Viruses (L5)

• Classification of viruses


  • Morphology (size and Shape)
  • Chemical Composition & Structure of Genome
  • Mode of Replication
• Virion


  A fully assembled infectious virus
• Virus structure


  • Nonenveloped virus
  • Enveloped virus
• Enveloped virus


  • Outer membrane layer or "envelope" derived from host cells and incorporates both host and viral-specific antigens
  • Consists of lipid bilayer
  • Exterior of bilayer contains glycosylated membrane proteins
  • Virus envelopes can be considered an additional protective coat
  • Glycoproteins remain exposed as spikes which are essential for attachment
• Virus Morphology


  • Helical
  • Icosahedral
• Helical


  Identical protein subunits self-assemble into helical array surrounding nucleic acid (spiral path)
• Icosahedral


  Polyhedron have 20 equilateral triangular faces and 12 vertices
• Viral pathogenesis


  • Implantation of virus at entry site
  • Local replication
  • Spread to target organs
  • Shedding of virus into environment
• Factors affecting viral pathogenesis

  • Accessibility of virus to tissue
  • Cell susceptibility to virus multiplication
  • Virus susceptibility to host defences
• How a virus replicates

  1. Virus particle attaches to host cell

  2. Genetic instructions released into host cell

  3. Injected genetic material recruits host cell's enzymes

  4. Enzymes make constituents for more new virus particles

  5. New particles assemble into new viruses

  6. New viruses break free from host cell

  
• Vaccines


  • Many vaccines have been developed from attenuated live viruses
  • Recombination is being used to find new vaccines
• Anti-viral: Preventing uncoating of virus


  • Blocking of viral cellular membrane H+ ion channels (Amantadine)
  • Neuraminidase Inhibitor (Oseltamivir phosphate)
• Nucleotide analogues


  • Competitive inhibition of viral DNA polymerase utilization of GTP
  • Viral chain termination (guanosine analogue substitute)
  • Inactivation of DNA polymerase
• Swine Flu


  • Swine-origin influenza A (H1N1) virus (s-OIV)
  • Transmission by indirect, direct contact, inhalation of infectious droplets
  • Incubation ~ 1-4 days, infectious for 1-7 days from onset of illness onset or until symptoms resolve
  • Frequent symptoms: Fever, cough, sore throat, diarrhoea & vomiting, myalgia and joint pain
  • 2-6% need hospitalization
• Swine Flu Complications


  • Pneumonia and dehydration
  • Respiratory failure resulting from severe pneumonia and acute respiratory syndrome
  • Renal or multi-organ failure
• Swine Flu Antivirals


  • Oseltamivir: Neuraminidase inhibitor – prevents new virus release from infected cells
  • Zanamivir: Administered by inhalation, action similar to oseltamivir
• Swine Flu Resistance


  • Already resistant isolates detected due to mutations conferring resistance to neuraminidase enzyme
• Swine Flu Vaccines


  Already been made and are given to those at highest risk at contracting S-OIV
• Virus

  Sub microscopic entity consisting of a single nucleic (RNA or DNA) acid surrounded by a protein coat (capsid) and capable of replication only within the living cells of bacteria, animals or plants
• Characteristics of a virus

  • Infectious disease-causing agents
  • Reproduce only in living host cells
  • 20-250 nm
  • Core contains RNA or DNA within a protein/capsid shell
  • Carries only one or two enzymes which decode genetic instructions
• Measles virus

  Uses chick embryo cells
• German measles virus

  Uses monkey kidney cells
• Mumps virus

  Uses embryonated chicken eggs
• Polio virus

  Uses monkey kidney cells
• Yellow fever virus

  Uses chick embryo eggs
• Varicella-zosta virus

  Uses human embryo eggs
• Antiviral chemotherapy

  • Virucidal agents: directly inactivate viruses
  • Antiviral agents: inhibits viral replication at cellular level
  • Immunomodulatory: alter host immune response

  Can affect viruses at different points in their replicative cycle
• Potential sites for pharmacological treatment

  • Fusion inhibitors
  • Ion channel inhibitors
  • Polymerase inhibitors
  • Protease inhibitors
  • Neuraminidase inhibitors

  
• Fusion inhibitors: prevent attachment of virus
• Ion channel inhibitors: prevents uncoating of virus
• Polymerase inhibitors: stops replication of DNA/RNA
• Protease inhibition: causes new viruses to become inactive
• Neuroaminidase inhibitors: prevents release of virus from infected cells
• Amantidine

  • Stops penetration, uncoating and assembly of virus
  • Active against influenza A
• Acyclovir

  • DNA chain termination
  • Active against herpes simplex
• Ribavirin

  • Inhibition of 5’-capping of viral mRNA
  • Active against influenza A, B, C and measles virus
• Zidovudine

  • Inhibits reverse transcriptase
  • Active against HIV