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Title: Adaptive heterosubtypic immunity to low pathogenic avian influenza viruses in experimentally infected mallards

Author
item SEGOVIA, KAREN - University Of Georgia
item STALKNECHT, DAVID - University Of Georgia
item Kapczynski, Darrell
item STABLER, LISA - University Of Georgia
item BERGHAUS, ROY - University Of Georgia
item FOTJIK, ALINDE - University Of Georgia
item LATORRE-MARGALEF, NEUS - University Of Georgia
item FRANCA, MONIQUE - University Of Georgia

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/3/2017
Publication Date: 1/20/2017
Citation: Segovia, K.M., Stalknecht, D.E., Kapczynski, D.R., Stabler, L., Berghaus, R.D., Fotjik, A., Latorre-Margalef, N., Franca, M.S. 2017. Adaptive heterosubtypic immunity to low pathogenic avian influenza viruses in experimentally infected mallards. PLoS One. 12(1):e0170335. doi:10.1371/journal.pone.0170335.

Interpretive Summary: Mallard ducks constitute the main reservoir for low pathogenic avian influenza viruses (AIV) in nature and differences in prevalence of viral subtypes are likely influenced by immunity in these birds. Heterosubtypic immunity refers to the ability to protect against different AIV subtypes. Under experimental conditions, we assessed the magnitude of the heterosubtypic immunity induced by infection with an H3N8 AIV against similar (H4N6) or less prevalent subtypes (H10N7 and H14N5) AIV in mallards at different time intervals. Furthermore, we evaluated if subsequent inoculations with different AIV subtypes would have a boosting effect in the magnitude of heterosubtypic immunity. Here, we demonstrate that inoculation with the H3N8 AIV induced heterosubtypic immunity and that cross protection followed the genetic relatedness between the AIVs tested. In addition, the magnitude of heterosubtypic immunity was increased with multiple subsequent infections. Our findings offer possible explanations to the dynamics of AIV subtype diversity in mallards.

Technical Abstract: Mallards are widely recognized as reservoirs for Influenza A viruses (IAV), however host factors that might prompt seasonality and trends in subtype diversity of IAV such as adaptive heterosubtypic immunity (HSI) are not well understood. We inoculated mallards with a prevailing H3N8 low pathogenic avian influenza virus (LPAIV) subtype in waterfowl to determine if prior infection with this virus would be protective against heterosubtypic infections with the H4N6, H10N7 and H14N5 LPAIV subtypes after one, two and three months, respectively. In addition, we investigated the effect of cumulative immunity after sequential inoculation of mallards with these viruses in one month intervals. Humoral immunity was assessed by micro neutralization assays using a subset of representative LPAIV subtypes as antigens. Our results indicate that prior inoculation with the H3N8 virus confers partial protective immunity against subsequent heterosubtypic infections with robustness of HSI related to the phylogenetic similarity of the HA protein of the strains used. Furthermore, induced HSI was boosted following exposure to more than one LPAIV subtype. Our findings provide further information and understanding on the contributions of HSI and its role in the dynamics of IAV subtype diversity in mallards.