9 - General features of virus multiplication

Question 1

Give the multiplication cycle of viruses

Answer 1

1. Adsorption (attachment to the host cell)
2. Penetration (entry into the host cell)
3. Decapsidation (nucleic acid release)
4. Eclipse (expression of the genetic information)
   
   1. Transcription, translation and nucleic acid replication
5. Maturation (assembly of progeny virions)
6. Release (evacuation from the host cell)

• 10² – 10⁶ virion/cell
  
  • → new cells, new cycles
    
    • → log phase

Question 2

1. Adsorption

Answer 2

• Triggered by host cell
• Cell surface receptor: (stable)
  
  • Genetically coded, eg:
    
    • H19 chromosome → poliovirus
    • H3 chromosome → HSV
  • Usually already expressed in the embryo
  • Necessary for cellular functions
• Virus surface antireceptor: (more variable)
  
  • Viruses adapt the cellular surface receptors during their evolution
  • Related viruses usually target the same cell surface receptor
  • Sometimes non-related viruses have the same receptor (ie. CAR = coxackie-adeno receptor)
  • → specificity - determined by the tissue or species receptor protein
• Receptor, antireceptor are negatively charged → repulsion, collision by chance
  
  • Reversible connection → cations neutralize the electrostatic power
  • Irreversible connection → chemical bonds between the proteins

Question 3

2. Penetration

Answer 3

• Energy dependent
  
  • ​Needs 4x activation energy than adsorption
  • Only in living cells
  • Only over +4ºC
• General forms:
  
  • Translocation
    
    • ​Eg. picornavirus
    • “Trapdoor” mechanism
    • Allows virus into cell
  • Endocytosis
    
    • ​In most non-enveloped viruses + herpes and pox
    • Cell nutrition endosome → phagolysosome → decapsidation
  • Membrane fusion
    
    • ​Only in enveloped viruses
    • Viral fusion (F) protein induces
    • The viral envelope merges into the cytolasmic membrane of the host cell → only the nucleocapsid gets into the cytosol
• Alternaltive forms:
  
  • Injection
    
    • ​Tailed bacteriophages
    • Lysozyme enzyem + contractile proteins
  • Sexfimbria
    
    • ​Ribophages
    • Lack of cellular wall → “bacterial sexual disease”
  • Pasive
    
    • ​Plant viruses
    • Cellular wall injuries, arthropod bites

Question 4

3. Decapsidation

Answer 4

• Release of nucleic acid from the capsid
• Dangerous for the virus, but necessary for the transcription
• Strategies:
  
  1. Use of cellular proteases (in lysosomes)
  2. Viral uncoating proteins (ie. poxviruses)
  3. Partial decapsidation
     
     • Hiding the nucleic acid until the early virus protein production (ie. DNA viruses in the nucleus, reo, orthomyxo, paramyxoviruses)
  4. Sometimes simultaneous penetration and decapsidation (ie. by translocation, injection)

Question 5

4. Eclipse

Answer 5

• The expression and copy of the viral genetic information (see topic 10)
  
  • Transcription (mRNA)
  • Translation (viral protein prod’n)
  • Nucleic acid replication
• Different strategies according to the type of the nucleic acid → the Baltimore-system

Question 6

4. Maturation

Answer 6

• Polypeptides → proteins
• Glycolysation, dimer formation, antigen development
• Occurs usually in ER or Golgi

Virus assembly

• Usually at the site of replication → protection
  
  • In cytoplasm: RNA viruses, Pox, asfarviridae
  • In nucleus: other DNA viruses
• Nucleic acid signals → connects to the capsomers
• Mistakes are frequent (70% viruses are incomplete virons)
• Methods:
  
  • The nucleic acid enters into the capsid: icosahedral
  • The capsomers surround the nucleic acid: helical
• Scaffolding proteins regulate the assembly
• Envelope and matrix proteins are acquired from cellular membranes

Question 7

5. Virus release

Answer 7

• Passive or active
• Non-enveloped virus → cytolysis
  
  • Rapid: Picornav virus
  • Slow: Parvovirus
  • Apoptosis: Adenoviridae
• Enveloped virus
  
  • Budding
    
    • Rapid: Togavirus
    • Slow: Arenavirus
• Budding site is virus specific
  
  • Nuclear membrane: Herpesvirus
  • ER: Flavirus
  • Golgi: Coronavirus, bunyavirus
  • Cytoplasmic membrane: Asfarvirus, togavirus, orthomyxovirus, paramyxovirus, rhabdovvirus,
• Cell-associtated viruses: gammaherpesvirinae (release at cell death or injuries)
• Cell fusion → membrane tunnels
  
  • Safe way of spreading (herpesvirus, paramyxovirus)
• Alternaltive forms of virus release:
  
  • Lysosome disitegrations (herpesviridae)
  • T bacteriophages: lysozyme enzyme digests the cellular wall
  • Plant cells are firmly connected to each other
    
    • → viruses spread from cell to cell
    • → mosaic pattern