DG

Micro- viruses

Core Structural Requirements for All Viruses

  • Nucleic-acid genome
    • Can be either DNA or RNA (never both)
  • Capsid (protein coat)
    • Assembled from capsomers; genetic economy forces extensive sub-unit repetition (e.g. Tobacco Mosaic Virus needs only 2 capsomer genes)
  • Spike proteins (= viral receptors)
    • Absolutely required; outer-most feature of every virion
    • If the virus is naked, spikes anchor directly to the nucleocapsid
    • If the virus acquires an envelope, spikes embed in that membrane
  • (Optional) Envelope
    • Animal-virus specific; stolen fragment of host phospholipid bilayer as the virion buds out
    • Greatly eases entry (fusion) but is extremely susceptible to dehydration, alcohol, detergents, simple soap & water

Canonical Viral Shapes (Morphologies)

  • Icosahedral
    • 20-sided geometric shell (think 20-sided die)
  • Helical
    • Spiral / rod-like nucleocapsid
  • Complex
    • Combination of icosahedral head + helical tail + tail fibers (all bacteriophages)
    • Only ONE complex animal virus: poxviridae (e.g. variola)
  • Envelope ≠ morphology (simply hides the underlying shape)

Bacteriophage “Molecular-Syringe” Anatomy & Significance

  • Icosahedral head → stores genome
  • Helical tail → conduit
  • Central tail fiber → pierces bacterial peptidoglycan to inject genome
  • Model used by Hershey & Chase to prove DNA is the heritable material

Host Range, Receptors & Tropism

  • Infection requires precise receptor–spike match
    • No receptor → no infection
  • Tropism = different host cells express different receptor sets
  • Specificity levels
    • Species: smallpox (humans only) vs rabies (most mammals except true rodents)
    • Tissue: Hepatitis B (hepatocytes only) vs measles (sialic-acid → nearly all cells → systemic)
  • Key receptors exam-worthy
    • HIV: CD4 and either CCR5 (macrophages) or CXCR4 (T-helpers)
    • SARS-CoV-2: ACE-2 (blood-pressure regulatory enzyme)
    • Sialic acid: influenza A, measles, RSV, rotavirus (drives high transmissibility)

Phage Survival Strategies (Genetic Models for All Virology)

  1. Productive
    • Lytic
      • New virions synthesized quickly → host lyses → acute disease, cell dies
      • Many low-mortality “common-cold” viruses, but also fatal rabies
    • Filamentous
      • Genome forms plasmid; host survives, continuously leaks virions
      • Analogous to chronic Hep B, HIV in humans
  2. Non-productive (Temperate / Lysogenic)
    • Integrase inserts viral DNA → prophage
    • Dormant through many divisions
    • Induction event → excision (imprecise) → lytic burst
    • Imprecise excision = lysogenic conversion / specialized transduction
      • Transfers virulence genes (botulinum, shiga, cholera toxins, etc.)

Simplified Classification Logic (skip Baltimore details)

  1. Genome: DNA vs RNA
  2. Strandedness: double vs single
  3. Envelope presence
  4. Symmetry optional (not required knowledge)
  • All RNA viruses must encode an RNA-dependent RNA polymerase (host lacks one)
  • Some package the polymerase, others synthesize it after entry

Replication Cycle of Animal Viruses

  1. Attachment = recognition (simultaneous event)
  2. Penetration
    • Enveloped: fusion (easy) or receptor-mediated endocytosis
    • Naked: endocytosis only
  3. Uncoating → capsid removed, genome free
  4. Synthesis
    • Hijack host ribosomes for structural proteins & immune evasion factors
    • Copy genome (nucleus for most DNA, cytoplasm for most RNA)
  5. Assembly
    • Spontaneous self-assembly when parts reach critical concentration
  6. Maturation
    • Proteolytic trimming / co-factor insertion to yield fully infectious particle
  7. Release
    • Enveloped: budding (acquires membrane + spikes)
    • Naked: host cell lysis

Acute vs Persistent Infections

  • Acute (lytic)
    • Rapid onset, high viral load, immune clearance or host death
  • Persistent
    • Chronic productive → constant release (Hep B, HIV)
    • Latent non-productive → silent, episodic reactivation (all herpesviruses)

Viral Oncogenesis – Three Mechanisms

  1. Insertional mutagenesis of proto-oncogene (HPV16/18)
  2. Chronic inflammation & regeneration (Hep C equilibrium in liver)
  3. Virus carries captured oncogene into new cell (rare, seen in retroviral fossils)

Major DNA Virus Families & Clinical Pearls

Adenoviridae

  • Naked, icosahedral; survives \approx 1 month on surfaces
  • Spectrum: respiratory disease, gastroenteritis, #1 cause of epidemic viral conjunctivitis
  • Vector for J&J COVID-19 vaccine

Polyomaviridae

  • Cause smooth mucosal polyps; low intrinsic oncogenicity
  • BK virus → 80 % kidney-graft failure (hemorrhagic cystitis/carcinoma) ⇒ mandatory donor screening
  • JC virus → progressive multifocal leukoencephalopathy in elderly leukemia patients
  • SV40: monkey virus that contaminated 1955-60 polio vaccine – prompted modern vaccine safety protocols

Papillomaviridae (HPV)

  • >150 types; most common viral STD in USA (~80\,\text{million} infected)
  • High-risk oncogenic strains: 16 & 18 (≈70\% cervical CA)
    • Low-risk wart strains: 6 & 11
  • Gardasil vaccines (recombinant VLP)
    • Bivalent (16,18) → Quadrivalent (6,11,16,18) → 9-valent (adds 5 more high-risk types)
    • \approx 99.999\% efficacy; given age 9–12 (pre-sexual) to all genders; limited utility >40 y due to prior exposure

Herpesviridae

  • Master of latency (integration in neurons)
  • Alpha group (epithelial entry → neuronal latency)
    • HSV-1 (oral) & HSV-2 (genital) – cross-infect; contagious \pm 3\text{–}7 days around sore; Valtrex shortens to \pm 1 day
    • VZV (HHV-3): childhood chickenpox → adult shingles (painful neural rash); live and subunit vaccines available
  • Beta group – Roseola (HHV-6/7) – mild
  • Gamma group
    • EBV (HHV-4): infectious mononucleosis; $$95