TY - JOUR
T1 - Competition between influenza A virus subtypes through heterosubtypic immunity modulates re-infection and antibody dynamics in the mallard duck
AU - Latorre-Margalef, Neus
AU - Brown, Justin D.
AU - Fojtik, Alinde
AU - Poulson, Rebecca L.
AU - Carter, Deborah
AU - Franca, Monique
AU - Stallknecht, David E.
N1 - Funding Information:
NLM was funded by International Postdoc Grants from The Wenner-Gren Foundations, Stockholm, Sweden and the Swedish Research Council, VR (2013-7510). The research was funded by CEIRS, NIH, US under the contract HHSN272201400006C to DES. The funding agencies were not involved in the design, implementation, or publishing of this study and the research presented herein represents the opinions of the authors, but not necessarily the opinions of the funding agencies. We thank Morgan J. Slusher for assistance with sampling and animal care, as well to the BSL2+ animal facilities at PDRC and Animal Resources at the College of Veterinary Medicine, UGA. Thanks also to Clara Kienzle and Nick Davis-Fields for technical assistance in the laboratory and to Alexis Avril and Camille Lebarbenchon for discussions and statistical advice. We are grateful to three anonymous reviewers for constructive review comments.
Publisher Copyright:
© 2017 Latorre-Margalef et al.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85021835573&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021835573&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1006419
DO - 10.1371/journal.ppat.1006419
M3 - Article
C2 - 28640898
AN - SCOPUS:85021835573
SN - 1553-7366
VL - 13
JO - PLoS pathogens
JF - PLoS pathogens
IS - 6
M1 - e1006419
ER -