Mutation and Epistasis in Influenza Virus Evolution

Abstract

Influenza remains a persistent public health challenge, because the rapid evolution of influenza viruses has led to marginal vaccine efficacy, antiviral resistance, and the annual emergence of novel strains. This evolvability is driven, in part, by the virus’s capacity to generate diversity through mutation and reassortment. Because many new traits require multiple mutations and mutations are frequently combined by reassortment, epistatic interactions between mutations play an important role in influenza virus evolution. While mutation and epistasis are fundamental to the adaptability of influenza viruses, they also constrain the evolutionary process in important ways. Here, we review recent work on mutational effects and epistasis in influenza viruses.

Small-Molecule Antiviral β- d - N 4 -Hydroxycytidine Inhibits a Proofreading-Intact Coronavirus with a High Genetic Barrier to Resistance

“…If this is the case, mutations promoting NHC resistance would need to arise early during passage to help mitigate the accumulation of excess deleterious mutations. Alternatively, the inability to evade inhibition by NHC may lead to the accumulation of a greater number of NHC-associated transitions and ultimately a higher mutational burden that may impact viral fitness (64,65). Together, our results support the hypothesis that establishment of resistance to NHC in CoVs requires a delicate balance of resistance-promoting mutations, viral fitness, and accumulation of deleterious mutations.…”

CD‐sACE2 inclusion compounds: An effective treatment for coronavirus disease 2019 (COVID‐19)

“…Virus mutations seriously affect the therapeutic effects of antiviral drugs and the preventive effect of vaccines. 10 The application of sACE2 can potentially prevent the viruses from infecting healthy cells by binding to the S-proteins of the virus and destroying its ability to mutate. All the ACE2-receptor viruses can be blocked by sACE2.…”

Identification of lncRNA‐155 encoded by MIR155HG as a novel regulator of innate immunity against influenza A virus infection

“…Coinfection of a particular host can give rise to genetically different population of influenza virus via de novo mutations and genetic reassortment (Lyons & Lauring, 2018;Nelson & Holmes, 2007;Schmolke & Garcia-Sastre, 2010). Coinfection of a particular host can give rise to genetically different population of influenza virus via de novo mutations and genetic reassortment (Lyons & Lauring, 2018;Nelson & Holmes, 2007;Schmolke & Garcia-Sastre, 2010).…”

“…Various hosts may support the constant evolution and circulation of IAVs. Coinfection of a particular host can give rise to genetically different population of influenza virus via de novo mutations and genetic reassortment (Lyons & Lauring, 2018;Nelson & Holmes, 2007;Schmolke & Garcia-Sastre, 2010). This unique IAV evolution style makes the annually local formulated vaccines be variably effective (Pica & Palese, 2013) and leads to the emergence of drug-resistant strains, rendering some of the available anti-influenza virus drugs to be ineffective over time (Hurt, 2014).…”