Emerg Infect Dis. 2021 Oct;27(10):2619-2627. doi: 10.3201/eid2710.210297.
The numerous global outbreaks and continuous reassortments of highly pathogenic avian influenza (HPAI) A(H5N6/H5N8) clade 2.3.4.4 viruses in birds pose a major risk to the public health. We investigated the tropism and innate host responses of 5 recent HPAI A(H5N6/H5N8) avian isolates of clades 2.3.4.4b, e, and h in human airway organoids and primary human alveolar epithelial cells. The HPAI A(H5N6/H5N8) avian isolates replicated productively but with lower competence than the influenza A(H1N1)pdm09, HPAI A(H5N1), and HPAI A(H5N6) isolates from humans in both or either models. They showed differential cellular tropism in human airway organoids; some infected all 4 major epithelial cell types: ciliated cells, club cells, goblet cells, and basal cells. Our results suggest zoonotic potential but low transmissibility of the HPAI A(H5N6/H5N8) avian isolates among humans. These viruses induced low levels of proinflammatory cytokines/chemokines, which are unlikely to contribute to the pathogenesis of severe disease.
大量的高致病性禽流感（HPAI）A（H5N6/H5N8）2.3.4.4 分支病毒在鸟类中的全球暴发和持续重组，对公共卫生构成了重大威胁。我们研究了 5 种最近的 HPAI A（H5N6/H5N8）禽源性 2.3.4.4b、e 和 h 分支病毒在人呼吸道类器官和原代人肺泡上皮细胞中的嗜性和先天宿主反应。HPAI A（H5N6/H5N8）禽源性分离株在这两种模型或任一种模型中均能有效复制，但复制能力低于流感 A（H1N1）pdm09、HPAI A（H5N1）和 HPAI A（H5N6）的人类分离株。它们在人呼吸道类器官中显示出不同的细胞嗜性；有些可感染所有 4 种主要的上皮细胞类型：纤毛细胞、分泌细胞、杯状细胞和基底细胞。我们的研究结果表明，HPAI A（H5N6/H5N8）禽源性分离株在人类中具有潜在的人畜共患病，但传播能力较低。这些病毒诱导低水平的促炎细胞因子/趋化因子，不太可能导致严重疾病的发病机制。
