Antigenic drift

Not to be confused with Antigenic shift or Genetic drift.

Antigenic drift is a mechanism for variation in viruses that involves the accumulation of mutations within the genes that code for antibody-binding sites. This results in a new strain of virus particles which cannot be inhibited as effectively by the antibodies that were originally targeted against previous strains, making it easier for the virus to spread throughout a partially immune population. Antigenic drift occurs in both influenza A and influenza B viruses.

The immune system recognizes viruses when antigens on the surfaces of virus particles bind to immune receptors that are specific for these antigens. This is similar to a lock recognizing a key. After an infection, the body produces many more of these virus-specific immune receptors, which prevent re-infection by this particular strain of the virus and produce acquired immunity. Similarly, a vaccine against a virus works by teaching the immune system to recognize the antigens exhibited by this virus. However, viral genomes are constantly mutating, producing new forms of these antigens. If one of these new forms of an antigen is sufficiently different from the old antigen, it will no longer bind to the receptors and viruses with these new antigens can evade immunity to the original strain of the virus. When such a change occurs, people who have had the illness in the past are nevertheless not immune to the new strain and thus the vaccines against the original virus will be less effective against the illness. Two processes drive the antigens to change: antigenic drift and antigenic shift, antigenic drift being the more common. The rate of antigenic drift is dependent on two characteristics: the duration of the epidemic, and the strength of host immunity. A longer epidemic allows for selection pressure to continue over an extended period of time and stronger host immune responses increase selection pressure for development of novel antigens.

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 neuraminidase 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.

See also

• Antigenic shift

External links

• An illustration of antigenic drift
• A technical definition