美国堪萨斯州立大学Juergen A. Richt和德国弗里德里希-洛夫勒研究所Martin Beer共同合作，近期取得重要工作进展。他们研究提出了实验感染的小牛和奶牛中H5N1分支2.3.4.4b的动态。相关研究成果2024年9月25日在线发表于《自然》杂志上。

据介绍，2024年3月，美国德克萨斯州首次报告了奶牛感染高致病性禽流感病毒（HPAIV）2.3.4.4b分支的H5N1病例。随后迅速传播到13个州的190多个农场。

研究人员提供了两项独立的2.3.4.4b分支实验感染研究的结果，这些研究评估了（i）小牛对美国H5N1牛分离基因型B3.13（H5N1 B3.13）的口鼻易感性和传播，以及（ii）哺乳奶牛在直接乳腺接种H5N1 B3.13或当前欧盟H5N1野鸟分离基因型euDG（H5N1 euDG）后的易感性。小牛接种疫苗后，其鼻腔复制和脱落程度适中，没有严重的临床症状或传播给哨兵小牛。

在奶牛中，感染没有导致鼻腔脱落，但两种H5N1分离株都观察到严重的急性乳腺感染，伴有坏死性乳腺炎和高烧。牛奶产量迅速大幅下降，奶牛的身体状况严重受损。牛奶中的病毒滴度迅速达到10⁸ TCID₅₀/mL的峰值，但并未引发全身感染。适应性突变PB2 E627K出现在H5N1 euDG的乳腺内复制后。

总之，这一研究表明，除了H5N1 B3.13，其他高致病性禽流感病毒H5N1毒株也有可能在奶牛的乳房中复制，牛奶和挤奶程序，而不是呼吸道传播，可能是H5N1在牛之间传播的主要途径。

附：英文原文

Title: H5N1 clade 2.3.4.4b dynamics in experimentally infected calves and cows

Author: Halwe, Nico Joel, Cool, Konner, Breithaupt, Angele, Schn, Jacob, Trujillo, Jessie D., Nooruzzaman, Mohammed, Kwon, Taeyong, Ahrens, Ann Kathrin, Britzke, Tobias, McDowell, Chester D., Piesche, Ronja, Singh, Gagandeep, Pinho dos Reis, Vinicius, Kafle, Sujan, Pohlmann, Anne, Gaudreault, Natasha N., Corleis, Bjrn, Ferreyra, Franco Matias, Carossino, Mariano, Balasuriya, Udeni B. R., Hensley, Lisa, Morozov, Igor, Covaleda, Lina M., Diel, Diego, Ulrich, Lorenz, Hoffmann, Donata, Beer, Martin, Richt, Juergen A.

Issue&Volume: 2024-09-25

Abstract: In March 2024, highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4b H5N1 infections in dairy cows were first reported from Texas, USA1. Rapid dissemination to more than 190 farms in 13 states followed2. Here, we provide results of two independent clade 2.3.4.4b experimental infection studies evaluating (i) oronasal susceptibility and transmission in calves to a US H5N1 bovine isolate genotype B3.13 (H5N1 B3.13) and (ii) susceptibility of lactating cows following direct mammary gland inoculation of either H5N1 B3.13 or a current EU H5N1 wild bird isolate genotype euDG (H5N1 euDG). Inoculation of the calves resulted in moderate nasal replication and shedding with no severe clinical signs or transmission to sentinel calves. In dairy cows, infection resulted in no nasal shedding, but severe acute mammary gland infection with necrotizing mastitis and high fever was observed for both H5N1 isolates. Milk production was rapidly and drastically reduced and the physical condition of the cows was severely compromised. Virus titers in milk rapidly peaked at 108 TCID50/mL, but systemic infection did not ensue. Notably, adaptive mutation PB2 E627K emerged after intramammary replication of H5N1 euDG. Our data suggest that in addition to H5N1 B3.13, other HPAIV H5N1 strains have the potential to replicate in the udder of cows and that milk and milking procedures, rather than respiratory spread, are likely the primary routes of H5N1 transmission between cattle.

DOI: 10.1038/s41586-024-08063-y

Source: https://www.nature.com/articles/s41586-024-08063-y