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Marked neurotropism and potential adaptation of H5N1 clade 2.3.4.4.b virus in naturally infected domestic cats.
Emerging Microbes & Infections ( IF 8.4 ) Pub Date : 2024-12-17 , DOI: 10.1080/22221751.2024.2440498
Shubhada K Chothe,Surabhi Srinivas,Sougat Misra,Noel Chandan Nallipogu,Elizabeth Gilbride,Lindsey LaBella,Swastidipa Mukherjee,Christian H Gauthier,Heidi L Pecoraro,Brett T Webb,James M Pipas,Santhamani Ramasamy,Suresh V Kuchipudi

In April 2024, ten cats died in a rural South Dakota (SD) residence, showing respiratory and neurological symptoms. Necropsy and laboratory testing of two cats confirmed H5N1 clade 2.3.4.4b infection. The viral genome sequences are closely related to recent SD cattle H5N1 sequences. Cat H5N1 genomes had unique mutations, including T143A in haemagglutinin, known to affect infectivity and immune evasion, and two novel mutations in PA protein (F314L, L342Q) that may affect polymerase activity and virulence, suggesting potential virus adaptation. Dead cats showed systemic infection with lesions and viral antigens in multiple organs. Higher viral RNA and antigen in the brain indicated pronounced neurotropism. Lectin-histochemistry revealed widespread co-expression of sialic acid α-2,6 and α-2,3 receptors, suggesting cats could serve as mixing vessels for reassortment of avian and mammalian influenza viruses. No differences in clade 2.2 or 2.3.4.4b H5 pseudoviruses binding to cat lung/brain tissues indicated the neurotropism is unlikely mediated by receptor binding affinity.

中文翻译:


H5N1 分支 2.3.4.4.b 病毒在自然感染的家猫中具有显著的嗜神经性和潜在适应性。



2024 年 4 月,10 只猫在南达科他州 (SD) 的农村住宅中死亡,出现呼吸道和神经系统症状。对两只猫的尸检和实验室检查证实了 H5N1 分支 2.3.4.4b 感染。病毒基因组序列与最近的 SD 牛 H5N1 序列密切相关。猫 H5N1 基因组具有独特的突变,包括血凝素中的 T143A,已知会影响感染性和免疫逃逸,以及 PA 蛋白中的两种新突变 (F314L、L342Q),可能影响聚合酶活性和毒力,表明潜在的病毒适应。死猫表现为全身感染,多器官病变和病毒抗原。大脑中较高的病毒 RNA 和抗原表明明显的嗜神经性。凝集素组织化学显示唾液酸 α-2,6 和 α-2,3 受体的广泛共表达,表明猫可以作为禽流感病毒和哺乳动物流感病毒重组的混合容器。进化枝 2.2 或 2.3.4.4b H5 假病毒与猫肺/脑组织结合没有差异,表明神经嗜性不太可能由受体结合亲和力介导。
更新日期:2024-12-09
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