Key Laboratory of Jiangsu Preventive Veterinary Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
J Virol. 2023 Feb 28;97(2):e0137922. doi: 10.1128/jvi.01379-22. Epub 2023 Feb 7.
Despite active control strategies, including the vaccination program in poultry, H9N2 avian influenza viruses possessing mutations in hemagglutinin (HA) were frequently isolated. In this study, we analyzed the substitutions at HA residue 193 (H3 numbering) of H9N2 and investigated the impact of these mutations on viral properties. Our study indicated that H9N2 circulating in the Chinese poultry have experienced frequent mutations at HA residue 193 since 2013, with viruses that carried asparagine (N) being replaced by those with alanine (A), aspartic acid (D), glutamic acid (E), glycine (G), and serine (S), etc. Our results showed the N193G mutation impeded the multiple cycles of growth of H9N2, and although most of the variant HAs retained the preference for human-like receptors as did the wild-type N193 HA, the N193E mutation altered the preference for both human and avian-like receptors. Furthermore, these mutations substantially altered the antigenicity of H9N2 as measured by both monoclonal antibodies and antisera. studies further demonstrated that these mutations showed profound impact on viral replication and transmission of H9N2 in chicken. Viruses with D, E, or S at residue 193 acquired the ability to replicate in lungs of the infected chickens, whereas virus with G193 reduced its transmissibility in infected chickens to those in direct contact. Our findings demonstrated that variations at HA residue 193 altered various properties of H9N2, highlighting the significance of the continued surveillance of HA for better understanding of the etiology and effective control of H9N2 in poultry. H9N2 are widespread and have sporadically caused clinical diseases in humans. Extensive vaccinations in poultry helped constrain H9N2; however, they might have facilitated the evolution of the virus. It is therefore of importance to monitor the variation of the circulating H9N2 and evaluate its risk to both veterinary and public health. Here, we found substitutions at position 193 of HA from H9N2 circulated since 2013 and assessed the impact of several mutations on viral properties. Our data showed these mutations resulted in substantial antigenic change. N193E altered the binding preference of HA for human-like to both avian and human-like receptors. More importantly, N193G impaired the growth of H9N2 and its transmission in chickens, whereas mutations from N to D, E, and S enhanced the viral replication in lungs of chickens. Our study enriched the knowledge about H9N2 and may help implement an effective control strategy for H9N2.
尽管采取了积极的控制策略，包括在禽类中实施疫苗接种计划，但具有血凝素（HA）突变的 H9N2 禽流感病毒仍频繁被分离出来。在这项研究中，我们分析了 H9N2 中 HA 残基 193（H3 编号）的取代情况，并研究了这些突变对病毒特性的影响。我们的研究表明，自 2013 年以来，在中国禽类中传播的 H9N2 经历了 HA 残基 193 的频繁突变，携带天冬酰胺（N）的病毒被取代为丙氨酸（A）、天冬氨酸（D）、谷氨酸（E）、甘氨酸（G）和丝氨酸（S）等。我们的结果表明，N193G 突变阻碍了 H9N2 的多次生长循环，尽管大多数变体 HA 保留了对人类样受体的偏好，就像野生型 N193 HA 一样，但 N193E 突变改变了对人类和禽类样受体的偏好。此外，这些突变极大地改变了 H9N2 的抗原性，这一点通过单克隆抗体和抗血清都得到了证实。进一步的研究表明，这些突变对 H9N2 在鸡中的复制和传播产生了深远的影响。在残基 193 处具有 D、E 或 S 的病毒获得了在感染鸡肺部复制的能力，而具有 G193 的病毒降低了其在感染鸡中的传染性，使其与直接接触的鸡相比传染性降低。我们的发现表明，HA 残基 193 的变异改变了 H9N2 的各种特性，强调了继续监测 HA 的重要性，以便更好地了解 H9N2 的病因学和在禽类中进行有效控制。H9N2 广泛传播，并偶尔在人类中引起临床疾病。在禽类中广泛接种疫苗有助于限制 H9N2 的传播；然而，这可能促进了病毒的进化。因此，监测循环 H9N2 的变异并评估其对兽医和公共卫生的风险非常重要。在这里，我们发现自 2013 年以来流通的 H9N2 中 HA 的位置 193 发生了取代，并评估了几种突变对病毒特性的影响。我们的数据表明，这些突变导致了显著的抗原变化。N193E 改变了 HA 对人类样受体的结合偏好，使其对禽类和人类样受体都具有亲和力。更重要的是，N193G 阻碍了 H9N2 的生长及其在鸡中的传播，而 N 突变为 D、E 和 S 增强了病毒在鸡肺部的复制。我们的研究丰富了对 H9N2 的认识，并可能有助于实施针对 H9N2 的有效控制策略。
