Genetics
 

Viral Genetics

on

  • 1,540 views

 

Statistics

Views

Total Views
1,540
Views on SlideShare
1,540
Embed Views
0

Actions

Likes
2
Downloads
96
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    Viral Genetics Viral Genetics Presentation Transcript

    • VIRAL GENETICS
      • PATHOGENESIS
      • LIFE CYCLES
      • VACCINE DEVELOPMENT
      • DRUG RESISTANCE
      www.freelivedoctor.com
    • 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.” www.freelivedoctor.com
    • 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
      www.freelivedoctor.com
    • NATURE OF GENOMES
      • RNA or DNA
      • SEGMENTED OR NON-SEGMENTED
      www.freelivedoctor.com
    • GENETIC CHANGE
      • MUTATION
      • RECOMBINATION
      www.freelivedoctor.com
    • ORIGIN OF MUTATIONS
      • SPONTANEOUS
        • tautomeric form of bases
        • polymerase errors
      www.freelivedoctor.com
    • Tautomeric forms of bases most of time rarely www.freelivedoctor.com
    • 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)
      www.freelivedoctor.com
    • www.freelivedoctor.com
    • ORIGIN OF MUTATIONS
      • SPONTANEOUS
      • PHYSICALLY INDUCED
        • UV light , especially problem if no access to repair
        • X-rays
      • CHEMICALLY INDUCED
      www.freelivedoctor.com
    • TYPES OF MUTATION
      • POINT
      • INSERTION
      • DELETION
      www.freelivedoctor.com
    • PHENOTYPES
      • PHENOTYPE
        • the observed properties of an organism
      www.freelivedoctor.com
    • 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
      www.freelivedoctor.com
    • 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
      www.freelivedoctor.com
    • 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
      www.freelivedoctor.com
    • GENETIC CHANGE
      • MUTATION
      • RECOMBINATION
      www.freelivedoctor.com
    • RECOMBINATION
      • Exchange of information between two genomes
      www.freelivedoctor.com
    • RECOMBINATION
      • ‘ classic’ recombination
      common in DNA viruses www.freelivedoctor.com
    • COPY CHOICE RECOMBINATION +ve strand 2 +ve strand 1 www.freelivedoctor.com template switch
    • COPY CHOICE RECOMBINATION +ve strand 2 +ve strand 1 www.freelivedoctor.com -ve strand recombinant -ve strand recombinant +ve strand continues copying
    • COPY CHOICE RECOMBINATION + strand - strand + strand www.freelivedoctor.com - strand
    • COPY CHOICE RECOMBINATION + strand + strand www.freelivedoctor.com
    • Other methods recombination
      • Take advantage quirks in virus replication
        • eg. Coronaviruses (include SARS virus)
      www.freelivedoctor.com
    • RECOMBINATION - SOME USES
      • mapping by recombination frequency
      • mapping by marker rescue
      www.freelivedoctor.com
    • RECOMBINATION - SOME USES marker rescue TK mutant HSV TK - mt www.freelivedoctor.com TK - wt TK wt HSV TK - wt
    • RECOMBINATION - SOME USES
      • mapping by recombination frequency
      • mapping by marker rescue
      • development of recombinant viruses for vaccines and therapeutic reasons
      www.freelivedoctor.com
    • RECOMBINATION - SOME USES vaccinia virus vaccinia virus for use as rabies vaccine TK rabies G rabies G T K www.freelivedoctor.com
    • raccoon eating bait with rabies vaccine in it www.freelivedoctor.com
    • REASSORTMENT www.freelivedoctor.com
    • REASSORTMENT
      • form of recombination (non classical)
      • very efficient
      • segmented viruses only
        • can occur naturally
      • used in some new vaccines
        • eg for influenza and rotaviruses
      www.freelivedoctor.com
      • cold adapted
      • temperature-sensitive
      • attenuated
      • live vaccine
      • intranasal delivery
      • approved 2003
      adapted fromTreanor JJ Infect. Med. 15:714 INFLUENZA VIRUS www.freelivedoctor.com
    • NON-SEGMENTED NEGATIVE STRAND RNA VIRUSES
      • no classical recombination
      • no copy choice
      • no reassortment
        • least ability to exchange genetic material
      www.freelivedoctor.com
    • other aspects of viral genetics www.freelivedoctor.com
    • 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 www.freelivedoctor.com ts N wt M ts M wt N ts mutant 1 ts mutant 2
    • DEFECTIVE VIRUSES
      • lack gene(s) necessary for a complete infectious cycle
      • ‘ helper’ virus provides missing functions
      www.freelivedoctor.com package me! copy me! package me! copy me! genome
    • DEFECTIVE VIRUSES
      • some examples of defective viruses
        • some retroviruses (use related helper)
        • hepatitis delta virus (uses unrelated helper)
      www.freelivedoctor.com
    • 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
      www.freelivedoctor.com
    • PHENOTYPIC MIXING no changes in genome possibly altered host range possibly resistant to antibody neutralization www.freelivedoctor.com
    • PHENOTYPIC MIXING PSEUDOTYPE www.freelivedoctor.com