Virology (2024, Columbia Universtiy)

Lectures of Vincent Racaniello

Lecture 1

  • Viruses are everywhere
  • Viral genomes are a part of our own genetic material
  • The numbers of viruses on Earth is staggering
  • The vast majority of viruses that infect us have little to no impact on our health or wellbeing
    • Just passing through e.g. pepper mild mottle virus
    • Beneficial viruses
    • We have an amazing immune system
  • Viruses shape host populations and vice-versa
  • Virology is an integrative science
  • Lots of people who don’t know what they are talking about weigh in on virology – hopefully not me in future!
  • Definition: an infectious, obligate intracellular parasite comprising genetic material (DNA or RNA), surrounded by a protein coat, sometimes a membrane
  • When we study viruses, we must also learn something about the host too
  • Viruses have two phases: virion, infected cell
  • …are passive agents! Do not anthropomorphise
  • …are very small! (There are also “giant” viruses)
  • …replicate by assembly of pre-formed components into many particles
  • Virus classification by nucleic acid
    • Kingdon, phylum, class, …
  • Barely sampling anything out there! Tonnes of viruses to discover
  • Two key facts
    • All viral genomes are obligate molecular parasites that can only function after they replicate in a cell
    • All viruses must make mRNA that can be translated by host ribosomes

Lecture 2

  • Virologists like to divide the infectious cycle up into steps but there are no real clear boundaries
  • Cells can be
    • Susceptible: functional receptor for given virus
    • Resistant: no receptor
    • Permissive: capacity to replicate virus
    • Must be susceptible and permissive to take up virus particle and replicate it
  • “Passage” or “passing” can select for properties (evolution)
  • Growing cells in culture! Nobel prize, 1954
  • “Monolayer”: layer of one cell thickness (of cells)
  • Cell line: live forever
  • Cytopathic effects: structural changes in host cells that are caused by viral invasion.
    • Formation of syncytia
  • How many viruses in a sample?
    • Measure infectivity
    • Measure physical (virus particles and their components)
  • Plaque assay (plaque forming units [PFU] per ml). Nobel prize, 1975
    • TNTC (too numerous to count)
    • Getting the right number of dilutions
    • One-hit and two-hit kinetics
  • Not all virus particles are infectious!
    • Particle / PFU ratio can be 1-10,000
    • Damaged particles, mutations, complexity of infectious cycle
    • Complicates study of viruses!
  • One-step growth cycle
    • Adsorb, dilute culture, sample, assay
  • How many viruses each cell gets is approximately Poisson
    • MOI of 10 then you’d get a single burst of virus release: every cell infected in sync
  • Physical methods for detecting viruses include hemagglutination, serological techniques, polymerase chain reaction, and high-throughput sequencing
    • PCR is not the same as infectious virus. PCR positivity lasts much longer than infectiousness!

Lecture 3

  • The viral nucleic acid genome is the genetic code