RNA Viruses: Orthomyxoviruses

Orthomyxoviruses: Basics & Structure - Flu's Inner Secrets

• Family: Orthomyxoviridae; Influenza viruses A, B, C.
• Genome: Segmented (7-8 segments), single-stranded, negative-sense RNA (-ssRNA).
  • Allows genetic reassortment (antigenic shift).
• Structure: Enveloped, spherical/pleomorphic (80-120 nm).
  • Hemagglutinin (HA): Glycoprotein spikes; attachment to sialic acid receptors, fusion.
  • Neuraminidase (NA): Glycoprotein spikes; release of progeny virions, cleaves sialic acid.
  • M1 protein: Matrix protein; structural integrity.
  • M2 ion channel (Influenza A): Uncoating; target for amantadine/rimantadine.
  • RNA polymerase complex (PA, PB1, PB2): Inside virion.
• Replication: Nucleus (unique for RNA viruses, except retroviruses).

⭐ Antigenic Shift: Major genetic reassortment in segmented genomes (e.g., Influenza A) leading to pandemics. Occurs when a cell is co-infected by two different strains. (📌 Mnemonic: Shift = Sudden, Severe, Segmented genome effect).

Orthomyxoviruses: Replication & Variation - Shape-Shifting Menace

• Replication Highlights:

  • Unique nuclear replication (for an RNA virus).
  • "Cap snatching": viral endonuclease steals 5' cap from host mRNA for viral mRNA synthesis.
  • Uses viral RNA-dependent RNA polymerase.
  • Assembly at cell membrane; release via budding.

• Antigenic Variation:

  • Antigenic Drift:
    • Minor changes in HA (Hemagglutinin) & NA (Neuraminidase) genes via point mutations.
    • Causes epidemics (Influenza A, B, C).
  • Antigenic Shift:
    • Major changes, creating new subtypes via genetic reassortment of 8 RNA segments.
    • Requires co-infection (e.g., human + avian/animal strains in a single host cell).
    • Causes pandemics (Influenza A only).
    • 📌 Shift = Sudden, Severe, Segment Swapping.

⭐ Orthomyxoviruses (e.g., Influenza) uniquely replicate in the host cell nucleus, unlike most other RNA viruses (exception: Retroviruses).

Orthomyxoviruses: Influenza - Fever, Chills, Spills

• Clinical Presentation: Sudden onset of:
  • Fever (high, 38-40°C), chills
  • Myalgia (muscle aches), malaise (general discomfort)
  • Headache, sore throat, non-productive cough
  • "Spills" refers to respiratory secretions.
• Pathogenesis:
  • Transmission: Respiratory droplets.
  • Replicates in respiratory epithelium, causing cell damage & inflammation.
  • Incubation period: 1-4 days.
• Complications:
  • Primary viral pneumonia.
  • Secondary bacterial pneumonia (e.g., S. pneumoniae, S. aureus, H. influenzae).
  • Myositis, myocarditis, pericarditis (rare).
  • Neurological: Encephalopathy, Guillain-Barré syndrome.
  • Reye's syndrome: ⚠️ Aspirin use in children with influenza/varicella.

⭐ Reye's Syndrome: Characterized by fatty liver degeneration and acute encephalopathy; strongly associated with aspirin use during viral illness in children.

📌 Mnemonic: FLU = Fever, Lethargy, Unwell (aches, cough).

Orthomyxoviruses: Diagnosis & Management - Flu Fighters' Toolkit

• Diagnosis:
  • Clinical; lab for public health/severe cases.
  • RT-PCR: Gold standard. Detects RNA; high sens/spec. Differentiates A/B, subtypes (H1N1, H3N2).
  • RIDTs: Antigen detection. Quick, lower sensitivity.
  • Viral Culture: Slow. For resistance testing.
  • Serology: Paired sera for Ab rise (HI test). Retrospective.
• Management:
  • Supportive care: Rest, fluids, antipyretics.
  • Antivirals (best if <48h onset):
    • NAIs: Oseltamivir (oral), Zanamivir (inhaled), Peramivir (IV). Inhibit viral release. Active: Flu A & B.
    • M2 Blockers (Adamantanes): Amantadine. ⚠️ High resistance; NOT recommended.
• Prevention:
  • Annual Vaccination: Key strategy.
    • IIV: IM/ID. Trivalent (2A,1B) or Quadrivalent (2A,2B).
    • LAIV: Intranasal.
  • Hand hygiene, respiratory etiquette.

⭐ Antivirals (e.g., Oseltamivir) most effective if started <48h of symptoms; reduce duration/severity.

High‑Yield Points - ⚡ Biggest Takeaways

• Orthomyxoviruses (Influenza) feature a segmented RNA genome (8 segments A/B), enabling antigenic shift (pandemics).
• Antigenic drift (mutations) causes seasonal epidemics.
• Key glycoproteins: HA (entry), NA (release); both drug targets.
• Replication is unique for RNA viruses: occurs in the host cell nucleus.
• Aspirin use during infection risks Reye's syndrome in children.
• Oseltamivir/Zanamivir (NA inhibitors) treat Influenza A & B.
• Amantadine (M2 inhibitor) for Influenza A; resistance common.