Antigenic Drift - in Influenza Viruses

In Influenza Viruses

In the influenza virus, the two relevant antigens are the surface proteins, hemagglutinin and neuraminidase. The hemagglutinin is responsible for binding and entry into host epithelial cells while the neuraminidase is involved in the process of new virions budding out of host cells. Sites recognized on the hemagglutinin and neuraminidase proteins by host immune systems are under constant selective pressure. Antigenic drift allows for evasion of these host immune systems by small mutations in the hemagglutinin and neraminidase genes that make the protein unrecognizable to pre-existing host immunity. Antigenic drift is this continuous process of genetic and antigenic change among flu strains.

In human populations, immune (vaccinated) individuals exert selective pressure for single point mutations in the hemagglutinin gene that increase receptor binding avidity, while naive individuals exert selective pressure for single point mutations that decrease receptor binding avidity. These dynamic selection pressures facilitate the observed rapid evolution in the hemagglutinin gene. Specifically, 18 specific codons in the HA1 domain of the hemagglutinin gene have been identified as undergoing positive selection to change their encoded amino acid. To meet the challenge of antigenic drift, vaccines that confer broad protection against heterovariant strains are needed against seasonal, epidemic and pandemic influenza.

As in all RNA viruses, mutations in influenza occur frequently because the virus' RNA polymerase has no proofreading mechanism, resulting in an error rate between 1×10−3 and 8×10−3 substitutions per site per year during viral genome replication. Mutations in the surface proteins allow the virus to elude some host immunity, and the numbers and locations of these mutations that confer the greatest amount of immune escape has been an important topic of study for over a decade.

Antigenic drift has been responsible for heavier-than-normal flu seasons in the past, like the outbreak of influenza H3N2 variant A/Fujian/411/2002 in the 2003–2004 flu season. All influenza viruses experience some form of antigenic drift, but it is most pronounced in the influenza A virus.

Antigenic drift should not be confused with antigenic shift, which refers to reassortment of the virus' gene segments. As well, it is different from random genetic drift, which is an important mechanism in population genetics.