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

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.

Avian H7N9 influenza viruses are evolutionarily constrained by stochastic processes during replication and transmission in mammals

“…This level of within-host diversity is not unexpected in animals directly inoculated with a high-dose viral isolate ( Wilker et al. 2013 ; Leyson et al. 2022 ).…”

Avian H7N9 influenza viruses are evolutionarily constrained by stochastic processes during replication and transmission in mammals

“…Anhui/1 (n=5 ferrets) had an average of 152 iSNVs per animal, ranging from 85-195, while GD/3 (n=5 ferrets) had an average of 109 iSNVs per ferret, ranging from 27-142 across all timepoints. This level of within-host diversity is not unexpected in animals directly inoculated with a high-dose viral isolate 36,37 . The number of iSNVs found in each animal fluctuates over time and often trends downward in GD/3 and Anhui/1 donor ferrets ( Supplementary Figure 2 ).…”