Low pathogenicity H7N3 avian influenza viruses have higher within-host genetic diversity than a closely related high pathogenicity H7N3 virus in infected turkeys and chickens

Authors: LEYSON, CHRISTINA - Orise Fellow; CRIADO, MIRIA - Consultant; YOUK, SUNGSU - Orise Fellow; Pantin Jackwood, Mary

Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/3/2022
Publication Date: 3/8/2022
Citation: Leyson, C.M., Criado, M.F., Youk, S., Pantin Jackwood, M.J. 2022. Low pathogenicity H7N3 avian influenza viruses have higher within-host genetic diversity than a closely related high pathogenicity H7N3 virus in infected turkeys and chickens. Viruses. 14(3):554. https://doi.org/10.3390/v14030554.
DOI: https://doi.org/10.3390/v14030554

Interpretive Summary: In order to understand the evolution of avian influenza viruses (AIV's), we examined within-host virus diversity in turkeys and chickens experimentally infected with a high pathogenicity AIV (HPAIV) or one of two low pathogenicity AIV's (LPAIV's). For this, we conducted virus sequencing from samples obtained from the experimentally infected birds. The diversity of viral genomes was examined and compared to provide insights into AIV populations in the birds. Consistent with the high mutation rates of AIV's, an abundance of changes, known as single nucleotide variants (SNV), was observed in all samples but at low frequencies. Also, a small number of common SNV's were observed between turkeys and chickens, or between directly virus inoculated birds and contact-exposed birds. Notably, the LPAIV's had significantly higher SNV diversities than the HPAIV in turkeys and chickens. These findings help us understand what happens to AIV populations within different hosts which can affect the evolution of the virus.

Technical Abstract: Within-host viral diversity offers a view into the early stages of viral evolution occurring after a virus infects a host. In recent years, advances in deep sequencing have allowed for routine identification of low-frequency variants, which are important sources of viral genetic diversity and can potentially emerge as a major virus population under certain conditions. We examined within-host viral diversity in turkeys and chickens experimentally infected with closely related H7N3 avian influenza viruses (AIVs), specifically one high pathogenicity AIV (HPAIV) and two low pathogenicity AIV (LPAIVs) with different neuraminidase protein stalk lengths. Consistent with the high mutation rates of AIVs, an abundance of intra-host single nucleotide variants (iSNVs) at low frequencies of 2–10% was observed in all samples collected. Furthermore, a small number of common iSNVs were observed between turkeys and chickens, and between directly inoculated and contact-exposed birds. Notably, the LPAIVs have significantly higher iSNV diversities and frequencies of nonsynonymous changes than the HPAIV in both turkeys and chickens. These findings highlight the dynamics of AIV populations within hosts and the potential impact of genetic changes, including mutations in the hemagglutinin gene that confers the high pathogenicity pathotype, on AIV virus populations and evolution.