Ecological and immunological determinants of influenza evolution

Abstract

In pandemic and epidemic forms, influenza causes substantial, sometimes catastrophic, morbidity and mortality. Intense selection from the host immune system drives antigenic change in influenza A and B, resulting in continuous replacement of circulating strains with new variants able to re-infect hosts immune to earlier types. This 'antigenic drift' often requires a new vaccine to be formulated before each annual epidemic. However, given the high transmissibility and mutation rate of influenza, the constancy of genetic diversity within lineages over time is paradoxical. Another enigma is the replacement of existing strains during a global pandemic caused by 'antigenic shift'--the introduction of a new avian influenza A subtype into the human population. Here we explore ecological and immunological factors underlying these patterns using a mathematical model capturing both realistic epidemiological dynamics and viral evolution at the sequence level. By matching model output to phylogenetic patterns seen in sequence data collected through global surveillance, we find that short-lived strain-transcending immunity is essential to restrict viral diversity in the host population and thus to explain key aspects of drift and shift dynamics.

Seasonal influenza in the United States, France, and Australia: transmission and prospects for control

“…This difference in transmissibility could be attributed to underlying differences in the age patterns of infection among influenza (sub)types. Influenza A/H3N2 viruses have the fastest evolutionary rates [59], causing re-infection of a single individual with the same subtype multiple times through life, thereby allowing for a larger pool of susceptibles, and higher transmissibility. By contrast, B viruses have the slowest evolutionary rate [59] and infect mainly children [60], perhaps explaining their lower transmissibility.…”

“…Influenza A/H3N2 viruses have the fastest evolutionary rates [59], causing re-infection of a single individual with the same subtype multiple times through life, thereby allowing for a larger pool of susceptibles, and higher transmissibility. By contrast, B viruses have the slowest evolutionary rate [59] and infect mainly children [60], perhaps explaining their lower transmissibility. A/H1N1 viruses have intermediate evolutionary rate [59] and did not display a clear relationship with transmissibility in our study.…”

“…By contrast, B viruses have the slowest evolutionary rate [59] and infect mainly children [60], perhaps explaining their lower transmissibility. A/H1N1 viruses have intermediate evolutionary rate [59] and did not display a clear relationship with transmissibility in our study. Our finding of increased transmissibility of A/H3N2 viruses reinforces a recent study showing more rapid dispersal of A/H3N2 epidemics across the United States, as compared with A/H1N1-B epidemics [18].…”

Shaping the phylogenetic tree of influenza by cross-immunity

“…Ferguson et al (2003) and Tria et al (2005) The strain that is first introduced in the population can be considered to be the next generation of the a-lineage, while the strain that is introduced later will be referred to as the b-strain. Now imagine that strain a has already made an epidemic and that strain b comes to the population.…”

“…Because of the multiple strains and the complexities of the population based herd-immunity, an account for the transmission dynamics and mutation process sufficiently detailed to reproduce the drift-like behavior seems to require individual based computer simulations (Ferguson et al, 2003;Tria et al, 2005). To avoid the complexities of such models we will not attempt to include all processes involved in influenza drift but rather study branching as "a perturbation off" the normal drift process.…”