[5] Maturation

• Assembly of viruses is dependent on host cell machinery
• General Steps

  1. Protein synthesis to form the protein shell
  2. Assembly
  3. Packaging of genome within virion
  4. Acquisition of lipid bilayer
  5. Exit/Release from host cell
  6. Maturation of virus particles
• Proteins can be post translationally translocated through ER membrane or free ribosomes diffusing through the cytoplasm
• Glycosylated proteins need to enter through the secretory pathway
• Nothing happens via free diffusion

  • Cell makes use of transport systems
• Assist to correct folding of proteins

  Chaperone proteins
• Responsible for binding to the cellular receptor protein in Influenza

  Hemagglutinin
• Hemagglutinin is a glycoprotein
• Viral genomes can encode their own chaperone protein
• Diffusion is often random

  1. ATP dependent movement via motor proteins is required
• • Short distances - across nuclear pores / membranes
  • Long distances - site of genome synthesis to site of assembly

  
• Nuclear inclusions bodies are high concentrations of viral NA

  • Nuclear inclusions and cytoplasmic inclusions
  • Allows for more efficient assembly
• Assembly line strategy:

  1. Structures are synthesized in a separate and discrete manner
  2. Sub particles are first made then joined together
• Types of assembly:

  1. Sequential step by step assembly line
  2. Para sequential
• Sequential step by step assembly line

  • Ensures quality control
  • Increases efficiency

  Para sequential

  • Done all together, not step by step
  • Nucleocapsid packaged inside the nucleus
  • Matrix proteins imported back into nucleus
  • Synthesis of glycoproteins while genome is packaged
• Strategies of Viral Structural Unit Assembly

  1. Assembly from individual protein Molecules
  2. Polyprotein precursor
  3. Chaperone proteins / proteases
• Assembly from individual protein molecules

  • Synthesis of individual protein molecules
  • Noncovalent interactions form into multisubunit virus-protein structure

  Polyprotein precursor

  • All of the subunits are synthesized as a polyprotein
  • Folds correctly

  Chaperone proteins / proteases

  • Finalize the final subunit
  • Some chaperones assist assembly
  • Chaperones may be cellular or viral encoded genes
• Virus Like Proteins:

  1. Assembled viral proteins that are not infective
  2. Do not have genetic material
  3. Used as vaccine component, produces high antibody levels
• VLPs are produced for:

  1. Structurally simple non-enveloped viruses
  2. Structurally complex viral capsids with multiple protein layers
  3. Viruses with lipid envelopes
• Polyomavirus, Adenovirus, Influenza Assembly

  1. Needs correct nuclear localization signals
  2. Localization to the plasma membrane
• Genome packaging signals

  • Very important to only pack viral nucleic acids
  • NA sequences can interact with capsid proteins so they can be inserted
• Herpes virus is tightly packed, viral genome is under very high pressure
• Interaction of viral proteins at the plasma membrane is responsible for budding process

  • Nucleocapsid -> Matrix proteins -> Viral proteins on host membrane
  • Envelope proteins required for budding
• Semiki forest virus assembly strategy

  • Viral chromosomes being synthesized
  • Capsid proteins form the procapsid structure
  • Directed to plasma membrane
  • Interaction with the viral envelope proteins
  • Budding

  
• Influenza virus budding:

  1. From apical side of respiratory tract
  2. Matrix proteins interact with glycoproteins to facilitate budding
  3. Only membrane proteins are responsible for budding of the virus
• Complex strategies from viral membrane acquisition:

  1. Herpes Strategy 1
  2. Herpes Strategy 2
  3. Vaccinia virus