The evolution of seasonal influenza viruses

Key Points The evolution of seasonal influenza viruses is an important source of disease burden, as it allows for the reinfection of previously infected or vaccinated individuals Given that 5–15% of the global human population is infected with seasonal influenza viruses each year, it is surprising that new antigenic variants arise only every 3–5 years for A/H3N2 viruses and less frequently for A/H1N1 and B viruses The virus surface glycoprotein haemagglutinin is the primary target of the host immune response, and evolutionary selection pressure drives it to acquire mutations to escape immune recognition without eliminating its receptor binding function Host immunity has a dual role in governing the pace of virus evolution: innate immunity acts as a constraint on the generation of new virus variants, whereas adaptive immunity selects for immune escape mutants The acute nature of influenza virus infections and population-level epidemics provides limited opportunities for evolutionary selection, with most virus diversity being lost before selection can operate Influenza virus vaccines can provide effective protection against infection when they are well matched to circulating viruses, but there remains scope for improving vaccine production and delivery to achieve better effectiveness Seasonal influenza viruses continue to cause epidemics each year. In this Review, Petrova and Russell discuss recent advances in understanding the molecular determinants of influenza virus immune escape, sources of evolutionary selection pressure, population dynamics of influenza viruses and prospects for better influenza virus control. Despite decades of surveillance and pharmaceutical and non-pharmaceutical interventions, seasonal influenza viruses continue to cause epidemics around the world each year. The key process underlying these recurrent epidemics is the evolution of the viruses to escape the immunity that is induced by prior infection or vaccination. Although we are beginning to understand the processes that underlie the evolutionary dynamics of seasonal influenza viruses, the timing and nature of emergence of new virus strains remain mostly unpredictable. In this Review, we discuss recent advances in understanding the molecular determinants of influenza virus immune escape, sources of evolutionary selection pressure, population dynamics of influenza viruses and prospects for better influenza virus control.