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.

Highlights

  • RNA viruses are known to have high mutation rates and short generation times.at any given time, viruses can be considered as populations of genetic variants [1,2]

  • Virus-inoculated turkeys transmitted the viruses to all contacts regardless of the virus doses tested, whereas transmission was only observed in chickens inoculated with either of the two LPAIVs at the highest virus doses tested

  • These results demonstrate that turkeys are more susceptible to the 2020 H7N3 viruses compared to chickens [35]

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Summary

Introduction

At any given time, viruses can be considered as populations of genetic variants [1,2]. Variants that are present at a low frequency can replicate exponentially and quickly become predominant in the population. The existence of such variants in a population allows for rapid response to prevailing circumstances and thereby can potentially lead to the emergence of new viral strains [3,4]. Viral genetic diversity can be examined at various timescales. Because within-host virus diversity can be considered as the foundation from which the genetic diversity originates across time and space, investigating at the within-host level enables us to explore virus evolution in its earliest stages, soon after infecting a host

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