Contact between bird species of different lifespans can promote the emergence of highly pathogenic avian influenza strains

Outbreaks of highly pathogenic strains of avian influenza viruses (AIVs) cause considerable economic losses to the poultry industry and also pose a threat to human life. The possibility that one of these strains will evolve to become transmissible between humans, sparking a major influenza pandemic, is a matter of great concern. Most studies so far have focused on assessing these odds from the perspective of the intrinsic mutability of AIV rather than the ecological constraints to invasion faced by the virus population. Here we present an alternative multihost model for the evolution of AIV in which the mode and tempo of mutation play a limited role, with the emergence of strains being determined instead principally by the prevailing profile of population-level immunity. We show that (i) many of the observed differences in influenza virus dynamics among species can be captured by our model by simply varying host lifespan and (ii) increased contact between species of different lifespans can promote the emergence of potentially more virulent strains that were hitherto suppressed in one of the species.Avian influenza viruses (AIVs) exist within a complex ecology that includes common interspecies transmission among birds (1, 2). Like all influenza viruses, AIV can be divided into subtypes (e.g., H5N1) on the basis of variation in the hemagglutinin (HA) and neuraminidase (NA) surface proteins and also exhibit extensive antigenic diversity within a particular subtype (e.g., refs. 3 and 4). Most AIV cocirculating between domestic and wild birds are classified as being of low pathogenicity (LPAIV). Occasionally, however, highly pathogenic (HPAIV) forms arise, causing high mortality in poultry. Severe illness and death also occur in humans infected by HPAIV: There have been around 650 human cases of subtype H5N1 HPAIV, with 384 deaths, since 2003. However, a recent epidemic of subtype H7N9 LPAIV, which has to date claimed more than 100 lives from ∼400 confirmed cases, illustrates that inducing severe disease in humans is not the sole preserve of HPAIV.In avian species other than domestic poultry, AIV infection is largely asymptomatic (5, 6) with the notable exception of HP H5N1, which has caused recorded deaths in domestic and exotic waterfowl. Among ducks, the outcome of HP H5N1 infection is variable (7–11) and several factors suggest that domestic ducks may act as an asymptomatic reservoir (or “Trojan horse”) (12–14). Since 2002, HP H5N1 viruses have been regularly found among wild birds, including various species of migratory ducks and geese (15) in Asia, but other HPAIV have been isolated only sporadically from wildfowl (e.g., ref. 7).HP H5N1 was first isolated in 1997 from chickens, ducks, and geese but the direction of transmission among these species remains unclear (16, 17). By contrast, genetic analyses of the virus responsible for the 2013 H7N9 outbreak show that virus to have moved first from wild birds to geese and ducks and then to chickens (18). Such studies offer insights into the dispersal history of AIV but they do not explain why new viral lineages or strains associated with phenotypes of interest (including, but not limited to, pathogenicity) arise and spread. The current understanding is that their emergence is limited by the occurrence of mutational events that are assumed to be rare (4, 19), but this is not wholly consistent with both the high observed rates of AIV nucleotide substitution (20) and the fact that many viral phenotypes are defined by a small number of genetic changes (21): Changes at as few as seven amino acid sites can explain recent patterns of antigenic evolution in humans (22). Here, we show many of these questions can be answered by recognizing that the virus population comprises a large pool of interchangeable gene segments (2) circulating within a variety of wild and domestic species of widely different lifespans. We demonstrate that host lifespan is a key determinant of the population dynamics of the virus and that the emergence of particular phenotypes may be driven by the immunodynamics of multispecies transmission rather than by the generation of those phenotypes by mutation.