Negative Sense RNA Viruses: Orthomyxoviruses and Paramyxoviruses

These viruses carry negative-sense, single-stranded RNA genomes and therefore require a virion-packaged RNA-dependent RNA polymerase for initial transcription into mRNA. All are enveloped, and all replicate predominantly in the cytoplasm, with influenza's nuclear replication as the specific exception within this group.

Orthomyxoviruses are enveloped, negative-sense, single-stranded, segmented RNA viruses, eight segments for influenza A and B. This segmentation directly enables reassortment and is the single most clinically important structural feature of this family.

Influenza A, B, and C. Influenza A is the only type capable of infecting a broad range of non-human hosts, birds, pigs, and other mammals, in addition to humans. This reservoir diversity directly underlies its capacity for genetic shift via reassortment and, consequently, its status as the only influenza type with recognised pandemic potential.

Influenza B infects predominantly humans, with a limited seal reservoir recognised. It causes seasonal disease generally similar in clinical severity to influenza A, but without the pandemic potential of influenza A. Its host range is much more restricted, giving correspondingly limited opportunity for the kind of cross-species reassortment that produces genetic shift.

Influenza C causes generally mild, often subclinical respiratory illness, of comparatively minor overall clinical and epidemiological significance relative to types A and B.

Haemagglutinin is the major surface glycoprotein, mediating attachment to host cell sialic-acid-containing receptors and subsequent membrane fusion following endosomal acidification. It is the principal target of neutralising antibody and, correspondingly, the primary antigen driving both seasonal vaccine formulation and the strain-naming convention, the "H" in designations such as H1N1 and H3N2.

Neuraminidase is the second major surface glycoprotein, an enzyme that cleaves sialic acid residues, a function required for newly assembled virions to be released efficiently from the surface of an infected cell.

Without neuraminidase activity, progeny virions would remain aggregated at the infected cell surface via ongoing haemagglutinin-sialic acid binding, unable to disseminate to infect further cells.

Neuraminidase is the "N" in strain designations and the specific molecular target of the neuraminidase inhibitor class of antiviral drugs, oseltamivir and related agents.

Antigenic drift is the gradual accumulation of point mutations in haemagglutinin and neuraminidase, the mechanism necessitating annual reformulation of the seasonal influenza vaccine, producing the recurring seasonal epidemic pattern.

Antigenic shift is abrupt genetic reassortment, requiring a segmented genome, producing a novel haemagglutinin and neuraminidase combination against which the population has little or no pre-existing immunity, the mechanism underlying influenza's recognised pandemic potential and historically responsible for each of the major influenza pandemics.

Disease presents as acute febrile respiratory illness: fever, myalgia, headache, cough, sore throat, generally more systemically severe in its symptom profile than the typical common cold caused by rhinovirus. Complications include secondary bacterial pneumonia, classically Streptococcus pneumoniae or Staphylococcus aureus, superinfecting influenza-damaged respiratory epithelium, primary viral pneumonia, and, in children, a recognised association with encephalopathy and myositis in some cases.

Diagnosis relies on PCR from a respiratory specimen, the standard, most sensitive approach, and rapid antigen testing, faster but lower sensitivity, useful for point-of-care triage.

Paramyxoviruses are enveloped, negative-sense, single-stranded RNA viruses, characteristically nonsegmented in contrast to the orthomyxoviruses, with helical nucleocapsid symmetry. As a family, they have a well-recognised propensity for causing syncytium formation, multinucleated giant cell formation via cell-to-cell fusion. This is a shared histopathological and immune-evasion-relevant feature across several members of this family.

Measles virus

Transmission is by respiratory droplets and airborne spread. Measles is among the most contagious viruses known, with a basic reproduction number substantially higher than most other respiratory viruses. Tropism is respiratory epithelium initially, with the classic primary and secondary viraemia dissemination pattern delivering virus to skin, and, in a small proportion of cases, the central nervous system.

Disease begins with a prodromal phase, fever, cough, coryza, conjunctivitis, and the pathognomonic Koplik spots, small white lesions on the buccal mucosa appearing shortly before the rash itself. A characteristic cephalocaudal spreading maculopapular rash follows, beginning on the face and hairline and spreading downward over several days.

Complications include otitis media, pneumonia, the leading cause of measles-related mortality, acute encephalitis, and, rarely, subacute sclerosing panencephalitis, a delayed, typically seven to ten years post-infection, progressive, fatal neurodegenerative complication reflecting persistent, aberrant measles virus infection of the central nervous system.

Diagnosis is predominantly clinical given the highly characteristic prodrome, Koplik spots, and rash sequence in an appropriate epidemiological context. Serology, IgM, and PCR confirm the diagnosis, particularly important for public health notification and outbreak response given measles's high transmissibility and vaccine-preventable status.

Mumps virus

Transmission is by respiratory droplets. Tropism is respiratory epithelium initially, with subsequent viraemic spread to the salivary glands, classically the parotid, and, in a proportion of cases, other glandular and neural tissue.

Parotitis, painful, often bilateral parotid gland swelling, is the classic presentation. Recognised complications include orchitis, testicular inflammation, generally unilateral, occurring predominantly in postpubertal males, with a small associated risk of subfertility, though bilateral involvement and complete infertility are both uncommon, oophoritis, pancreatitis, and aseptic meningitis or encephalitis.

Diagnosis is predominantly clinical given the characteristic parotid swelling, with PCR or serology, IgM, for confirmation where needed, particularly relevant for outbreak investigation in partially vaccinated populations.

Parainfluenza viruses

Transmission is by respiratory droplets. Tropism is respiratory epithelium, with a particular and clinically defining tropism for the laryngeal and upper tracheal region in young children.

Parainfluenza is the classic and dominant cause of croup, laryngotracheobronchitis, in young children, producing the characteristic barking cough, inspiratory stridor, and hoarseness reflecting upper airway and subglottic narrowing and inflammation. It also causes more generalised upper and lower respiratory illness across age groups, generally milder in adults.

Diagnosis is predominantly clinical for typical croup, with PCR respiratory panel testing where broader viral identification is clinically indicated.

Respiratory syncytial virus

Transmission is by respiratory droplets and direct or fomite contact, given a degree of environmental surface persistence unusual for an enveloped virus, relevant to healthcare-associated and nursery or childcare transmission. Tropism is lower respiratory tract epithelium, bronchioles particularly, directly explaining its characteristic disease pattern and distinguishing its typical severity profile from the more upper-tract-predominant parainfluenza viruses.

RSV is the leading cause of bronchiolitis and viral lower respiratory tract infection in infants, producing wheeze, respiratory distress, and, in severe cases, respiratory failure.

Respiratory failure occurs particularly in young infants, especially those born prematurely or with underlying cardiopulmonary disease. At the other end of the age spectrum, RSV is increasingly recognised as a significant cause of morbidity and mortality in frail elderly patients.

The syncytium formation from which the virus takes its name is a classic histopathological and cytopathic finding.

Diagnosis relies on rapid antigen testing and PCR from a nasopharyngeal specimen, both widely used given the clinical urgency of confirming the diagnosis in unwell infants. Monoclonal antibody prophylaxis is available for specific high-risk infant populations, a notable point of contrast with most other respiratory viruses, for which no equivalent passive prophylaxis exists.