Division of Influenza Viruses and Other Respiratory Viruses, National Reference Centre for Influenza, Robert Koch-Institute, Seestrasse 10, Berlin 13353, Germany.
Division of Influenza Viruses and Other Respiratory Viruses, National Reference Centre for Influenza, Robert Koch-Institute, Seestrasse 10, Berlin 13353, Germany.
Int J Med Microbiol. 2024 Mar;314:151609. doi: 10.1016/j.ijmm.2024.151609. Epub 2024 Jan 24.
Interspecies transmission of influenza A viruses (IAV) from pigs to humans is a concerning event as porcine IAV represent a reservoir of potentially pandemic IAV. We conducted a comprehensive analysis of two porcine A(H1N1)v viruses isolated from human cases by evaluating their genetic, antigenic and virological characteristics. The HA genes of those human isolates belonged to clades 1C.2.1 and 1C.2.2, respectively, of the A(H1N1) Eurasian avian-like swine influenza lineage. Antigenic profiling revealed substantial cross-reactivity between the two zoonotic H1N1 viruses and human A(H1N1)pdm09 virus and some swine viruses, but did not reveal cross-reactivity to H1N2 and earlier human seasonal A(H1N1) viruses. The solid-phase direct receptor binding assay analysis of both A(H1N1)v showed a predominant binding to α2-6-sialylated glycans similar to human-adapted IAV. Investigation of the replicative potential revealed that both A(H1N1)v viruses grow in human bronchial epithelial cells to similar high titers as the human A(H1N1)pdm09 virus. Cytokine induction was studied in human alveolar epithelial cells A549 and showed that both swine viruses isolated from human cases induced higher amounts of type I and type III IFN, as well as IL6 compared to a seasonal A(H1N1) or a A(H1N1)pdm09 virus. In summary, we demonstrate a remarkable adaptation of both zoonotic viruses to propagate in human cells. Our data emphasize the needs for continuous monitoring of people and regions at increased risk of such trans-species transmissions, as well as systematic studies to quantify the frequency of these events and to identify viral molecular determinants enhancing the zoonotic potential of porcine IAV.
甲型流感病毒（IAV）在猪与人之间的种间传播是一个令人关注的问题，因为猪源 IAV 代表了潜在大流行 IAV 的储存库。我们通过评估两种从人类病例中分离出的猪源 A(H1N1)v 病毒的遗传、抗原和病毒学特征，对其进行了全面分析。这些人类分离株的 HA 基因分别属于欧亚类禽源猪源 A(H1N1)流感谱系的 1C.2.1 和 1C.2.2 分支。抗原分析显示，两种人畜共患的 H1N1 病毒与人类 A(H1N1)pdm09 病毒和一些猪源病毒之间存在显著的交叉反应性，但与 H1N2 和早期的人类季节性 A(H1N1)病毒没有交叉反应性。两种 A(H1N1)v 的固相直接受体结合分析均显示主要与类似于人类适应的 IAV 的α2-6-唾液酸化聚糖结合。对复制潜能的研究表明，两种 A(H1N1)v 病毒均能在人支气管上皮细胞中生长，其滴度与人类 A(H1N1)pdm09 病毒相似。在人肺泡上皮细胞 A549 中研究细胞因子诱导情况表明，两种从人类病例中分离出的猪源病毒诱导产生了更高水平的 I 型和 III 型 IFN 以及 IL6，与季节性 A(H1N1)或 A(H1N1)pdm09 病毒相比。综上所述，我们证明了两种人畜共患病毒在人细胞中显著的适应性。我们的数据强调需要对处于此类跨种传播风险增加的人群和地区进行持续监测，以及系统研究以量化这些事件的频率，并鉴定增强猪源 IAV 人畜共患潜力的病毒分子决定因素。
