Question
Antigenic variation in influenza virus
Answer
Antigenic variation in influenza virus occurs through two distinct mechanisms affecting the surface antigens haemagglutinin (HA) and neuraminidase (NA):
Antigenic drift: gradual, minor accumulation of point mutations in the HA/NA genes (due to the error-prone viral RNA polymerase lacking proofreading), occurring in both influenza A and B; responsible for seasonal epidemics and the need for annual vaccine reformulation, since partial cross-reactive immunity from prior exposure/vaccination is progressively eroded but not eliminated.
Antigenic shift: a major, abrupt change in HA/NA through genetic reassortment — exchange of whole gene segments between two different strains co-infecting the same host cell (e.g., in a pig “mixing vessel”) — occurring only in influenza A, since it requires an animal reservoir; produces a completely novel HA/NA combination against which the population has little/no pre-existing immunity, capable of causing a pandemic (e.g., 1918 H1N1, 1957 H2N2, 1968 H3N2, 2009 H1N1).
Basis for both mechanisms: influenza A’s segmented RNA genome (8 gene segments) is what permits reassortment (shift); the intrinsically error-prone RNA-dependent RNA polymerase, lacking proofreading capability, is what drives the ongoing accumulation of point mutations (drift).