Within-host antigenic selection of influenza A virus dominates over stochasticity but is limited by fitness tradeoffs and timing of the immune response
Despite antigenic evolution at the global scale, positive selection of influenza virus antigenic variants is not readily observed within hosts. Here, we tested the extent to which fitness tradeoffs, the timing of immune pressure, and stochastic effects impede antigenic selection within pre-immune hosts. We used genetically barcoded influenza A/Texas/50/2012 (H3N2) viruses (Tx/12) in a guinea pig…
Within-host antigenic selection of influenza A virus significantly surpasses stochastic effects, although it is constrained by fitness trade-offs and the timing of immune responses. Despite global-scale antigenic evolution, such positive selection within hosts is not frequently observed. Researchers employed genetically marked influenza A/Texas/50/2012 (H3N2) viruses, known as Tx/12, in guinea pigs to examine these processes.
The emergence of an antigenic variant within the infected host depended on a strong immune pressure early in the infection course. However, when the fitness costs associated with the antigenic change were reduced, a weaker and later onset of immune pressure could still support the variant. Regardless of the conditions, the study found that stochastic effects played a moderate role in the evolution of the virus.
The researchers concluded that the rarity of antigenic escape is likely due to a limited mutational pool, fitness trade-offs, and the inherent delay between infection and antibody production.
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