MIC 401 Unit

• Basic building blocks of a virus

  • Capsid (helical or icosahedron)
  • Envelope (phospholipid bilayer)
  • Nucleic acid (+ ssRNA, - ssRNA, dsRNA, dsDNA, ssDNA)
• + ssRNA


  Can make own proteins independently
• Structure of a virus particle

  • Protection of fragile nucleic acid genome
  • Specificity for host recognition and interaction
  • Delivery of genome into host cell
• Virus replication cycle


  1. Virion binds to host

  2. Enter cell

  3. Virion released into cytoplasm

  4. Replication transcription complex

  5. Mature virion assembly

  6. Virion exocytosis
• Antigenicity


  Ability for specific recognition by T cells receptor or antibody due to immune response
• Immunogenicity


  Ability of substance to induce adaptive immune response
• Plaque assay


  • Measures number of infectious/cytotoxic viruses

  - process= grow virus, put virus on agar so virus NOT spread out and only infects neighboring cells. Holes/plaques form to show where infected cells were killed by the virus
• pfu (plaque forming units)


  Measure of number of infectious virus particles
• MOI (multiplicity of infection)


  Average number of virus particles infecting each cell
• IC50


  Inhibitory concentration at 50% when doing dilution series curve, measures drug's potency and ability to inhibit a biological process
• Multiplexing


  Use antibodies to stain plaques and look at them with microscope and count them on computer
• HDV and HBV


  HDV is satellite virus that uses HBV's spike protein to get inside cell, HDV is not infectious without co-infection with HBV
• Hepatitis viruses with vaccines and treatments

  • Vaccines: HAV, HBV, HDV
  • Treatments: HCV
• Hepatitis virus transmission routes

  • Enteral and fecal/oral (HAV, HEV)
  • Parenteral (bloodborne) (HBV, HDV, HCV)
• HAV and HEV can exist in enveloped and non-enveloped forms
• HBV has partially dsDNA and partially ssDNA, uses reverse transcriptase
• HDV is a satellite virus that uses HBV's spike protein
• HBV and HDV co-infection can cause fulminant and very fatal hepatitis
• Hepatitis symptoms


  • Appetite loss
  • Fatigue
  • Low grade fever
  • Muscle and joint pain
  • Nausea
  • Vomiting
  • Jaundice
  • Liver inflammation
  • Brain damage
  • Stroke
  • Psychological issues
• Hepatitis diagnosis uses IgM and IgG, and elevated liver enzymes (ALT) in blood
• HA (hemagglutinin)


  Binds to sialic acid, mediates membrane fusion
• NA (neuraminidase)


  Glycoside hydrolase that releases virus particles after maturation and breaks down mucins
• Antigenic drift


  Slow change in genome due to error-prone RNA dependent polymerase, results in seasonal flu requiring new vaccine
• Antigenic shift


  Rapid change in genome due to gene reassortment, results in epidemics and pandemics
• Glycans


  Used for influenza binding, sialic acid residues have different sugar linkages for human vs avian influenza
• Transcriptional polarity


  Negative sense convert to positive sense mRNA

  • After each gene transcribed, RNA-dependent RNA polymerase STOPS in intergenic region to release the new mRNA

  * at every intergenic region, polymerase will either fall off or stay on

  • If fall, must reenter genome at the leader sequence and start over

  * If NOT come off, then will make next mRNA in gene sequence

  • result= farther downstream genes are less transcribed

  • Nucleocapsid protein greater amount than L protein
• Differences between orthomyxoviruses and paramyxoviruses

  • Orthomyxoviruses have 8 segment genome, paramyxoviruses have non-segmented genome
• Paramyxoviruses (mumps, measles) cause profound but rare hearing loss, have effective vaccines, and lifelong immunity
• R0 (basic reproductive number)


  Number of people that 1 sick person will infect that are not vaccinated and have not had previous infection
• Measles has the highest R0 of all viruses at 12-18
• Factors that make measles highly infectious: can remain airborne for 2 hours, very low infectious dose, aerosolized as cough, infects lung epithelia and hijacks immune cells
• Episomal latency


  Viral genes stabilized and floating in nucleus/cytoplasm as distinct objects
• Proviral latency


  Viral DNA integrates directly into host cell genome
• Papillomavirus life cycle


  Infect basal cells, establish and maintain genome, induce proliferation, amplify genome, package virion, release from cell
• HPV must infect basal layer cells as they are growing and replicating
• L1 protein


  Self-assembles into empty capsids, basis for HPV vaccines
• E6 and E7 proteins


  Degrade p53 and Rb, leading to cancer development
• Advantage for HPV is to make more virus and eventually cause cancer
• Polyomavirus spread and reactivation


  1. Inoculate and multiply in respiratory tract, 1st viremia, multiply in kidney, transient 2nd viremia

  2. Reactivate in immunodeficient individuals to cause BK viruria/hemorrhagic cystitis or JC viremia/PML
• Virobiota


  Viruses that are stable and part of normal microbiota in humans, can give evolutionary advantages to bacteria and perturb immune system