Virology Notes

Acellular Entities: Viruses

  • Moving from the discussion of living organisms (prokaryotes and eukaryotes) to acellular entities, primarily viruses.
  • Viruses along with other things are acellular.

Viruses: Intracellular Parasites

  • Viruses are intracellular parasites, residing inside cells.
  • Distinction from bacteria or fungi: Viruses are not alive and lack their own cells.
  • They are inert particles outside cells.

Viral Structure

  • Basic viral structure:
    • Genetic information (DNA or RNA).
    • Protein coat.
    • Some viruses possess a lipid layer (envelope).
  • Viruses are inert outside of cells: no metabolism, replication, or motility.
  • Upon entering a cell, viruses take over cellular functions to replicate.
  • Viruses use the host cell's machinery for replication.

Types of Viruses

  • Categorization based on host:
    • Prokaryotes.
    • Eukaryotes.
  • Viruses infecting prokaryotic cells are called bacteriophages.

Size of Viruses

  • Viruses are generally very small.

    • Smallest: Around 10 nanometers.
    • Largest: Around 1,000 nanometers (1 micrometer, similar to bacterial size).

  • Most viruses fall in the 20-250 nanometer range.

  • Generally, viruses are 10 to 100 times smaller than bacteria.

  • Examples:

    • Poliovirus.
    • Flu virus.
    • Smallpox virus.

  • Comparison to macromolecules: Viruses larger than lipids and proteins, smaller than bacteria.

Viral Components

  • Virus particle: Can be referred to as a virus or virion.
  • Core components:
    • Nucleic acid (RNA or DNA).
    • Protein coat.
  • Some viruses have a lipid layer outside the protein coat, called an envelope.
  • Enveloped vs. Naked Viruses:
    • Enveloped viruses have an outer envelope.
    • Naked viruses lack an envelope.
  • Hand sanitizers effective against enveloped viruses (targeting the membrane) but not naked viruses.
  • Genome: Either DNA or RNA, but not both.
  • Classification: Viruses classified as DNA or RNA viruses based on their genome type.
  • DNA or RNA can be double-stranded or single-stranded.
  • Replication depends on whether the viral DNA or RNA is single or double stranded, influencing how viruses replicate.
  • Attachment structures:
    • Tails in bacteriophages.
    • Spike proteins (on naked or enveloped viruses) for attachment.
    • Spikes are required for attachment to host cells.

Viral Shapes

  • Three general shapes:
    • Helical: Protein arranged in a spiral, rod-shaped.
    • Icosahedral: Three-dimensional geometric shape.
    • Complex structures: Features of both or neither helical/icosahedral.
  • Shape is independent of envelope presence: Enveloped or naked viruses can have any shape.
  • Shape determined by the arrangement of proteins.
    • Helical: Protein laid down in a helix, spiral, rod-shaped.
    • Icosahedral: Rhinovirus example of respiratory infection.
    • Complex: Poxvirus example.

Classification of Viruses

  • Viruses are classified based on what they infect and their genome.
  • Classified on whether they are:
    • Double-stranded DNA.
    • Single-stranded DNA.
    • Double-stranded RNA.
    • Single-stranded RNA.
  • Classification also considers:
    • Host infected.
    • Shape of the virus.
    • Type of disease caused.
  • Examples:
    • Enterovirus (polio).
    • Rhinovirus (common cold).
    • Papillomavirus (HPV, linked to cancers).
    • Rubella.
    • Influenza (flu).
    • Lyssovirus (rabies).
  • Family names end in "-viridae."
    • Example: Ebola in the Filoviridae family.
    • Coronavirus (COVID-19) in the Coronaviridae family.
  • Genus names end in "-virus."
  • Species names often the disease name.
  • Informal classification:
    • Enteric viruses: Cause gastrointestinal issues, spread via the fecal-oral route.
    • Respiratory viruses: Infect via the respiratory route and cause respiratory symptoms.
    • Zoonotic viruses: Transmitted from non-human animals to humans.
    • Arboviruses: Transmitted via arthropods like mosquitoes.
  • Informal names are not family names.

Bacteriophages: Viruses Infecting Prokaryotes

  • Bacteriophages: "Eaters of bacteria."
  • Relationships with host:
    • Virulent or lytic phages: Cause cell death upon release.
    • Temperate phages: Can become part of the host chromosome.

Lytic Cycle (Virulent Phage)

  • Example: T4 virus (T-even viruses) infecting E. coli.
  • Steps:
    • Attachment: Tail fibers attach to bacterial cell.
    • Penetration: Viral DNA injected into the cell.
    • Biosynthesis: Host DNA degraded, virus directs replication of its DNA and proteins.
    • Maturation: Assembly of viral particles.
    • Lysis: Viruses break out of the cell, killing it.
  • Detailed steps:
    • Attachment: Tail fibers exploit receptors on the bacteria.
    • Entry (Penetration): Lysozyme breaks down the cell wall, tail contracts, injecting genome.
    • Biosynthesis: Genome copies, protein production, degradation of host DNA.
    • Assembly (Maturation): Phage particles assemble.
    • Release: Lysozyme production, cell bursts, releasing ~200 new viral particles (burst size).

Lysogenic Cycle (Temperate Phage)

  • Example: Lambda (λ) phage.
  • Steps differ after penetration:
    • Attachment and penetration occur.
    • Viral DNA integrates into host genome.
    • Integrated DNA = prophage (phage DNA incorporated into host).
    • Replication occurs as cell divides, prophage passed to daughter cells.
    • Under stress, prophage excises and enters the lytic cycle.
  • Detailed steps:
    • DNA integrates at a specific site (non-homologous).
    • Prophage just "chills out" during good times.
    • Under bacterium stress (SOS signal, DNA damage), protease is activated, which destroys repressor, then resulting in DNA excision.
    • Then phage escapes the damaged host.
  • Lysogen: Bacterium with prophage.
    • Immune to infection by the same type of virus.
    • However, lysogen could have also undergone lysogenic conversion.
  • Lysogenic conversion: Virus contains toxin exampled by:
    • Corynebacterium diphtheriae: Produces diphtheria toxin.
    • Clostridium botulinum: Produces botulism toxin.
    • Specific E. coli strain (O157:H7): Shiga toxin -> bloody diarrhea, hemolytic uremic syndrome.
  • Toxins increase viral spread.

Bacteriophages and Horizontal Gene Transfer - Transduction

  • Generalized transduction: Packaging error during lytic cycle.
    • Host DNA accidentally packaged into virus.
    • Movement of DNA without infection.
  • Specialized transduction: Mistake during excision in the lysogenic cycle.
    • Infection by virus.
    • Formation of prophage (phage DNA integrates into host).
    • Improper excision results in flanking DNA being taken out.
    • Results in Defective viral particle can lead to homologous recombination.
    • New viral particle is defective and then contains bacterial DNA.
    • Only host DNA right next to viral DNA can be moved.

Studying Bacteriophages in the Lab

  • Viruses multiply inside living cells.
    • Cultivation done inside bacteria.
    • Plaques are visualized (areas of death).
    • Plaques can be counted which can be used to estimate phage quantity.
    • Grown on bacterial lawn.
    • Blue represents bacterial growth.

Purple represents holes in plaques (areas of bacteria that have been lysed)

  • Represents the number of viruses in the dealing with.

Animal Viruses: Replication Cycle

  • Similarities to bacterial viruses but also differences.
  • Attachment: Receptors (glycoproteins) on the plasma membrane.
  • Often requires more than one receptor -> specificity.
  • Attachment is looking at HIV and the need of binding to its host cell.
  • Limits range of cells or organisms that can be infected.
  • Example: HIV needs two receptors to bind with cell. the necessity of two receptors means that only certain immune cells are infected
  • Penetration:
    • Entire genome and protein coat enter the cell.
    • Enveloped viruses fuse with the membrane or enter via endocytosis.
  • Uncoating: Genome released from the protein coat.
  • Synthesis: More complex than in bacterial viruses.
  • Replication strategy differs based on genome type (DNA, RNA, reverse transcribing).
  • Multiple copies of genome and viral structures made.

Synthesis: DNA Viruses

  • Usually straightforward, occurring in the nucleus.
  • Double stranded DNA virus: the DNA is copied and goes through transcription and translation.
  • Single stranded DNA virus: the single strand copies and turns into a double strand and then is transcribed and translated.
  • All happens by taking over mechanisms of the cell.

Synthesis: RNA Viruses

  • Single stranded RNA or double stranded RNA.
  • No DNA involved; RNA used to make protein.
  • Virus must copy its genome.
    • Animal cells cannot copy single-stranded RNA.
    • Virus brings its own RNA polymerase for genome copying which allows copying of that genome.
    • Enzymes lack proofreading ability -> mutations -> rapid evolution.
  • Some RNA viruses reassort (antigenic drift and shift).
    • Antigenic drift: Slow change over time.
    • Antigenic shift: Major changes creating new flus (bird flus).

Synthesis: Reverse Transcribers

  • Examples: HIV, RNA virus.
  • Viral RNA converted to DNA using reverse transcriptase.
  • Viral DNA integrates into host genome (provirus).
  • Provirus cannot be eliminated.
  • Prevented using HIV drugs (prevents release and accumilation of new viruses).
  • Reverse transcriptase:
    • RNA to DNA
      • Reverse transcription.
        *Not naturally happening in cells (carried by the virus).
  • The reverse transcriptase turns viral RNA into viral DNA.

Assembly and Release

  • Assembly: Viral particles assembled.
  • Release:
    • Budding (enveloped viruses). The viruses acquires its envelop from organelles.
    • Naked viruses: Released when the host cell dies.