37. Orthomyxoviridae. The causative agents of flu. Paramyxoviridae. The causative agents of paraflu, epidemic parotitis, and measles. Respiratory syncytial virus. Coronaviruses. SARS- CoV-2 and the disease COVID-19.

I. General Characteristics

• Belongs to Family Orthomyxoviridae.
• Enveloped, single-stranded, negative-sense RNA virus.
• Genome is segmented (8 segments in Influenza A & B).
• Helical nucleocapsid, surrounded by lipid envelope.
• Replicates in the nucleus (unique among RNA viruses).
• Three main types:
• Influenza A: infects humans, birds, pigs, etc. → causes pandemics.
• Influenza B: only in humans → seasonal epidemics.
• Influenza C: mild illness, rarely causes epidemics.

III. Antigenic Variation

• Antigenic drift:
• Minor mutations in HA or NA genes.
• Occurs in Influenza A and B.
• Causes seasonal epidemics.
• Antigenic shift:

• Sudden reassortment of gene segments between different Influenza A strains.
• Leads to new HA and/or NA subtypes.
• Responsible for pandemics (e.g., 2009 H1N1).

IV. Epidemiology

• Reservoir: humans (A, B, C), animals (A: birds, pigs).
• Transmission: respiratory droplets, direct contact.
• Seasonality: Winter in temperate regions.
• Incubation: 1–4 days.
• High risk: elderly, children, immunocompromised, pregnant women.

V. Pathogenesis

• Inhaled virus infects respiratory epithelial cells.
• HA binds to sialic acid receptors → endocytosis.
• M2 protein acidifies endosome → viral uncoating.
• Replication in host nucleus → viral RNA polymerase synthesizes mRNA.
• Destruction of respiratory epithelium:
• ↓ mucociliary clearance → risk of secondary bacterial infections.
• Inflammatory cytokine release → systemic symptoms (fever, myalgia).