IHAP, Toulouse University, ENVT, INRAE, Toulouse, France.
Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Vet Res. 2022 Feb 14;53(1):11. doi: 10.1186/s13567-022-01028-x.
In late 2015, an epizootic of Highly Pathogenic Avian Influenza (H5Nx) was registered in Southwestern France, including more than 70 outbreaks in commercial poultry flocks. Phylogenetic analyses suggested local emergence of H5 viruses which differed from A/goose/Guangdong/1/1996 clade 2.3.4.4b lineage and shared a unique polybasic cleavage site in their hemagglutinin protein. The present work provides an overview of the pathobiological picture associated with this epizootic in naturally infected chickens, guinea fowls and ducks. Upon necropsy examination, selected tissues were sampled for histopathology, immunohistochemistry and quantitative Real Time Polymerase Chain Reaction. In Galliformes, HPAIVs infection manifested as severe acute systemic vasculitis and parenchymal necrosis and was associated with endothelial expression of viral antigen. In ducks, lesions were mild and infrequent, with sparse antigenic detection in respiratory and digestive mucosae and leukocytes. Tissue quantifications of viral antigen and RNA were higher in chickens and guinea fowls compared to duck. Subsequently, recombinant HA (rHA) was generated from a H5 HPAIV isolated from an infected duck to investigate its glycan-binding affinity for avian mucosae. Glycan-binding analysis revealed strong affinity of rHA for 3'Sialyl-LacNAc and low affinity for Sialyl-Lewis, consistent with a duck-adapted virus similar to A/Duck/Mongolia/54/2001 (H5N2). K222R and S227R mutations on rHA sequence shifted affinity towards Sialyl-Lewis and led to an increased affinity for chicken mucosa, confirming the involvement of these two mutations in the glycan-binding specificity of the HA. Interestingly, the rHA glycan binding pattern of guinea fowl appeared intermediate between duck and chicken. The present study presents a unique pathobiological description of the H5 HPAIVs outbreaks that occurred in 2015-2016 in Southwestern France.
2015 年末，法国西南部爆发了高致病性禽流感（HPAI）疫情，包括商业家禽养殖场爆发了 70 多起疫情。系统发育分析表明，当地出现的 H5 病毒与 A/goose/Guangdong/1/1996 分支 2.3.4.4b 谱系不同，其血凝素蛋白具有独特的多碱性裂解位点。本研究概述了 2015-2016 年法国西南部爆发的 H5 高致病性禽流感疫情在自然感染鸡、珍珠鸡和鸭中的病理生物学特征。剖检时，选择组织进行组织病理学、免疫组织化学和定量实时聚合酶链反应分析。在鸡中，HPAIV 感染表现为严重的急性全身性血管炎和实质坏死，并与病毒抗原在内皮细胞的表达相关。在鸭中，病变较轻且不常见，呼吸道和消化道黏膜和白细胞中稀疏检测到抗原。与鸭相比，鸡和珍珠鸡组织中病毒抗原和 RNA 的定量更高。随后，从感染鸭中分离出的 H5 高致病性禽流感病毒生成了重组 HA（rHA），以研究其对禽黏膜的糖结合亲和力。糖结合分析表明，rHA 对 3'Sialyl-LacNAc 具有很强的亲和力，对 Sialyl-Lewis 的亲和力较低，与类似于 A/Duck/Mongolia/54/2001（H5N2）的鸭适应病毒一致。rHA 序列上的 K222R 和 S227R 突变使亲和力向 Sialyl-Lewis 转移，并导致对鸡黏膜的亲和力增加，证实了这两个突变参与了 HA 的糖结合特异性。有趣的是，珍珠鸡 rHA 的糖结合模式介于鸭和鸡之间。本研究对 2015-2016 年法国西南部爆发的 H5 高致病性禽流感疫情进行了独特的病理生物学描述。
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