Viruses & Prions – Comprehensive Study Notes

Scope of Microbiology

• Disciplines commonly covered in introductory microbiology:
  • Bacteria
  • Algae
  • Fungi
  • Protozoa
  • Plants
  • Animals
  • Viruses (focus of this lecture)

Viruses vs. Living Organisms

• Working biological definition of life used in class: “anything made of cells.”
• Viruses are NOT alive because:
  • They are acellular; built from a protein shell (capsid) without a nucleus or other organelles.
  • Possess no autonomous metabolism; cannot ingest nutrients or generate energy.
  • Cannot replicate independently; must exploit a host cell’s machinery.
• Consequence: therapeutic targeting is difficult because drugs that kill or block them risk harming the host’s own cells.

Ancient Viral Footprint in Humans

• Between 40\text{–}80\% of the human genome consists of remnants of ancient viral infections that were incorporated into germ-line DNA over evolutionary time.
  • Highlights how pervasive viral–host interactions have been.

Structural Anatomy of a Typical Virion

• Capsid
  • Protein coat that encloses nucleic acid.
  • Replaces the role of a “nucleus” but should never be called one (prevents confusion with cellular life).
• Genetic core
  • May be DNA or RNA; single-stranded (ss) or double-stranded (ds); positive (+) or negative (–) sense.
• Spikes / Tail fibers / Attachment proteins
  • Protein protrusions specific for receptor binding on host cells.
  • Analogy: burr-type plant seeds that cling to clothing; virions “cling” to a matching host surface.
• Envelope (only in enveloped viruses)
  • Host-derived lipid bilayer surrounding the capsid.

How Viruses Attach and Enter

• Free-floating virions randomly contact cells in air, droplets or body fluids.
• Attachment proteins bind matching receptors → fast, highly specific docking.
• Some spikes are cell-type specific, explaining tissue tropism (e.g., hepatotropic, neurotropic).

Replication Strategy & Host Cell Destruction

1. Attachment (& entry) via spikes or tail fibers.
2. Disassembly → release of viral genome into cytoplasm or nucleus.
3. Hijacking of host ribosomes/enzymes to:
   • Transcribe/translate viral genes.
   • Assemble capsid proteins, spikes, and copies of the genome.
   • Host looks like a bin of Lego pieces: many separate viral parts produced first.
4. Self-assembly: parts fit together “IKEA-style.”
5. Release
   • Lysis (cell bursts) for non-enveloped viruses.
   • Budding for enveloped viruses.

• Result: host cell often dies; symptoms arise from cumulative loss of tissue function.

Dormancy (Latency) & Lifelong Infections

• Examples: Varicella-zoster (chickenpox → shingles), Herpes simplex.
• During latency the viral genome is present but:
  • Minimal/no gene expression.
  • No capsid production → nothing for immune system or drugs to “see.”
  • Resides inside host nucleus or cytoplasm until reactivated.

Why Antiviral Therapy Is Hard

• Viral diversity: DNA vs. RNA; ds vs. ss; + vs. – sense.
• Drugs must selectively block viral enzymes (polymerase, protease, integrase …) without harming host equivalents.
• Need very specific diagnosis: correct agent only stops the matching virus.
• Latent viruses have no metabolic activity → current antivirals cannot target them.

Immune Response & Vaccination

• Spikes, envelope fragments, or capsid proteins make good vaccine antigens because they are:
  • Accessible to antibodies.
  • Usually non-infectious if presented alone ("inert parts").
• Vaccine design logic:
  1. Isolate/engineer harmless viral surface proteins.
  2. Inject → immune system memorizes their shape.
  3. Future exposure → rapid neutralization.
• Challenge: spike mutations (e.g., SARS-CoV-2 variants) may evade antibodies; hence concern over “escape” mutants.

Baltimore Classification Snap-Shot

• Lecture excerpt emphasized Class I dsDNA viruses:
  dsDNA \xrightarrow{\text{transcription}} mRNA \xrightarrow{\text{translation}} \text{Protein}
• +ssRNA viruses can use their genome directly as mRNA:
  +ssRNA \longrightarrow \text{Protein}
• Key vocabulary
  • Transcription: making mRNA from DNA (or sometimes RNA → RNA).
  • Translation: ribosomes turn mRNA into protein.
  • tRNA: transports amino acids to ribosome; reads codons.
  • Genetic code: one amino acid per codon of 3 nucleotides.

Host Transcription & Translation Refresher

• Occurs in eukaryotic cells as:
  DNA{(nucleus)} \xrightarrow{\text{transcription}} mRNA{(nucleus \rightarrow cytoplasm)} \xrightarrow{\text{translation at ribosome}} \text{Protein}
• Ribosomes often bound to the rough endoplasmic reticulum (RER).

Interferon: Natural Antiviral Defense

• Cytokine released by infected cells.
• “Interferes” with neighboring cells’ ability to support viral replication (e.g., inhibits viral RNA synthesis, up-regulates antiviral proteins).
• Contributes significantly to why healthy individuals are virus-free most of the time despite constant exposure.

Prions (Brief Contrast)

• Infectious proteins, not viruses.
• Cause transmissible spongiform encephalopathies (e.g., Creutzfeldt–Jakob disease, bovine spongiform encephalopathy).
• Pathogenesis:
  1. Misfolded protein seeds conversion of normal brain proteins into the abnormal form.
  2. Aggregates deposit in neural tissue → sponge-like degeneration.
• Extremely small, can circulate in blood and cross the blood–brain barrier.
• Resistant to conventional sterilization; pose unique public-health risks.

Key Take-Home Points for Exams & Clinical Practice

• Viruses are acellular entities completely dependent on host cells for replication.
• Viral surface proteins (spikes, tail fibers) determine host range AND are prime vaccine targets.
• Latency explains lifelong infections and the difficulty of “curing” certain viruses.
• Accurate viral identification is essential before prescribing antivirals.
• Immune modulators (e.g., interferons) and vaccines remain front-line tools.
• Prions represent a distinct, non-nucleic-acid–based infectious paradigm.