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Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies

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Clonal interference in the evolution of influenza.

Natalja Strelkowa¹, Michael Lässig

¹Department of Bioengineering, Imperial College London, South Kensington, United Kingdom.

|August 2, 2012

Summary

Seasonal influenza A virus evolves rapidly through strong clonal interference, a competitive process between viral strains. This explains the observed evolutionary patterns and highlights the interplay between immune adaptation and viral function conservation.

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Area of Science:

Virology
Evolutionary Biology
Genomics

Background:

Influenza A virus rapidly evolves to evade the human immune system.
Adaptive mutations primarily target antigenic epitopes in the hemagglutinin protein.
Recurrent selective sweeps, occurring approximately every 4 years, are observed in influenza A evolution.

Purpose of the Study:

To investigate the evolutionary dynamics of influenza A (H3N2) virus.
To determine if clonal interference explains the observed selective sweep patterns.
To understand the interplay between immune adaptation and other viral functions in influenza evolution.

Main Methods:

Analysis of single-nucleotide polymorphism frequency time series.
Utilized 39 years of influenza genome sequence data.
Inferred selection and clonal interference based on evolutionary patterns.

Main Results:

Influenza A (H3N2) evolution is characterized by strong clonal interference.
Clonal interference explains the observed selective sweep patterns.
An average of one beneficial amino acid substitution per year and 3–4 driving mutations per sweep were identified.

Conclusions:

Both immune adaptation and background selection outside epitopes govern influenza evolution.
Interference between immune adaptation and viral function conservation impacts viral protein stability.
A comprehensive understanding of influenza dynamics requires considering all genomic domains and functions, coupled with clonal interference.