12 - Mutation of viruses and its role in virus evolution

Question 1

What should be included in the topic?

Answer 1

• What is mutation?
• What is the cause of mutation?
• Types of mutation
• Forms of mutation
• Results of mutation
• Influences of the viral phenotype

Question 2

What is mutation?

Answer 2

• Independent changes in the genetic material
• The source of evolution
  
  • Opportunity for adaptation
  • Risk of loosing advantages / properties

Question 3

What is the cause of mutation?

Answer 3

• Failure in the nucleic acid replication
  
  • Cell: 10^-9
  • DNA viruses: 10^-5
  • RNA viruses: 10^-3
• Effective polymerase, but no proffreading activity

Question 4

Types of mutation

Answer 4

• Spontaneous
• Induced
  
  • Irradiation (UV, x-ray, atomic radiation)
  • Mutagenic drugs (halogenated uridine)

Question 5

Forms of mutation

Answer 5

• Point mutation
• Sequence mutation
• Substitutuion
• Insertion
• Deletion
• Inversion

→ Frame shift (a shift in codon sequence, e.g. if an extra amino acid added)

Question 6

Results of mutation

Answer 6

1. Silent mutation: no phenotypic change
   
   • Untraslated region
   • Redundant translation code
   • Not important amino acid
2. Lethal mutation:
   
   • Nonsense (stop)
   • Missense (amino acid change)
3. Conditionally lethal mutation:
   
   • Changes in the multiplication activity
     
     • I.e. thermo-sensitive mutants
4. Benificial mutants:
   
   • Rare
   • Accidental

Question 7

Influences on the viral phenotype

Answer 7

• Antigenic change:
  
  • Escape mutants
  • Influenza: antigenic drift
• Changes in host species specificity:
  
  • Feline panleucopenia → canine parvoenteritis
• Changes in organ specificity:
  
  • Equine herpes EHV 1 (abortion) ⟷ EHV 4 (rhinopneumonitis- lungs)
  • Infectious Bovine Rhinotracheitis IBR (rhinotracheitis) ⟷ IPV (vulvo-vaginitis)
• Different tissue tropism (cell cultures):
  
  • ​Bovine adenovirus (in kidney/testicular cells)
• Virulence variants:
  
  • _​_Newcastle disease
    
    • Lentogen strains
    • Mesogen strains
    • Velogen strains
  • Avian influenza:
    
    • Hemagglutnin protease cleavage site
• Cytophatic effect, plaque formation:
  
  • ​Aujeszky’s disease virus, BVDV
• Tempertaure optiumum:
  
  • ​Rhinoviruses, canine herpes virus
  • Rabies vaccine strains
• Evolution:
  
  • _​_Selective advatage
  • Environmental pressure
    
    • Adaption, niche
  • The virus evolution is a million times quicker than the host’s evolution
• Opportunity for protection:
  
  • Avirulent strains with conserved antigenic properties
    
    • Attenuated vaccine strains
  • Biotechnology, genetic engineering: accuracy
• Stabilization of virus strains:
  
  • _​_Protect from mutation - low passages
  • Seed virus, virus banks
  • Freezing drying, 4°C, (-20°C), -80°C, -196°C