ORTHOMYXOVIRUS – INFLUENZA VIRUS

Q. What is Orthomyxovirus

– Influenza virus?

• Orthomyxoviridae family, enveloped RNA virus causing seasonal flu in humans and animals.

Q. What are the types of Influenza virus relevant for humans?

• Influenza A (most pathogenic, many subtypes) → H & N numbers (e.g., H1N1, H3N2)
• Influenza B (only one lineage, less severe)
• Influenza C (mild respiratory illness, rare)

Q. What is the morphology of Influenza virus?

• Spherical or slightly pleomorphic, 80‑120 nm diameter.
• Lipid bilayer envelope studded with glycoprotein spikes.
• Two major surface antigens: Hemagglutinin (H) – binds sialic acid, and Neuraminidase (N) – releases progeny.
• Matrix protein (M1) underneath envelope gives shape.
• Inside, eight single‑stranded negative‑sense RNA segments each bound to nucleoprotein (NP) and polymerase complex (PA, PB1, PB2).

Q. How does the virus cause disease? (Pathogenesis – stepwise)

1. Inhalation of aerosol droplets → virus reaches nasal‑pharyngeal epithelium.
2. HA binds sialic acid receptors on respiratory epithelial cells → attachment.
3. Virus is endocytosed; low pH in endosome triggers HA conformational change → fusion of viral envelope with endosomal membrane.
4. Viral ribonucleoprotein (vRNP) released into cytoplasm → transported to nucleus.
5. Viral RNA transcription & replication in nucleus using viral RNA‑dependent RNA polymerase.
6. New viral proteins synthesized in cytoplasm, vRNPs re‑imported to nucleus for assembly.
7. Budding at plasma membrane where HA, NA, M2 gather; M1 lines interior, NP‑RNA packaged.
8. NA cleaves sialic acid → release of mature virions → spread to adjacent cells and lower respiratory tract.

Memory trick for steps 1‑8: “I H E F V A B N” → Inhaled, HA binds, Endocytosis, Fusion, VRNA made, Assembly, Budding, Neuraminidase release.

Q. What are the clinical features of Influenza infection?

• Sudden high fever (≥38.5 °C) → chills, rigors.
• Headache, myalgia, arthralgia (“flu‑like aches”).
• Dry cough, sore throat, nasal congestion or rhinorrhea.
• Generalized fatigue, loss of appetite.
• In children: vomiting, diarrhea may appear.

Q. What complications can arise?

• Primary viral pneumonia → severe respiratory distress.
• Secondary bacterial pneumonia (Streptococcus pneumoniae, Staph aureus).
• Otitis media, sinusitis.
• Exacerbation of asthma, COPD, cardiac failure.
• Rare: encephalitis, myocarditis, Reye’s syndrome in children on aspirin.

Q. How is Influenza diagnosed in the lab?

• Rapid influenza diagnostic test (RIDT) – immunochromatographic detection of NP antigen (gives result in 15 min).
• Real‑time RT‑PCR – gold standard, detects HA/NA gene segments, high sensitivity.
• Viral culture in MDCK cells – confirms live virus, used for antiviral susceptibility.
• Serology (Hemagglutination Inhibition, Microneutralization) – four‑fold rise in antibody titer in convalescent serum (useful for epidemiology).

Q. How is Influenza prevented and managed?

• Annual inactivated trivalent/quadrivalent vaccine (covers prevailing H & N strains).
• Good respiratory hygiene: hand washing, covering mouth/nose, avoiding close contact.
• Antiviral therapy within 48 h of symptom onset:
  • Oseltamivir (oral) – neuraminidase inhibitor.
  • Zanamivir (inhaled) – neuraminidase inhibitor.
  • Baloxavir (single dose, cap‑dependent endonuclease inhibitor).
• Supportive care: antipyretics, adequate hydration, rest.

Q. Quick recall rhyme for the three human‑relevant types: “A‑B‑C, flu’s ABC”.

(Points are concise, exam‑oriented, and follow NCH/MUHS format.)1. Orthomyxovirus = family of enveloped, negative‑sense, single‑stranded RNA viruses; segmented genome (7‑8 segments).
2. Influenza virus = member of Orthomyxoviridae that causes acute respiratory infection in humans and animals.

3. Causes / transmission

   • Respiratory droplets, aerosols, fomites.
   • Human‑to‑human spread most common; birds (especially waterfowl) are natural reservoir for type A; pigs act as mixing vessels.

4. Types of influenza virus

   • Type A → subtyped by surface glycoproteins HA (H1‑H18) and NA (N1‑N11); infects humans, birds, pigs; causes pandemics.
   • Type B → two lineages (Yamagata, Victoria); only humans; milder epidemics.
   • Type C → causes mild respiratory illness; humans & pigs.
   • Type D → identified in cattle, not a human pathogen (mentioned in recent texts).

5. Antigenic variation (Robbins)

   • Antigenic drift = point mutations in HA/NA → seasonal epidemics.
   • Antigenic shift = reassortment of gene segments (especially in type A) → pandemic strains.

6. Morphology & structure

   • Spherical/pleomorphic virion, 80‑120 nm diameter.
   • Lipid envelope derived from host cell membrane.
   • Surface spikes: Hemagglutinin (HA) – binds sialic acid receptors; Neuraminidase (NA) – cleaves sialic acid to release virions; M2 ion channel.
   • Inside: 8 RNA segments each bound to nucleoprotein (NP) and polymerase complex (PA, PB1, PB2).

7. Life‑cycle (step‑wise, arrows)

   1. → HA binds α‑2,6‑sialic acid on nasal‑pharyngeal epithelial cells.
   2. → Virus is endocytosed into clathrin‑coated vesicle.
   3. → Low pH in endosome triggers M2 ion channel → influx of H⁺, uncoating of ribonucleoprotein (RNP).
   4. → Viral RNA (vRNA) transported to nucleus; transcription → mRNA (capped, poly‑A) using host‑derived cap‑snatching.
   5. → Translation of viral proteins in cytoplasm; replication of vRNA (cRNA intermediate).
   6. → Assembly of new RNPs at cell membrane; HA, NA, M2 inserted into budding site.
   7. → Budding of virion; NA cleaves sialic acid → release of mature virion.

8. Pathogenesis (step‑wise)

   1. → Virus infects nasal and bronchial epithelium.
   2. → HA‑mediated entry → cell death (necrosis) and loss of cilia.
   3. → Release of pro‑inflammatory cytokines (IL‑1, IL‑6, TNF‑α) → fever, malaise.
   4. → Increased vascular permeability → alveolar exudate, edema.
   5. → Secondary bacterial colonisation possible due to damaged epithelium.

9. Clinical features (Harsh Mohan, Chatterjee)

   • Incubation 1‑4 days.
   • Sudden high fever, chills, severe myalgia, headache, dry cough, sore throat, nasal congestion.
   • Often “flu‑like” with rapid onset and short course (5‑7 days).
   • High‑risk groups: children <5 yr, elderly >65 yr, pregnancy, chronic lung/heart disease, immunocompromised.

10. Complications (Robbins, NCH)

    • Primary viral pneumonia (diffuse alveolar damage).
    • Secondary bacterial pneumonia (Streptococcus pneumoniae, Staph aureus).
    • Otitis media, sinusitis.
    • Encephalitis, myocarditis, myositis.
    • Reye’s syndrome in children given aspirin.

11. Diagnosis (Ananthanarayan & Paniker)

    • Clinical suspicion during epidemic season.
    • Rapid Influenza Diagnostic Test (RIDT) – antigen detection (10‑30 min).
    • Direct immunofluorescence of nasopharyngeal swab.
    • RT‑PCR – gold standard, detects HA/NA subtypes.
    • Viral culture in MDCK cells (research/epidemiology).
    • Paired serology (four‑fold rise in HI antibody).

12. Management (Harsh Mohan, NCH)

    • Supportive: bed rest, adequate fluids, antipyretics (paracetamol/ibuprofen).
    • Antivirals (within 48 h of onset):
      • Neuraminidase inhibitors – oseltamivir, zanamivir, peramivir (effective against A & B).
      • Adamantanes (amantadine, rimantadine) – only type A, high resistance, rarely used.
    • Indications for antivirals: high‑risk patients, severe disease, hospitalized cases.
    • Antibiotics only for proven/suspected secondary bacterial infection.

13. Prevention (NCH, MUHS)

    • Annual influenza vaccination (trivalent or quadrivalent) – includes predicted HA/NA strains.
    • Vaccine types: inactivated (IIV), live‑attenuated intranasal (LAIV), recombinant HA.
    • Hand hygiene, respiratory etiquette, mask use during outbreaks.
    • Isolation of infected individuals for ≥5 days after symptom onset.

14. Important exam points from textbooks

    • HA mediates attachment → “H = Hook”.
    • NA mediates release → “N = Nix”.
    • Antigenic drift = “small change = seasonal”.
    • Antigenic shift = “big swap = pandemic”.
    • Type A can undergo reassortment because of 8‑segment genome.
    • M2 ion channel is target of adamantanes.
    • Neuraminidase inhibitors block virion release → reduce symptom duration by ~1 day.

15. Memory trick for life‑cycle (A V I R U S)
    A – Attach (HA binds) →
    V – Vesicle (endocytosis) →
    I – Ion channel opens (M2) →
    R – Replicate (nuclear transcription) →
    U – Assemble (RNP + HA/NA at membrane) →
    S – Shed (NA cleaves, virion released).

16. Memory rhyme for HA/NA functions
    “HA grabs the door, NA opens the floor – hook‑and‑release, flu’s encore.”

(All points are in simple, handwritten‑style language, point‑wise, with arrows where flow is shown, covering definition, causes, types, morphology, pathogenesis, life‑cycle, clinical picture, complications, diagnosis, management, prevention, and key exam‑focused facts from Robbins, Harsh Mohan, Ananthanarayan & Paniker, Chatterjee, and NCH.)