Ecole Nationale Vétérinaire de Toulouse, Université de Toulouse, ENVT, INRAE, IHAP, UMR 1225, Toulouse, France.
J Virol. 2022 Jan 12;96(1):e0136621. doi: 10.1128/JVI.01366-21. Epub 2021 Oct 6.
Highly pathogenic avian influenza viruses (HPAIV) emerge from low-pathogenic avian influenza viruses (LPAIV) through the introduction of basic amino acids at the hemagglutinin (HA) cleavage site. Following viral evolution, the newly formed HPAIV likely represents a minority variant within the index host, predominantly infected with the LPAIV precursor. Using reverse genetics-engineered H5N8 viruses differing solely at the HA cleavage, we tested the hypothesis that the interaction between the minority HPAIV and the majority LPAIV could modulate the risk of HPAIV emergence and that the nature of the interaction could depend on the host species. In chickens, we observed that the H5N8 increased H5N8 replication and pathogenesis. In contrast, the H5N8 antagonized H5N8 replication and pathogenesis in ducks. Ducks mounted a more potent antiviral innate immune response than chickens against the H5N8, which correlated with H5N8 inhibition. These data provide experimental evidence that HPAIV may be more likely to emerge in chickens than in ducks and underscore the importance of within-host viral variant interactions in viral evolution. Highly pathogenic avian influenza viruses represent a threat to poultry production systems and to human health because of their impact on food security and because of their zoonotic potential. It is therefore crucial to better understand how these viruses emerge. Using a within-host competition model between high- and low-pathogenic avian influenza viruses, we provide evidence that highly pathogenic avian influenza viruses could be more likely to emerge in chickens than in ducks. These results have important implications for highly pathogenic avian influenza virus emergence prevention, and they underscore the importance of within-host viral variant interactions in virus evolution.
高致病性禽流感病毒 (HPAIV) 通过在血凝素 (HA) 裂解位点引入碱性氨基酸从低致病性禽流感病毒 (LPAIV) 中出现。在病毒进化之后，新形成的 HPAIV 可能代表索引宿主中的少数变异体，主要感染 LPAIV 前体。使用仅在 HA 裂解处不同的反向遗传工程 H5N8 病毒，我们测试了这样一种假设，即少数 HPAIV 与多数 LPAIV 之间的相互作用可以调节 HPAIV 出现的风险，并且相互作用的性质可能取决于宿主物种。在鸡中，我们观察到 H5N8 增加了 H5N8 的复制和发病机制。相比之下，H5N8 在鸭中拮抗 H5N8 的复制和发病机制。与鸡相比，鸭对 H5N8 产生了更强的抗病毒先天免疫反应，这与 H5N8 的抑制作用相关。这些数据提供了实验证据，表明 HPAIV 可能更容易在鸡中出现，而不是在鸭中出现，并强调了宿主内病毒变异体相互作用在病毒进化中的重要性。高致病性禽流感病毒因其对食品安全的影响以及潜在的人畜共患病性，对家禽生产系统和人类健康构成威胁。因此，更好地了解这些病毒如何出现至关重要。使用高致病性和低致病性禽流感病毒在宿主内的竞争模型，我们提供了证据表明，高致病性禽流感病毒可能更容易在鸡中出现，而不是在鸭中出现。这些结果对高致病性禽流感病毒出现的预防具有重要意义，并且强调了宿主内病毒变异体相互作用在病毒进化中的重要性。
