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Antigenic drift is a kind of genetic variation in viruses, arising from the accumulation of
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...
s in the virus genes that code for virus-surface proteins that host
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
recognize. This results in a new strain of virus particles that is not effectively inhibited by the antibodies that prevented infection by previous strains. This makes it easier for the changed virus to spread throughout a partially immune population. Antigenic drift occurs in both and viruses. (Confusion can arise with two very similar terms,
antigenic shift Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains. The term is ...
and
genetic drift Genetic drift, also known as allelic drift or the Wright effect, is the change in the frequency of an existing gene variant (allele) in a population due to random chance. Genetic drift may cause gene variants to disappear completely and there ...
. Antigenic shift is a closely related process; it refers to more dramatic changes in the virus's surface proteins. Genetic drift is very different and much more broadly applicable; it refers to the gradual accumulation in any DNA sequence of random mutational changes that do not interfere with the DNA's function and thus that are not seen by
natural selection Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Cha ...
.) The
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
recognizes viruses when
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...
s on the surfaces of virus particles bind to
immune receptor An immune receptor (or immunologic receptor) is a receptor, usually on a cell membrane, which binds to a substance (for example, a cytokine) and causes a response in the immune system. Types The main receptors in the immune system are patter ...
s that are specific for these antigens. These receptors can be antibodies in the bloodstream or similar proteins on the surfaces of immune-system cells. This recognition is quite precise, like a key recognizing a lock. After an
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
or after
vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulat ...
, the body produces many more of these virus-specific immune receptors, which prevent re-infection by this particular strain of the virus; this is called acquired immunity. However, viral genomes are constantly
mutating In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...
, 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 antibodies or immune-cell receptors, allowing the mutant virus to infect people who were immune to the original strain of the virus because of prior infection or vaccination. In 1940s, Maurice Hilleman discovered antigenic drift, which is the most common way that influenza viruses change. A second type of change is
antigenic shift Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains. The term is ...
, also discovered by Hilleman, where the virus acquires a completely new version of one of its surface-protein genes from a distantly related influenza virus. 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 Any cause that reduces or increases reproductive success in a portion of a population potentially exerts evolutionary pressure, selective pressure or selection pressure, driving natural selection. It is a quantitative description of the amount of ...
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 ''Orthomyxoviridae'' (from Greek ὀρθός, ''orthós'' 'straight' + μύξα, ''mýxa'' 'mucus') is a family of negative-sense RNA viruses. It includes seven genera: ''Alphainfluenzavirus'', ''Betainfluenzavirus'', '' Gammainfluenzavirus'', ' ...
, the two relevant antigens are the surface proteins,
hemagglutinin In molecular biology, hemagglutinins (or ''haemagglutinin'' in British English) (from the Greek , 'blood' + Latin , 'glue') are receptor-binding membrane fusion glycoproteins produced by viruses in the '' Paramyxoviridae'' family. Hemagglutinins a ...
and
neuraminidase Exo-α-sialidase (EC 3.2.1.18, sialidase, neuraminidase; systematic name acetylneuraminyl hydrolase) is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids: : Hydrolysis of α-(2→3)-, α-(2→6)-, α-(2→8)- glyc ...
. The hemagglutinin is responsible for binding and entry into host epithelial cells while the neuraminidase is involved in the process of new
virion A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's ...
s 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 The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
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 ''Orthornavirae'' is a kingdom of viruses that have genomes made of ribonucleic acid (RNA), those genomes encoding an RNA-dependent RNA polymerase (RdRp). The RdRp is used to transcribe the viral RNA genome into messenger RNA (mRNA) and to ...
, mutations in influenza occur frequently because the virus'
RNA polymerase In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens th ...
has no proofreading mechanism, resulting in an error rate between and substitutions per site per year during viral genome replication. Mutations in the surface proteins allow the virus to elude some host
immunity Immunity may refer to: Medicine * Immunity (medical), resistance of an organism to infection or disease * ''Immunity'' (journal), a scientific journal published by Cell Press Biology * Immune system Engineering * Radiofrequence immunity de ...
, 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 Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains. The term is ...
, 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 Population genetics is a subfield of genetics that deals with genetic differences within and between populations, and is a part of evolutionary biology. Studies in this branch of biology examine such phenomena as adaptation, speciation, and po ...
.


See also

*
Antigenic shift Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains. The term is ...
*
Original antigenic sin Original antigenic sin, also known as antigenic imprinting, the Hoskins effect, or immunological imprinting, is the propensity of the immune system to preferentially use immunological memory based on a previous infection when a second slightly di ...


Notes


Further reading

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External links


An illustration of antigenic drift

A technical definition
{{DEFAULTSORT:Antigenic Drift Virology Influenza