Review Article | Published:

The evolution of seasonal influenza viruses

Nature Reviews Microbiology volume 16, pages 4760 (2018) | Download Citation

  • An Erratum to this article was published on 07 November 2017

This article has been updated

Abstract

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.

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

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Change history

  • 07 November 2017

    In Figure 4 of the original online version of the article, the influenza virus epidemic activity by month was incorrectly labelled. This has now been corrected in the online and print versions. We apologize to the authors and to readers for any confusion caused.

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Acknowledgements

The authors thank A. Han for his help with Fig. 1b–e. This work was supported by a Wellcome Trust Ph.D. Studentship to V.N.P. and by a Royal Society University Research Fellowship and a Wellcome Trust Collaborative Award to C.A.R.

Author information

Author notes

    • Colin A. Russell

    Present address: Laboratory of Applied Evolutionary Biology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands

Affiliations

  1. Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.

    • Velislava N. Petrova
  2. Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, UK.

    • Colin A. Russell

Authors

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Contributions

V.N.P. and C.A.R. contributed to researching data for article. V.N.P. and C.A.R. substantially contributed to the discussion of content. V.N.P. and C.A.R. wrote the article. V.N.P. and C.A.R. reviewed and edited the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Colin A. Russell.

Glossary

Epidemics

Infectious disease outbreaks involving a large number of people in a defined geographic location over a defined period of time.

Fomites

Surfaces or objects that can be contaminated by pathogens.

Pandemics

Global infectious disease epidemics.

Genome reassortment

A form of genomic rearrangement where two or more influenza viruses infect the same cell and exchange genomic segments, resulting in a genetically novel virus.

Antigenic clusters

A set of influenza virus variants with similar antigenic profiles.

Haemagglutination inhibition (HAI) assays

Experimental assays used to antigenically characterize viruses based on the ability of host serum to inhibit the virus-induced agglutination of red blood cells.

Within-host selection

Evolutionary selection that occurs at the level of an individual host, generally pertaining to virus fitness or virus interaction with the host immune response.

Immunodominant

A property of an antigen, causing it to be the primary focus of the immune response.

Plaque assays

Experimental assays that measure virus growth rates.

Microneutralization assays

Experimental assays that measure the ability of host serum to neutralize specific antigenic strains.

Deep mutational scanning

An experimental protocol for assessing the mutability and effect of amino acid substitutions at specific positions or across entire proteins.

Epitopes

The parts of an antigen that are recognized by the host adaptive immune response.

Antigenicity

The quality determining the appearance of an antigen to the immune system.

Avidity

The strength of binding between an antigen and a receptor based on multiple chemical bonds.

Dynamical models

A mathematical abstraction of the time-dependent behaviour of an object or system.

Mucociliary clearance

The removal of pathogens by the movement of mucus in the upper respiratory tract by ciliated cells.

Infectious dose

The number of pathogen particles that initiate an infection.

Antigenic distance

A measure of antigenic similarity derived from quantitative representations of haemagglutination inhibition assay data.

Immune waning

The process by which antibody titres or general immune reactivity declines with time in the absence of stimulation.

Immunological backboosting

The recall of previously acquired immune memory upon infection or vaccination with a partially cross-reactive antigen.

Antigenic seniority

The phenomenon of having higher antibody titres to influenza virus variants encountered earlier in life than to more recent viruses.

Bottlenecks

Contractions in population diversity associated with reductions in population size.

Adjuvant

A pharmacological agent that affects the breadth and/or strength of the immune response.

Antisera

The antibody-containing portions of the blood, which are specific for a given pathogen.

Immune repertoire sequencing

Targeted genetic sequencing of the B cell or T cell receptor genes.

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DOI

https://doi.org/10.1038/nrmicro.2017.118

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