A large effective population size for established within-host influenza virus infection

Abstract

Strains of the influenza virus form coherent global populations, yet exist at the level of single infections in individual hosts. The relationship between these scales is a critical topic for understanding viral evolution. Here we investigate the within-host relationship between selection and the stochastic effects of genetic drift, estimating an effective population size of infection Ne for influenza infection. Examining whole-genome sequence data describing a chronic case of influenza B in a severely immunocompromised child we infer an Ne of 2.5 x 107 (95% confidence range 1.0 x 107 to 9.0 x 107) suggesting that genetic drift is of minimal importance during an established influenza infection. Our result, supported by data from influenza A infection, suggests that positive selection during within-host infection is primarily limited by the typically short period of infection. Atypically long infections may have a disproportionate influence upon global patterns of viral evolution.

Asynchrony between virus diversity and antibody selection limits influenza virus evolution

“…We find that replication selection of antigenic novelty to detectable levels becomes likely only if infections are prolonged, and virus antigenic diversity and antibody selection pressure therefore coincide ( Figure 1G , see also Figure 7). This can explain existing observations: within-host adaptive antigenic evolution can be seen in prolonged infections of immune-compromised hosts ( Xue et al, 2017 ), and prolonged influenza infections show large within-host effective population sizes ( Lumby et al, 2020 ).…”

“…Those authors studied ferret transmission experiments and partitioned selection for adaptive mutants (not necessarily antigenic) into selection for transmissibility (acting at a potentially tight bottleneck) and selection during exponential growth. Subsequently, several studies have hypothesized that influenza virus antigenic selection might be weak in short-lived infections of individual experienced hosts and might occur at the point of transmission ( Petrova and Russell, 2018 ; Han et al, 2019 ; Lumby et al, 2020 ).…”

“…Hosts who develop less specific memory responses, such as very young children ( Neuzil et al, 2006 ), could be less important. Similarly, immune-compromised hosts are excellent replication selectors ( Xue et al, 2017 ; Lumby et al, 2020 ), and so their role in the generation of antigenic novelty and their impact on overall population-level diversification rates deserve further study.…”

Asynchrony between virus diversity and antibody selection limits influenza virus evolution

“…Those authors studied ferret transmission experiments and partitioned selection for adaptive mutants (not necessarily antigenic) into selection for transmissibility (acting at a potentially tight bottleneck) and selection during exponential growth. Subsequently, several studies have hypothesized that influenza virus antigenic selection might be weak in short-lived infections of individual experienced hosts and might occur at the point of transmission (Petrova and Russell, 2018;Han et al, 2019;Lumby et al, 2020). To our knowledge, however, ours is the first study to undertake a mechanistic, model-based comparison between the role of antigenic selection at the point of transmission and that of antigenic selection during replication, to show that immunologically plausible mechanisms could make the former more salient than the latter, and to connect that finding to the rarity of observable new antigenic variants in homotypically reinfected human hosts.…”

“…Hosts who develop less specific memory responses, such as very young children (Neuzil et al, 2006), could be less important. Similarly, immune-compromised hosts are excellent replication selectors (Xue et al, 2017;Lumby et al, 2020), and so their role in the generation of antigenic novelty and their impact on overall population-level diversification rates deserve further study.…”