RNA Respiratory Viruses

Respiratory viruses cause the bulk of acute upper and lower respiratory infections worldwide. For NEET PG, the high-yield cluster is Influenza (Orthomyxovirus), RSV and Parainfluenza (Paramyxoviruses), Rhinovirus (Picornavirus) and the lone DNA exception, Adenovirus. This note is structured around the receptors, antigenic mechanisms, syndromes and named therapeutics that examiners repeatedly test.

Classification & overview

The medically important respiratory viruses span several families. Note that Adenovirus is a DNA virus — it is included here because it produces classic respiratory syndromes and is frequently grouped with the rest in MCQs as a "trap."

Virus	Family	Genome	Envelope	Key receptor
Influenza A/B/C	Orthomyxoviridae	ssRNA, −ve sense, segmented (8)	Enveloped	Sialic acid (HA binds)
Respiratory syncytial virus (RSV)	Pneumoviridae (formerly Paramyxoviridae)	ssRNA, −ve sense, non-segmented	Enveloped	Surface G/F glycoproteins
Parainfluenza	Paramyxoviridae	ssRNA, −ve sense, non-segmented	Enveloped	Sialic acid
Rhinovirus	Picornaviridae	ssRNA, +ve sense	Non-enveloped	ICAM-1 (major group)
Adenovirus	Adenoviridae	dsDNA	Non-enveloped	CAR (coxsackie-adenovirus receptor)

High-yield: Influenza is the ONLY respiratory virus with a segmented genome — this single fact underlies antigenic shift, reassortment and pandemics. Remember the segmented RNA viruses by BOAR: Bunya, Orthomyxo, Arena, Reo.

High-yield: Rhinovirus and Adenovirus are non-enveloped → resistant to ether/detergents and survive on fomites, explaining hand/surface transmission. Enveloped respiratory viruses (Influenza, RSV, Parainfluenza) are labile.

Influenza virus

Structure & antigens

• Orthomyxovirus, helical nucleocapsid, enveloped, 8 segments of −ve sense ssRNA.
• Carries its own RNA-dependent RNA polymerase (all −ve sense RNA viruses do).
• Surface spikes:
  • Haemagglutinin (HA) — binds sialic acid receptor, mediates attachment & fusion; the major neutralising antigen; agglutinates RBCs. ~18 subtypes (H1–H18).
  • Neuraminidase (NA) — cleaves sialic acid, releases progeny virions from infected cells, prevents clumping. ~11 subtypes (N1–N11). Target of oseltamivir/zanamivir.
• Internal proteins: M (matrix) and NP (nucleoprotein) are type-specific and used to classify A vs B vs C.

High-yield: HA mediates adsorption + haemagglutination; NA mediates release/budding. NA inhibitors block release; M2 inhibitors (amantadine) block uncoating — Influenza A only.

Antigenic drift vs antigenic shift

Feature	Antigenic drift	Antigenic shift
Mechanism	Point mutations in HA/NA genes	Reassortment of whole segments
Magnitude	Minor, gradual	Major, abrupt — new subtype
Genome event	Accumulated mutations	Genetic exchange between two strains in one cell
Result	Seasonal epidemics	Pandemics
Occurs in	Influenza A and B	Influenza A only
Reason	Lack of proofreading by RNA polymerase	Segmented genome allows mixing

Flow of a pandemic strain → Two influenza A strains (e.g. human + avian) co-infect one host cell (classically the pig = "mixing vessel") → 8 segments from each repackage randomly → reassortant virus with a novel HA → no pre-existing population immunity → pandemic.

High-yield: Antigenic shift = reassortment = pandemic = Influenza A only. Drift occurs in both A and B and necessitates annual vaccine reformulation. This drift–shift contrast is one of the most repeated micro MCQs.

• Pandemic examples: 1918 H1N1 (Spanish flu), 1957 H2N2 (Asian), 1968 H3N2 (Hong Kong), 2009 H1N1 (swine flu, pdm09). Avian H5N1/H7N9 cause severe zoonotic disease but limited human-to-human spread.

Clinical features

• Incubation 1–4 days; abrupt fever, myalgia, headache, dry cough, prostration ("hits like a truck" — more systemic than common cold).
• Complications: primary viral pneumonia, secondary bacterial pneumonia (classically Staph. aureus, also Strep. pneumoniae, H. influenzae), myositis, myocarditis, Reye syndrome (aspirin in children), and Guillain–Barré syndrome (post-vaccination/infection association).

High-yield: The deadliest acute complication is secondary Staphylococcus aureus pneumonia following influenza. Never give aspirin to febrile children with influenza/varicella → Reye syndrome.

Diagnosis

• RT-PCR is the investigation of choice (most sensitive/specific).
• Rapid antigen tests (RIDT) detect NP — fast but lower sensitivity.
• Viral culture in embryonated egg amniotic/allantoic cavity or MDCK cells; detected by haemadsorption / haemagglutination inhibition (HAI) — HAI titre is the classic serological/strain-typing tool.

Management & prevention

• Neuraminidase inhibitors — oseltamivir (oral, drug of choice), zanamivir (inhaled), peramivir (IV). Effective against A and B; most benefit if started within 48 hours.
• Baloxavir marboxil — cap-dependent endonuclease (polymerase) inhibitor, single dose.
• M2 ion-channel blockers — amantadine/rimantadine: Influenza A only, widespread resistance → no longer recommended.
• Vaccines: inactivated (IM, killed) and live attenuated (LAIV, intranasal). Reformulated yearly based on circulating strains. LAIV contraindicated in pregnancy, immunocompromised, young children with wheeze.

Respiratory syncytial virus (RSV)

• Paramyxovirus-like (now Pneumoviridae); enveloped, non-segmented −ve ssRNA. No HA, no NA — surface proteins are G (attachment) and F (fusion).
• The F protein causes cell-to-cell fusion → multinucleated giant cells (syncytia), the cytopathic hallmark and source of the name.

Clinical

• Most common cause of bronchiolitis and pneumonia in infants <2 years, and the commonest cause of LRTI hospitalisation in infants worldwide.
• Bronchiolitis: wheeze, tachypnoea, chest retractions, hyperinflation, apnoea in young infants.
• Lacks lasting immunity → reinfections throughout life; mild "cold" in adults but severe in elderly/immunocompromised.

Diagnosis & management

• Rapid antigen detection / RT-PCR of nasopharyngeal aspirate; syncytia in culture.
• Treatment is largely supportive (oxygen, hydration). Ribavirin reserved for severe immunocompromised cases.
• Prevention — high-yield therapeutics:
  • Palivizumab — humanised monoclonal antibody against the F protein; passive prophylaxis in high-risk infants (prematurity, chronic lung disease, congenital heart disease).
  • Nirsevimab — long-acting anti-F monoclonal (newer, single-dose for the season).
  • Maternal RSVpreF vaccine and an adult (≥60 y) vaccine are now available.

High-yield: Palivizumab = anti-F monoclonal, given for PREVENTION (not treatment) of RSV in high-risk infants. RSV's F protein → syncytia. There is no live RSV vaccine for infants because of the historical enhanced disease seen with the formalin-inactivated vaccine.

Parainfluenza virus

• Paramyxovirus; enveloped, non-segmented −ve ssRNA; has both HA and NA (unlike RSV) plus an F protein → also forms syncytia.
• Types 1–4. Type 1 (and 2) are the leading cause of croup (acute laryngotracheobronchitis) in children 6 months–3 years; type 3 causes bronchiolitis/pneumonia (second to RSV).

Croup

• Barking/seal-like cough, inspiratory stridor, hoarseness, low-grade fever, worse at night.
• Steeple sign (subglottic narrowing) on AP neck radiograph.
• Management: humidified air, nebulised adrenaline for stridor at rest, and dexamethasone (single dose) as the mainstay.

High-yield: Parainfluenza → croup → steeple sign. Contrast with epiglottitis (H. influenzae b → thumb sign, drooling, tripod posture) — a favourite distractor pair.

Feature	Croup (parainfluenza)	Acute epiglottitis (Hib)
Onset	Gradual, after URI	Sudden, toxic
Cough	Barking/seal-like	Usually absent
Stridor	Inspiratory	Soft, muffled
Voice	Hoarse	Muffled ("hot potato")
Drooling	No	Yes
X-ray sign	Steeple sign	Thumb sign
Site	Subglottic	Supraglottic

Rhinovirus

• Picornavirus, +ve sense ssRNA, non-enveloped, icosahedral; >100 serotypes (explains why immunity does not prevent recurrent colds).
• Major group binds ICAM-1 (CD54); minor group binds LDL receptor.
• Acid-labile (destroyed at gastric pH, unlike enteroviruses) and grows best at 33 °C — the temperature of the nasal passages, explaining its restriction to the upper airway.
• Most common cause of the common cold (coryza): sneezing, rhinorrhoea, sore throat, low-grade or no fever; self-limiting. Can trigger asthma/COPD exacerbations.

High-yield: Rhinovirus receptor = ICAM-1; optimal growth at 33 °C; acid-labile (distinguishes it from other enteroviruses which are acid-stable). >100 serotypes → no effective vaccine. Treatment is symptomatic.

Adenovirus (the DNA exception)

• dsDNA, non-enveloped, icosahedral with penton fibres (antigen used for attachment/haemagglutination).
• Syndromes are exam gold:
  • Pharyngoconjunctival fever — fever + pharyngitis + conjunctivitis; outbreaks linked to swimming pools (types 3, 7).
  • Epidemic keratoconjunctivitis ("shipyard eye"; type 8, 19, 37).
  • Acute respiratory disease (ARD) in military recruits (types 4, 7).
  • Acute haemorrhagic cystitis (types 11, 21) and gastroenteritis in children (types 40, 41 — non-cultivable "fastidious" enteric adenoviruses).
• Forms intranuclear basophilic inclusions ("smudge cells"); latency in adenoids/tonsils.

High-yield: Pharyngoconjunctival fever + swimming pool = Adenovirus. Smudge cells = adenovirus inclusions. Enteric adenovirus types 40 & 41 cause childhood diarrhoea and need special HEK cell lines to grow.

Differentiating the syndromes

Stepwise clinical approach → identify the dominant syndrome → match to virus:

1. Pure runny nose, no/low fever, adult → Rhinovirus (or coronavirus).
2. Abrupt high fever + myalgia + dry cough, winter epidemic → Influenza.
3. Wheezing infant <2 y, bronchiolitis → RSV.
4. Barking cough + stridor + steeple sign, toddler → Parainfluenza (croup).
5. Sore throat + red eyes + fever, pool outbreak → Adenovirus.

Virus	Signature syndrome	Diagnostic/receptor clue	Key drug/prophylaxis
Influenza	Epidemic febrile flu	Segmented genome; HA/NA; HAI	Oseltamivir; annual vaccine
RSV	Infant bronchiolitis	Syncytia (F protein)	Palivizumab/nirsevimab
Parainfluenza	Croup	Steeple sign	Dexamethasone + nebulised adrenaline
Rhinovirus	Common cold	ICAM-1, 33 °C, acid-labile	Symptomatic only
Adenovirus	Pharyngoconjunctival fever	Smudge cells, swimming pool	Supportive; oral vaccine (military)

Key differentials & traps

• RSV vs Parainfluenza: RSV has G + F only (no HA/NA); parainfluenza has HA + NA + F. Both cause syncytia; RSV → bronchiolitis, parainfluenza → croup.
• Influenza vs common cold: influenza is abrupt and systemic; the cold is gradual and localised to the nose/throat.
• Croup vs epiglottitis: steeple vs thumb sign (table above).
• Measles/Mumps are also Paramyxoviruses but are systemic exanthems/parotitis, not primarily respiratory — don't confuse the family with the syndrome.
• Coronaviruses (incl. SARS-CoV-2) are +ve sense, enveloped RNA viruses causing colds to severe pneumonia — a modern differential for influenza-like illness.

Recently asked / exam angle

• "Which respiratory virus has a segmented genome?" → Influenza.
• "Antigenic shift occurs in which type and by what mechanism?" → Influenza A, by reassortment → pandemics.
• "Receptor for major-group rhinovirus?" → ICAM-1.
• "Monoclonal antibody for RSV prophylaxis in preterm infants?" → Palivizumab (anti-F).
• "Cause of syncytia in respiratory epithelium?" → RSV (F protein) / Parainfluenza.
• "Steeple sign vs thumb sign" pairing → Parainfluenza croup vs Hib epiglottitis.
• "Swimming-pool conjunctivitis + fever" → Adenovirus (pharyngoconjunctival fever).
• "Drug of choice for influenza A & B" → Oseltamivir (NA inhibitor); amantadine no longer used (resistance, A only).
• "Why annual influenza vaccine?" → antigenic drift.
• "Why is rhinovirus restricted to the upper airway?" → optimal replication at 33 °C and acid lability.

Rapid revision

1. Influenza = only segmented respiratory virus → reassortment → pandemics (mnemonic BOAR for segmented RNA viruses).
2. HA = attachment + haemagglutination; NA = release/budding (target of oseltamivir).
3. Drift = point mutation = epidemic (A & B); Shift = reassortment = pandemic (A only); pig = mixing vessel.
4. Worst acute influenza complication = secondary Staph. aureus pneumonia; avoid aspirin (Reye syndrome).
5. Influenza Ix of choice = RT-PCR; classic typing tool = haemagglutination inhibition (HAI); cultured in embryonated egg.
6. RSV = commonest cause of infant bronchiolitis; F protein → syncytia; no HA/NA; prevented by palivizumab/nirsevimab.
7. Parainfluenza = commonest cause of croup → steeple sign; treat with dexamethasone + nebulised adrenaline.
8. Epiglottitis (Hib) = thumb sign, drooling, tripod — distinguish from croup.
9. Rhinovirus = commonest common cold; receptor ICAM-1; grows at 33 °C; acid-labile; >100 serotypes → no vaccine.
10. Adenovirus = the DNA odd-one-out; pharyngoconjunctival fever (swimming pool), smudge cells, enteric types 40/41 cause childhood diarrhoea.
11. Non-enveloped respiratory viruses = Rhinovirus + Adenovirus → survive on fomites, ether-resistant.
12. Live attenuated influenza vaccine (LAIV, intranasal) is contraindicated in pregnancy and the immunocompromised.