Orthomyxoviruses

Orthomyxoviruses (family Orthomyxoviridae) are enveloped viruses whose genome consists of segmented, negative-sense, single-stranded RNA. The medically important members are the influenza viruses — types A, B, and C — with influenza A responsible for the most severe disease and all pandemics. Unusually for an RNA virus, influenza replicates in the host cell's nucleus.

Two envelope glycoproteins drive both infection and immunity. Hemagglutinin (HA) binds sialic acid receptors on respiratory epithelium to gain entry, while neuraminidase (NA) cleaves sialic acid to release newly formed virions from the cell surface. Influenza A subtypes are named for these proteins — H1N1, H3N2, and so on — and they are the targets of the immune response and of antiviral drugs in the neuraminidase-inhibitor class.

The viruses evolve by two distinct mechanisms. Antigenic drift is the gradual accumulation of point mutations in HA and NA, producing the seasonal changes that require annual vaccine updates and cause epidemics. Antigenic shift occurs only in influenza A: because the genome comes in eight separate segments, two strains co-infecting one host (often via animal reservoirs like birds and pigs) can swap whole segments — reassortment — creating a novel subtype to which the population has little immunity. Shift is the mechanism behind pandemics.

Orthomyxoviruses are core virology material on the USMLE Step 1, which tests the segmented negative-sense RNA genome, the functions of hemagglutinin and neuraminidase, drift versus shift, and complications such as secondary bacterial pneumonia following influenza.