与越南H5N1分离株相比，牛H5N1在C57BL/6J小鼠中具有更强的嗜神经性。
Enhanced neurotropism of bovine H5N1 compared to the Vietnam H5N1 isolate in C57BL/6J mice.
作者信息
Goldin Kerry, van Tol Sarah, Johnson Randall C, Mukesh Reshma Koolaparambil, Cooper Kendal G, Gallogly Shane, Schulz Jonathan E, Prado-Smith Jessica, Martens Craig, Saturday Greg, Yinda Kwe Claude, Munster Vincent J, de Wit Emmie, van Doremalen Neeltje
机构信息
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Research Technology Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
出版信息
Npj Viruses. 2025 May 23;3(1):43. doi: 10.1038/s44298-025-00121-0.
In this study, we investigated differences in tissue tropism of two HPAI H5N1 strains, the isolate A/Vietnam/1203/2004 (VN1203) isolated from a fatal human case in 2004 and the bovine isolate A/Bovine/Ohio/B24osu-342/2024 (Bov342) isolated in 2024, in C57BL/6J mice. Infection via aerosols was uniformly lethal in mice. However, tissue tropism differed significantly: while VN1203 replication was largely restricted to the respiratory tract, Bov342 successfully replicated in the respiratory tract as well as various regions of the brain. Correspondingly, cytokine profiles in the brain differed significantly between the isolates. Notably, in addition to abundant evidence of CNS infection in Bov342-challenged mice via immunohistochemistry, sporadic intranuclear and intracytoplasmic immunoreactivity was observed in other tissues in the head, including the choroid plexus, retina, and inner ear. This study demonstrates that while both HPAI H5N1 isolates are uniformly lethal in C57BL/6J mice upon aerosol exposure, significant differences exist in tissue tropism.
在本研究中，我们调查了两种高致病性禽流感H5N1毒株在C57BL/6J小鼠中的组织嗜性差异，这两种毒株分别是2004年从一例致命人类病例中分离出的A/越南/1203/2004（VN1203）以及2024年分离出的牛源毒株A/牛/俄亥俄/B24osu - 342/2024（Bov342）。通过气溶胶感染对小鼠具有一致的致死性。然而，组织嗜性存在显著差异：虽然VN1203的复制主要局限于呼吸道，但Bov342不仅在呼吸道成功复制，还在大脑的各个区域进行了复制。相应地，两种毒株在大脑中的细胞因子谱也存在显著差异。值得注意的是，除了通过免疫组织化学在感染Bov342的小鼠中发现大量中枢神经系统感染的证据外，在头部的其他组织，包括脉络丛、视网膜和内耳中，还观察到散在的核内和胞浆内免疫反应性。本研究表明，虽然两种高致病性禽流感H5N1毒株经气溶胶暴露后对C57BL/6J小鼠均具有一致的致死性，但它们在组织嗜性上存在显著差异。
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