Abstract
Our overall hypothesis is that host population immunity directed at multiple antigens will influence the prevalence, diversity and evolution of influenza A virus (IAV) in avian populations where the vast subtype diversity is maintained. To investigate how initial infection influences the outcome of later infections with homologous or heterologous IAV subtypes and how viruses interact through host immune responses, we carried out experimental infections in mallard ducks (Anas platyrhynchos). Mallards were pre-challenged with an H3N8 low-pathogenic IAV and were divided into six groups. At five weeks post H3N8 inoculation, each group was challenged with a different IAV subtype (H4N5, H10N7, H6N2, H12N5) or the same H3N8. Two additional pre-challenged groups were inoculated with the homologous H3N8 virus at weeks 11 and 15 after pre-challenge to evaluate the duration of protection. The results showed that mallards were still resistant to re-infection after 15 weeks. There was a significant reduction in shedding for all pre-challenged groups compared to controls and the outcome of the heterologous challenges varied according to hemagglutinin (HA) phylogenetic relatedness between the viruses used. There was a boost in the H3 antibody titer after re-infection with H4N5, which is consistent with original antigenic sin or antigenic seniority and suggest a putative strategy of virus evasion. These results imply competition between related subtypes that could regulate IAV subtype population dynamics in nature. Collectively, we provide new insights into within-host IAV complex interactions as drivers of IAV antigenic diversity that could allow the circulation of multiple subtypes in wild ducks.
Highlights
Diversification is a common feature in pathogen populations and this often involves the evolution of antigenic variants [1]
Influenza A viruses (IAVs) can infect many avian and mammalian hosts, but while few influenza A virus (IAV) subtypes circulate in human populations, subtype diversity is extensive in wild bird populations
How do these subtypes coexist in wild avian populations and do they compete within these natural host populations? Here we experimentally challenged mallard ducks with different IAVs to study how an initial infection with H3N8 determines the outcome of later infections and antibody responses
Summary
Diversification is a common feature in pathogen populations and this often involves the evolution of antigenic variants [1] Examples of this exist in various pathogen systems: viruses (influenza A virus, Dengue virus, Bluetongue virus, and rotaviruses), bacteria (Borrelia spp, Neisseria meningitis, and Pneumococcus) and protozoan parasites (Plasmodium spp. and trypanosomes). Shared epitopes between different HA subtypes associated with the HA stalk have been described and these may be important target epitopes for universal IAV vaccines. Immunity to these shared epitopes may provide partial protection in subsequent infections with heterologous IAV [2] and could potentially influence clinical outcome and regulate subtype diversity in host populations through competition [3]
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