July 1 recording

Review: Universal Viral Components

• Genome (one of four canonical types)

  • \text{dsDNA},\;\text{ssDNA},\;\text{dsRNA},\;\text{ssRNA}

• Capsid

  • Protein shell built from capsomeres (icosahedral, helical/filamentous, or complex)

• Nucleocapsid = capsid + enclosed genome

• Envelope (only in enveloped viruses)

  • Phospholipid bilayer “stolen” from previous host membrane; decorated with peplomers/spikes

• Peplomers (Spikes)

  • Viral ligands responsible for host-cell recognition and attachment

Other Viral Parts (not universal)

Stabilizing Proteins (non-enzymatic)

• Tegument proteins (e.g.0Herpesviridae)

• Matrix proteins (e.g.0Influenza A/B)

• Function: fill space between nucleocapsid & envelope, increase environmental stability (warm/moist surfaces, towels, bathwater, doorknob scenarios)

• Diagnostic inference: if tegument/matrix present → virus must be enveloped & slightly hardier than typical enveloped virus

Unique Viral Enzymes

Vocabulary Connections

• Virion – dormant extracellular particle

• Virus – active intracellular form directing synthesis

• Provirus – integrated viral DNA only (no capsid or envelope present)

Bacteriophage Architecture (Complex Capsid)

• Head (icosahedral) containing genome

• Contractile tail sheath + tail tube

• Baseplate with tail fibers (ligands) + lysozyme at tip

• Entire structure made of capsomeres despite different shapes/functions

Influenza vs. HIV Structural Highlights (application)

• Influenza A: 8 ssRNA segments, M matrix protein, H & N peplomers (“H1N1”, “H3N2” typology)

• HIV-1: ssRNA (×2), RT + Integrase + Protease, matrix protein p17, capsid p24, envelope with gp41 (stalk) & gp120 (tip) peplomers

Attachment (Adsorption / Adhesion)

• Principle: ligand–receptor specificity (key-and-lock); determines host range (species-, tissue-, cell-type specificity)

• Receptor Protein = host‐encoded membrane protein; Ligand = viral grabber

  • Bacteriophage: capsomeres on tail-fiber tips

  • Naked virus: capsomeres anywhere on capsid surface (e.g.0rhinovirus)

  • Enveloped virus: peplomers (spikes) (e.g.0SARS-CoV-2 S-protein binding ACE-2)

• Attachment Antagonists (entry inhibitors)

  • E.g.0Maraviroc (HIV CCR5 blocker); SelzentryAE – drugs that occupy receptor or ligand to block docking

Penetration / Entry Mechanisms

Bacteriophage (“Squat-&-Squirt”)

1. Tail fibers bind → baseplate presses against cell envelope

2. Lysozyme drills hole in peptidoglycan

3. Tail sheath contracts, injecting genome; empty capsid remains outside

Animal Naked Viruses

1. Endocytosis (Trojan horse)

   • Host engulfs protein-rich particle; vesicle formed

   • Uncoating: Host enzymes dissolve capsid → genome released

2. Direct Entry / Pore Formation

   • Capsomeres swivel to create pore; genome “dribbles” in; no uncoating required

   • Diagnostic: insensitivity to uncoating inhibitors

Animal Enveloped Viruses

1. Endocytosis + Uncoating (as above)

2. Direct Entry (rare; capsid/genome only)

3. Fusion (unique)

   • Viral envelope merges with host membrane; nucleocapsid delivered into cytoplasm

   • Requires later uncoating of nucleocapsid

   • Fusion inhibitors (e.g.0Enfuvirtide – FuzeonAE) block this step

Synthesis – Conceptual Framework

• Viral genome commandeers host transcription/translation machinery; host genes silenced or degraded

• Two mandatory outputs

  1. Genome copies (exact replicas)

  2. Proteins

  • Always: capsomeres (and if naked, those alone)

  • Envelope viruses: + peplomers ± matrix

  • Any virus that requires enzymes brings instructions for: RT, RdRP, Protease, Integrase, Lysozyme, etc.

• Template rules (refresh)

  • Central dogma: DNA \xrightarrow{rep.} DNA \quad DNA \xrightarrow{transcription} RNA \quad RNA \xrightarrow{translation} \text{Protein}

  • Reverse trans.: RNA \xrightarrow{RT} DNA

  • Complementarity: A \leftrightarrow T\;(U),\; G \leftrightarrow C

  • Positive-sense RNA (+): readable directly by 70 S/80 S ribosomes (start codon AUG at 5′ end)

  • Negative-sense RNA (–): complementary, non-readable → must be converted by RdRP into +RNA before translation

Life-Cycle Architectures

Lytic (Virulent)

1. Attachment

2. Penetration

3. Synthesis (immediate expression—DNA degraded; host resources hijacked)

4. Assembly (self-assembly of parts)

5. Release (lysis/budding)

Lysogenic (Temperate)

• Same as lytic but with an extra Integration step after penetration

  • Viral DNA + Integrase → insertion into host chromosome → provirus/ prophage

  • Genes silent until trigger → excision → enter lytic path

• Examples: VZV (chickenpox → shingles), HIV in T-cells/macrophages, many bacteriophages

Antiviral Drug Targets (examples; non-exhaustive)

• Attachment: Selzentry, Griffithsin (research)

• Fusion: Enfuvirtide/Fuzeon (HIV), Umifenovir/Arbidol (influenza/SARS-CoV-2)

• Uncoating: Amantadine, Rimantadine (influenza A M2 blocker)

• RT inhibitors: AZT, Tenofovir, Efavirenz (HIV)

• Protease inhibitors: Paxlovid (PF-07321332 + ritonavir), Indinavir, Saquinavir (HIV)

• RdRP inhibitors: Remdesivir, Favipiravir, Molnupiravir (COVID-19, Ebola)

• Integrase inhibitors: Raltegravir, Dolutegravir

• Release (neuraminidase): Oseltamivir/Tamiflu, Zanamivir

Diagnostic Reasoning Cues (Critical-Thinking Triggers)

• Virus has tegument → must be enveloped

• Virus carries RT but not RdRP → ssRNA retrovirus; needs DNA intermediate

• Virus uses lysozyme → bacteriophage; genome injected through cell wall

• Antiviral works as “uncoating inhibitor” → virus likely enters by endocytosis

• Presence of integrase alone → dsDNA or cDNA virus capable of provirus formation

Practice Labeling Exercise (in-class)

• Identified:

  • (A) peplomers

  • (B) envelope (phospholipid bilayer)

  • (C) nucleocapsid (whole purple) / capsid if asked exterior only

  • (D) capsomeres (individual purple spheres)

  • (E) genome (ssRNA, dsRNA, ssDNA, or dsDNA)

  • (F) tegument/matrix protein layer

• Application Q: Could this virus be easily transmitted via food? → No (enveloped even with stabilizers; still fragile vs. naked viruses)

Study Strategies & Resources

• Fill in the provided Attachment–Penetration–Synthesis–Assembly–Release comparison chart

  • Yellow-highlighted entries = universal statements across virus types

• Re-draw diagrams (bacteriophage, naked, enveloped) without notes

• Practice “if … then …” logic questions about enzyme presence & infection route

• Watch recommended textbook animations (fig. 13-8, 13-11, 13-12) repeatedly

• Use recorded walk-through for lytic/lysogenic synthesis drawings before submission

Ethical & Historical Connections

• Henrietta Lacks case (HeLa cells) – viral oncogene induced immortality; consent & profit controversies

• RT & HIV therapy: viral load measured via RT activity – highlights diagnostic relevance of unique enzymes

Key Numerical / Statistical Mentions

• HIV infection curve: exposure to infectiousness ≈ 6 h (illustrates “fast” life cycle)

• DAT exam fee \approx\$695 (side anecdote for dental-school aspirants)

Terminology Quick-Reference

• Capsomere, Capsid, Nucleocapsid

• Peplomer (Spike), Matrix/Tegument

• RT, RdRP, Protease, Integrase, Lysozyme

• Virion, Virus, Provirus (or Prophage in bacteria)

• Positive (+) sense RNA, Negative (–) sense RNA

• Attachment Antagonist, Fusion Inhibitor, Uncoating Inhibitor