Antigenic drift
Encyclopedia
The immune system
recognizes viruses when antigen
s 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 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 will lose their immunity to the new strain and vaccines against the original virus will also become less effective. 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.
A mechanism for variation by viruses that involves the accumulation of mutations within the antibody-binding sites so that the resulting viruses cannot be inhibited well by antibodies against previous strains making it easier for them to spread throughout a partially immune population. Antigenic drift occurs in both influenza A and influenza B viruses
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 neraminidase proteins by host immune systems are under constant selective pressure. Antigenic shift 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 1x10^-3 and 8x10^-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 season
s 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
.
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
recognizes viruses when antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s 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 receptors, which prevent re-infection by this particular strain
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...
of the virus and produce acquired immunity. Similarly, a vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
against a virus works by teaching the immune system to recognize the antigens exhibited by this virus. However, viral genomes are constantly mutating
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
, 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 will lose their immunity to the new strain and vaccines against the original virus will also become less effective. Two processes drive the antigens to change: antigenic drift and antigenic shift
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...
, 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.
A mechanism for variation by viruses that involves the accumulation of mutations within the antibody-binding sites so that the resulting viruses cannot be inhibited well by antibodies against previous strains making it easier for them to spread throughout a partially immune population. Antigenic drift occurs in both influenza A and influenza B viruses
In influenza viruses
In the influenza virus, the two relevant antigens are the surface proteins, hemagglutininHemagglutinin
Influenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected...
and neuraminidase
Neuraminidase
Neuraminidase enzymes are glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread...
. 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 neraminidase proteins by host immune systems are under constant selective pressure. Antigenic shift 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 1x10^-3 and 8x10^-3 substitutions per site per year during viral genome replication. Mutations in the surface proteins allow the virus to elude some host immunity
Immunity (medical)
Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...
, 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 season
Flu season
Flu season is a annually-recurring time period characterized by the prevalence of outbreaks of influenza . The season occurs during the cold half of the year in each hemisphere. Influenza activity can sometimes be predicted and even tracked geographically...
s 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
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...
, 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
Population genetics is the study of allele frequency distribution and change under the influence of the four main evolutionary processes: natural selection, genetic drift, mutation and gene flow. It also takes into account the factors of recombination, population subdivision and population...
.