Transmission of a human isolate of clade 2.3.4.4b A(H5N1) virus in ferrets

IF 50.5 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Nature Pub Date : 2024-10-28 DOI:10.1038/s41586-024-08246-7
Joanna A. Pulit-Penaloza, Jessica A. Belser, Nicole Brock, Troy J. Kieran, Xiangjie Sun, Claudia Pappas, Hui Zeng, Paul Carney, Jessie Chang, Brandon Bradley-Ferrell, James Stevens, Juan A. De La Cruz, Yasuko Hatta, Han Di, C. Todd Davis, Terrence M. Tumpey, Taronna R. Maines
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Abstract

Since 2020, there has been unprecedented global spread of highly pathogenic avian influenza A(H5N1) in wild bird populations with spillover into a variety of mammalian species and sporadically humans1. In March 2024, clade 2.3.4.4b A(H5N1) virus was first detected in dairy cattle in the USA, with subsequent detection in numerous states2, leading to more than a dozen confirmed human cases3,4. In this study, we used the ferret, a well-characterized animal model that permits concurrent investigation of viral pathogenicity and transmissibility5, in the evaluation of A/Texas/37/2024 (TX/37) A(H5N1) virus isolated from a dairy farm worker in Texas6. Here we show that the virus has a remarkable ability for robust systemic infection in ferrets, leading to high levels of virus shedding and spread to naive contacts. Ferrets inoculated with TX/37 rapidly exhibited a severe and fatal infection, characterized by viraemia and extrapulmonary spread. The virus efficiently transmitted in a direct contact setting and was capable of indirect transmission through fomites. Airborne transmission was corroborated by the detection of infectious virus shed into the air by infected animals, albeit at lower levels compared to those of the highly transmissible human seasonal and swine-origin H1 subtype strains. Our results show that despite maintaining an avian-like receptor-binding specificity, TX/37 exhibits heightened virulence, transmissibility and airborne shedding relative to other clade 2.3.4.4b virus isolated before the 2024 cattle outbreaks7, underscoring the need for continued public health vigilance. Analysis of a human isolate of the A/Texas/37/2024 strain of highly pathogenic avian influenza A(H5N1) virus in the ferret model demonstrates its pathogenicity and transmission in both direct and indirect contact settings, including airborne transmission.

Abstract Image

人类分离的 2.3.4.4b 支系 A(H5N1)病毒在雪貂间的传播
自 2020 年以来,高致病性甲型禽流感(H5N1)在全球范围内前所未有地在野生鸟类种群中蔓延,并波及多种哺乳动物物种和零星人类1。2024 年 3 月,美国首次在奶牛中检测到 2.3.4.4b 支系甲型 H5N1 病毒,随后又在多个州检测到该病毒2 ,导致十多例人类确诊病例3,4。在本研究中,我们采用了雪貂模型来评估从得克萨斯州一名奶牛场工人身上分离出的 A/Texas/37/2024(TX/37)A(H5N1)病毒6。我们在此表明,该病毒在雪貂体内具有强大的全身感染能力,可导致高水平的病毒脱落并传播给新接触者。接种 TX/37 的雪貂会迅速出现严重的致命感染,其特征是病毒血症和肺外传播。病毒可在直接接触环境中有效传播,也可通过粪便间接传播。受感染动物向空气中散播的传染性病毒也证实了空气传播的可能性,尽管与高传播性的人类季节性毒株和猪源 H1 亚型毒株相比,其传播水平较低。我们的研究结果表明,尽管 TX/37 保持了类似禽类受体结合的特异性,但与 2024 年牛疫情爆发前分离出的其他 2.3.4.4b 支系病毒相比,TX/37 显示出更强的毒力、传播性和空气中的脱落性7 ,这强调了继续保持公共卫生警惕的必要性。
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来源期刊
Nature
Nature 综合性期刊-综合性期刊
CiteScore
90.00
自引率
1.20%
发文量
3652
审稿时长
3 months
期刊介绍: Nature is a prestigious international journal that publishes peer-reviewed research in various scientific and technological fields. The selection of articles is based on criteria such as originality, importance, interdisciplinary relevance, timeliness, accessibility, elegance, and surprising conclusions. In addition to showcasing significant scientific advances, Nature delivers rapid, authoritative, insightful news, and interpretation of current and upcoming trends impacting science, scientists, and the broader public. The journal serves a dual purpose: firstly, to promptly share noteworthy scientific advances and foster discussions among scientists, and secondly, to ensure the swift dissemination of scientific results globally, emphasizing their significance for knowledge, culture, and daily life.
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