Step 1 · Microbiology

Influenza & Paramyxoviruses

Name: Influenza & Paramyxoviruses
Creator: Veli Bakalov, MD

Negative-strand RNA viruses that ride the respiratory tract

Microbiology·Virology·6 min read·8 high-yield points·Reviewed by Veli Bakalov, MD @HemeOncBuddy

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Influenza is an enveloped orthomyxovirus with 8 segments of negative-sense RNA that replicates in the nucleus; hemagglutinin binds sialic acid for entry and neuraminidase cleaves it to release virions (blocked by oseltamivir and zanamivir).
Antigenic drift (point mutations in HA/NA) causes seasonal epidemics and yearly vaccine updates; antigenic shift (segment reassortment, influenza A only, often in pigs) causes pandemics.
Post-influenza bacterial pneumonia (S. pneumoniae, S. aureus including necrotizing MRSA, H. influenzae) classically follows initial improvement; aspirin in children risks Reye syndrome.
Inactivated or recombinant injectable flu vaccines are safe in pregnancy and immunocompromise; the live attenuated intranasal vaccine is limited to healthy nonpregnant people aged 2–49.
Paramyxoviruses (parainfluenza, measles, mumps) and pneumoviruses (RSV, metapneumovirus) are nonsegmented negative-sense RNA viruses whose F protein fuses cells into syncytia.
Parainfluenza causes croup (barking cough, inspiratory stridor, steeple sign), treated with dexamethasone; RSV is the top cause of infant bronchiolitis, prevented by the anti-F antibody nirsevimab or maternal RSV vaccination at 32–36 weeks.
Measles: fever with cough, coryza, conjunctivitis, then Koplik spots, then a rash spreading from the hairline downward; Warthin-Finkeldey giant cells; pneumonia, encephalitis, SSPE years later, and immune amnesia; vitamin A lowers mortality.
Mumps causes parotitis, orchitis, oophoritis, aseptic meningitis, and pancreatitis; MMR is live attenuated, given at 12–15 months and 4–6 years, and contraindicated in pregnancy and severe immunodeficiency.

Influenza virus: structure and life cycle

Structure. Influenza (family Orthomyxoviridae) is an enveloped virus whose genome is 8 separate segments of negative-sense single-stranded RNA, each packaged with its own RNA-dependent RNA polymerase. Unusually for an RNA virus it transcribes and replicates in the nucleus, where its polymerase "cap-snatches" 5′ caps from host pre-mRNAs. Type A infects birds, pigs, and humans and is subtyped by its hemagglutinin (HA) and neuraminidase (NA), such as H1N1 and H3N2; type B is essentially human-only.

HA binds sialic acidOn respiratory epithelium; anti-HA antibodies neutralize and are the main vaccine target
Endocytosis and low-pH fusionThe M2 ion channel acidifies the virion and the genome travels to the nucleus
Nuclear transcription and replicationNew segments are assembled at the plasma membrane
NA cleaves sialic acidFrees progeny virions from the cell and helps them cross mucus

Influenza entry and exit

Drug targets. Oseltamivir, zanamivir, and peramivir inhibit neuraminidase, trapping new virions on the cell surface; baloxavir blocks the cap-dependent endonuclease; the old M2 blockers (amantadine) are no longer used because of resistance. Pharmacology details are in the antivirals lesson.

Antigenic variation and clinical disease

Drift and shift. Influenza's surface antigens change in two ways, compared below. Human-adapted strains bind α2,6-linked sialic acid of the upper airway, whereas avian strains prefer α2,3 linkages; pigs carry both, which makes them ideal "mixing vessels" for reassortment.

Antigenic drift vs antigenic shift

Feature	Drift	Shift
Mechanism	Point mutations in HA and NA genes by the error-prone polymerase	Reassortment of whole segments when two strains (e.g., human and avian) coinfect a cell
Types	A and B	A only
Antigenic change	Minor; partial immunity persists	New HA or NA subtype; no population immunity
Result	Seasonal epidemics; annual vaccine update	Pandemics (1918 H1N1; 2009 H1N1 with swine, avian, and human segments)

Presentation and diagnosis. Spread by droplets in winter epidemics, influenza starts abruptly after a 1–4 day incubation: high fever, chills, myalgias, headache, sore throat, and dry cough. A rapid molecular (RT-PCR) nasopharyngeal test confirms it. Neuraminidase inhibitors help most within 48 hours of onset but are given at any time to hospitalized or high-risk patients (age ≥65, young children, pregnancy, chronic heart or lung disease, immunosuppression, nursing-home residents).

Complications. Influenza strips the ciliated epithelium, so secondary bacterial pneumonia — S. pneumoniae, S. aureus (including necrotizing, cavitating MRSA), and H. influenzae — classically appears as fever returns after initial improvement. Others include primary viral pneumonia, myositis with calf pain and high CK (especially children with influenza B), and myocarditis.

Aspirin during influenza or varicella can cause Reye syndrome — mitochondrial injury with microvesicular fatty liver and encephalopathy — so aspirin is avoided in children.

Influenza vaccines (annual, everyone ≥6 months)

Feature	Inactivated or recombinant HA (injected)	Live attenuated (intranasal)
Content	Killed virus or recombinant HA protein	Cold-adapted virus that replicates only in cool nasal passages
Ages	≥6 months	2–49 years, healthy and nonpregnant
Pregnancy, immunocompromise	Safe and recommended	Avoid
Other exclusions	—	Young children with asthma or wheezing; children taking aspirin

Egg allergy is no longer a reason to withhold any influenza vaccine.

Paramyxoviruses and pneumoviruses

Family features. Parainfluenza, measles, and mumps are paramyxoviruses: enveloped, nonsegmented negative-sense RNA viruses that replicate in the cytoplasm. Attachment proteins differ — hemagglutinin-neuraminidase (parainfluenza, mumps), H (measles), G (RSV) — but all use an F (fusion) protein that merges the envelope with the plasma membrane and fuses neighboring cells into multinucleated syncytia. RSV and human metapneumovirus are now classed as Pneumoviridae but share the F-protein strategy.

Croup. Parainfluenza (mainly type 1) causes laryngotracheobronchitis in children 6 months to 3 years, often in fall: low-grade fever, barking cough, hoarseness, and inspiratory stridor. Subglottic swelling tapers the trachea into a "steeple sign" on an AP neck film. One dose of dexamethasone is standard, with nebulized racemic epinephrine for stridor at rest. Epiglottitis (Hib) instead causes drooling and toxicity with a "thumb sign."

RSV. The leading cause of bronchiolitis and pneumonia in infants under 1 year, peaking in winter: rhinorrhea, then cough, wheezing, crackles, tachypnea, and retractions, with apnea in young or premature infants. Treatment is supportive — oxygen, suctioning, hydration — without routine bronchodilators or steroids. RSV also causes serious disease in older adults, and human metapneumovirus produces an identical bronchiolitis, often in slightly older children.

RSV prevention. Nirsevimab, a single-dose, long-acting monoclonal antibody against the F protein, protects infants entering their first RSV season; palivizumab, a monthly anti-F antibody, is the older option. Alternatively, a prefusion F vaccine given to the mother at 32–36 weeks' gestation during RSV season sends protective IgG across the placenta.

Measles and mumps

Measles. One of the most contagious airborne infections; patients shed virus from 4 days before to 4 days after rash onset. The virus enters immune cells through CD150 (SLAM) and epithelium through nectin-4.

ProdromeHigh fever with cough, coryza, and conjunctivitis
Koplik spotsTiny blue-white spots on red buccal mucosa opposite the molars, 1–2 days before the rash; pathognomonic
RashMaculopapular, starting at the hairline and spreading down the trunk and limbs, becoming confluent
ResolutionFades in the same order, leaving brownish staining and fine peeling

Classic course of measles

Pathology and complications. Measles fuses lymphoid cells into Warthin-Finkeldey giant cells in tonsils, lymph nodes, and appendix. Otitis media and diarrhea are common. Pneumonia — viral or secondary bacterial — is the leading cause of measles death; in patients with severe T-cell deficiency, giant-cell pneumonia can occur without any rash, because the rash is T-cell mediated. Acute encephalitis strikes about 1 in 1,000 cases. Subacute sclerosing panencephalitis appears 7–10 years later from persistent defective virus, with cognitive decline, myoclonus, very high CSF measles antibody, and death. Measles also causes "immune amnesia," destroying memory lymphocytes and erasing prior immunity. There is no specific antiviral, but vitamin A lowers complications and mortality.

Mumps. Spread by respiratory droplets, mumps causes painful parotitis, often bilateral, with a raised serum amylase. Complications include orchitis in postpubertal males (usually unilateral; testicular atrophy, rarely sterility), oophoritis, aseptic meningitis, pancreatitis, and sensorineural hearing loss. Outbreaks still occur on college campuses as vaccine immunity wanes.

MMR vaccine. A live attenuated vaccine given at 12–15 months and 4–6 years. It is contraindicated in pregnancy (avoid conception for 4 weeks afterward) and severe immunodeficiency, but given in HIV when the CD4 count is ≥200. After measles exposure, MMR within 72 hours or immune globulin within 6 days can prevent disease. Egg allergy is not a contraindication; the measles and mumps components are grown in chick embryo fibroblast culture.