Zoe Gleason, Class of 2023
Influenza is a common respiratory virus that affects 5-20% of the United States population yearly. The virion of the influenza virus, which is composed of an outer protein shell and an inner nucleic acid, is typically spherical in shape and is surrounded by a lipid membrane. Surface proteins project outwards from this membrane. The two major surface proteins of the influenza virus are hemagglutinin and neuraminidase. According to the Centers for Disease Control (CDC), these proteins are considered antigens, meaning that the immune system can recognize them and trigger an immune response that can produce antibodies to block the infection (2019). The antibodies in our bodies respond to the presence of the virus and interact with the surface proteins. However, if the surface proteins change, the antibodies in our immune system from previous exposures to influenza will not recognize the virus and will not be able to enact as effective of a response. A change in the surface proteins is known as antigenic evolution.
Antigenic evolution has two major components, antigenic drift and antigenic shift. Antigenic drift is small changes that result in very similar viruses. In this case, the immune system can often use antibodies made when exposed to a similar virus. However, antigenic drifts can accumulate to result in a virus that is very different from the original, resulting in an unprepared immune response (CDC 2019). Antigenic shift is a major change in the virus, often due to the virus passing from animals to humans (CDC 2019). In the influenza virus, this results in a change in the surface proteins. Antigenic shift occurs less frequently than antigenic drift, but can have greater effects, as most people have no immunity towards the new influenza viruses due to the change in surface proteins. Additionally, antigenic shift can cause flu vaccines to be less effective, because they respond to the original surface proteins. These factors can lead to influenza pandemics.
Epistasis is the genetic interactions between mutations in a genome and their subsequent expression levels (Lyons and Lauring 2018). Most frequently, epistasis occurs between two mutations. When a mutation occurs within the genome, this can cause additional mutations to occur in what is known as an epistasis cluster. This growing amount of mutations is thought to be the cause of antigenic drift. Epistasis can also lead to evolution since it factors into the fitness level of the organism or virus.
Epistasis can occur positively or negatively. Positive epistasis is when the compilation of beneficial mutations results in an increase in fitness. This increase in fitness must be greater than the increase experienced when the two mutations are both present, but not interacting with each other. On the other hand, if deleterious mutations are combined under positive epistasis, their decrease in fitness level would be smaller than expected. Positive epistasis can be recorded by the appearance of a second mutation near the site of the first one more quickly than would be expected (Lyons and Lauring 2018). Positive epistasis will increase influenza’s function when it is between beneficial mutations and will lessen the severity of decrease in function when it is between deleterious mutations.
Negative epistasis is the exact opposite of positive epistasis. In this case, when two mutations are combined, a smaller than expected increase in fitness would be seen between beneficial mutations and a greater than expected decrease in fitness would be seen between deleterious mutations. Negative epistasis is important to the survival of the influenza virus because combining deleterious mutations will result in these mutations quickly being purged from the population. This would increase the average fitness level of the influenza virus (Lyons and Lauring 2018).
Mutations within the influenza virus are important because they can affect the surface proteins, hemagglutinin and neuraminidase. Changes in the surface proteins affects the response by the immune system since large changes will prevent any antibodies present from recognizing the virus. Antibodies may still recognize influenza when altered from antigenic drift, but are not likely to recognize it when altered from antigenic shift. Antigenic shift and drift are thought to be caused by epistasis clusters. Epistasis can have different effects on the virus depending on if it is positive or negative epistasis. Positive epistasis will protect deleterious mutations from being removed from the genome, and negative epistasis will cause these mutations to be purged faster from the genome. Epistasis will affect the evolution of the influenza virus since it plays an important role in the fitness level of the virus.
References
Daniel M. Lyons and Adam S. Lauring. Mutation and Epistasis in Influenza Virus Evolution. Viruses. 2018 Aug. http://dx.doi.org/10.3390/v10080407. doi:10.3390/v10080407
How the Flu Virus Can Change: “Drift” and “Shift.” Centers for Disease Control and Prevention. 2019 Oct [accessed 2021 Feb 22]. https://www.cdc.gov/flu/about/viruses/change.htm
Antigenic evolution has two major components, antigenic drift and antigenic shift. Antigenic drift is small changes that result in very similar viruses. In this case, the immune system can often use antibodies made when exposed to a similar virus. However, antigenic drifts can accumulate to result in a virus that is very different from the original, resulting in an unprepared immune response (CDC 2019). Antigenic shift is a major change in the virus, often due to the virus passing from animals to humans (CDC 2019). In the influenza virus, this results in a change in the surface proteins. Antigenic shift occurs less frequently than antigenic drift, but can have greater effects, as most people have no immunity towards the new influenza viruses due to the change in surface proteins. Additionally, antigenic shift can cause flu vaccines to be less effective, because they respond to the original surface proteins. These factors can lead to influenza pandemics.
Epistasis is the genetic interactions between mutations in a genome and their subsequent expression levels (Lyons and Lauring 2018). Most frequently, epistasis occurs between two mutations. When a mutation occurs within the genome, this can cause additional mutations to occur in what is known as an epistasis cluster. This growing amount of mutations is thought to be the cause of antigenic drift. Epistasis can also lead to evolution since it factors into the fitness level of the organism or virus.
Epistasis can occur positively or negatively. Positive epistasis is when the compilation of beneficial mutations results in an increase in fitness. This increase in fitness must be greater than the increase experienced when the two mutations are both present, but not interacting with each other. On the other hand, if deleterious mutations are combined under positive epistasis, their decrease in fitness level would be smaller than expected. Positive epistasis can be recorded by the appearance of a second mutation near the site of the first one more quickly than would be expected (Lyons and Lauring 2018). Positive epistasis will increase influenza’s function when it is between beneficial mutations and will lessen the severity of decrease in function when it is between deleterious mutations.
Negative epistasis is the exact opposite of positive epistasis. In this case, when two mutations are combined, a smaller than expected increase in fitness would be seen between beneficial mutations and a greater than expected decrease in fitness would be seen between deleterious mutations. Negative epistasis is important to the survival of the influenza virus because combining deleterious mutations will result in these mutations quickly being purged from the population. This would increase the average fitness level of the influenza virus (Lyons and Lauring 2018).
Mutations within the influenza virus are important because they can affect the surface proteins, hemagglutinin and neuraminidase. Changes in the surface proteins affects the response by the immune system since large changes will prevent any antibodies present from recognizing the virus. Antibodies may still recognize influenza when altered from antigenic drift, but are not likely to recognize it when altered from antigenic shift. Antigenic shift and drift are thought to be caused by epistasis clusters. Epistasis can have different effects on the virus depending on if it is positive or negative epistasis. Positive epistasis will protect deleterious mutations from being removed from the genome, and negative epistasis will cause these mutations to be purged faster from the genome. Epistasis will affect the evolution of the influenza virus since it plays an important role in the fitness level of the virus.
References
Daniel M. Lyons and Adam S. Lauring. Mutation and Epistasis in Influenza Virus Evolution. Viruses. 2018 Aug. http://dx.doi.org/10.3390/v10080407. doi:10.3390/v10080407
How the Flu Virus Can Change: “Drift” and “Shift.” Centers for Disease Control and Prevention. 2019 Oct [accessed 2021 Feb 22]. https://www.cdc.gov/flu/about/viruses/change.htm
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