Abstract：
Wild birds are the reservoir for all avian influenza viruses (AIV). In poultry, the transition from low pathogenic (LP) AIV of H5 and H7 subtypes to highly pathogenic (HP) AIV is accompanied mainly by changing the hemagglutinin (HA) monobasic cleavage site (CS) to a polybasic motif (pCS). Galliformes, including turkeys and chickens, succumb with high morbidity and mortality to HPAIV infections, although turkeys appear more vulnerable than chickens. Surprisingly, the genetic determinants for virulence and pathogenesis of HPAIV in turkeys are largely unknown. Here, we determined the genetic markers for virulence and transmission of HPAIV H7N1 in turkeys, and we explored the host responses in this species compared to those of chickens. We found that recombinant LPAIV H7N1 carrying pCS was avirulent in chickens but exhibited high virulence in turkeys, indicating that virulence determinants vary in these two galliform species. A transcriptome analysis indicated that turkeys mount a different host response than do chickens, particularly from genes involved in RNA metabolism and the immune response. Furthermore, we found that the HA glycosylation at residue 123, acquired by LP viruses shortly after transmission from wild birds and preceding the transition from LP to HP, had a role in virus fitness and virulence in chickens, though it was not a prerequisite for high virulence in turkeys. Together, these findings indicate variable virulence determinants and host responses in two closely related galliformes, turkeys and chickens, after infection with HPAIV H7N1. These results could explain the higher vulnerability to HPAIV of turkeys compared to chickens. IMPORTANCE Infection with HPAIV in chickens and turkeys, two closely related galliform species, results in severe disease and death. Although the presence of a polybasic cleavage site (pCS) in the hemagglutinin of AIV is a major virulence determinant for the transition of LPAIV to HPAIV, there are knowledge gaps on the genetic determinants (including pCS) and the host responses in turkeys compared to chickens. Here, we found that the pCS alone was sufficient for the transformation of a LP H7N1 into a HPAIV in turkeys but not in chickens. We also noticed that turkeys exhibited a different host response to an HPAIV infection, namely, a widespread downregulation of host gene expression associated with protein synthesis and the immune response. These results are important for a better understanding of the evolution of HPAIV from LPAIV and of the different outcomes and the pathomechanisms of HPAIV infections in chickens and turkeys.
摘要：
野生鸟类是所有禽流感病毒（AIV）的宿主。在家禽中，从H5和H7亚型的低致病性（LP）AIV过渡到高致病性（HP）AIV主要伴随着将血凝素（HA）单碱基裂解位点（CS）改变为多基序（pCS）。Galliformes,包括火鸡和鸡,HPAIV感染的高发病率和高死亡率，虽然火鸡看起来比鸡更脆弱。令人惊讶的是,火鸡中HPAIV毒力和发病机制的遗传决定因素尚不清楚.这里,我们确定了HPAIVH7N1在火鸡中的毒力和传播的遗传标记，我们探索了该物种与鸡的宿主反应。我们发现携带pCS的重组LPAIVH7N1在鸡中无毒，但在火鸡中表现出高毒力，表明毒力决定因素在这两个galliform物种中有所不同。转录组分析表明，火鸡的宿主反应与鸡不同，特别是涉及RNA代谢和免疫反应的基因。此外，我们发现，在从野生鸟类传播后不久，在从LP到HP的过渡之前，由LP病毒获得的123残基HA糖基化，在鸡的病毒适应性和毒力中起作用，尽管这不是火鸡高毒力的先决条件。一起,这些发现表明在两个密切相关的galliformes中可变的毒力决定子和宿主反应，火鸡和鸡,感染HPAIVH7N1后。这些结果可以解释与鸡相比，火鸡对HPAIV的脆弱性更高。鸡和火鸡感染HPAIV的重要性，两个密切相关的galliform物种，导致严重的疾病和死亡。尽管在AIV的血凝素中存在多碱基切割位点（pCS）是LPAIV向HPAIV过渡的主要毒力决定因素，与鸡相比，火鸡在遗传决定因素（包括pCS）和宿主反应方面存在知识差距。这里,我们发现，仅pCS就足以将火鸡中的LPH7N1转化为HPAIV，而不是鸡。我们还注意到，火鸡对HPAIV感染表现出不同的宿主反应，即,与蛋白质合成和免疫反应相关的宿主基因表达的广泛下调。这些结果对于更好地了解HPAIV从LPAIV的演变以及鸡和火鸡中HPAIV感染的不同结果和病理机制非常重要。
