Dissection of key factors correlating with H5N1 avian influenza virus driven inflammatory lung injury of chicken identified by single-cell analysis.
Dissection of key factors correlating with H5N1 avian influenza virus driven inflammatory lung injury of chicken identified by single-cell analysis.
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与H5N1禽流感病毒相关的关键因素的解剖学因单细胞分析鉴定出的鸡的炎症肺损伤。
DOI：
10.1371/journal.ppat.1011685
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发表时间：
2023-10
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
鸡肺是禽流感病毒（AIV）感染的重要靶器官，不同的致病性病毒株导致不同的预后。采用单细胞RNA测序（scRNA-seq）技术，对H5 N1高致病性禽流感病毒（HPAIV）和H9 N2低致病性禽流感病毒（LPAIV）感染的鸡肺组织中16种细胞（19个簇）的转录组进行了系统、连续的分析。值得注意的是，我们为这些细胞类型开发了一个有价值的标记基因目录。与H9 N2感染相比，H5 N1感染可同时诱导广泛的病毒复制和多种细胞类型的免疫反应。更重要的是，我们提出，具有大量病毒复制、促炎细胞因子（IFN-β、IL 1 β、IL 6和IL 8）的浸润性炎性巨噬细胞（簇0、1和14），以及通过CCL 4、CCL 19和CXCL 13的各种细胞群的新兴相互作用，可能促成H5 N1 AIV驱动的炎性肺损伤。我们的数据揭示了H5 N1和H9 N2 AIV感染后鸡肺组织中复杂但不同的免疫反应景观，并破译了AIV驱动鸡炎症反应的潜在机制。此外，这篇文章提供了一个丰富的数据库，为不同类型的细胞对AIV感染的反应的分子基础。低致病性禽流感病毒（LPAIV）H9 N2和高致病性禽流感病毒（HPAIV）H5 N1是禽流感的主要流行亚型，给家禽造成了巨大的经济损失，也对人类造成了潜在的威胁。因此，深入研究禽流感病毒的致病机理，对开发有效的防控方法是十分必要的。在我们的研究中，使用鸡肺中16种细胞类型的单细胞RNA测序分析，我们揭示了H5 N1和H9 N2 AIV感染后复杂而独特的免疫反应景观，并确定了导致H5 N1 AIV驱动的炎性肺损伤的关键因素。因此，本研究为禽流感的防控提供了新的靶点和方向。
Chicken lung is an important target organ of avian influenza virus (AIV) infection, and different pathogenic virus strains lead to opposite prognosis. Using a single-cell RNA sequencing (scRNA-seq) assay, we systematically and sequentially analyzed the transcriptome of 16 cell types (19 clusters) in the lung tissue of chickens infected with H5N1 highly pathogenic avian influenza virus (HPAIV) and H9N2 low pathogenic avian influenza virus (LPAIV), respectively. Notably, we developed a valuable catalog of marker genes for these cell types. Compared to H9N2 AIV infection, H5N1 AIV infection induced extensive virus replication and the immune reaction across most cell types simultaneously. More importantly, we propose that infiltrating inflammatory macrophages (clusters 0, 1, and 14) with massive viral replication, pro-inflammatory cytokines (IFN-β, IL1β, IL6 and IL8), and emerging interaction of various cell populations through CCL4, CCL19 and CXCL13, potentially contributed to the H5N1 AIV driven inflammatory lung injury. Our data revealed complex but distinct immune response landscapes in the lung tissue of chickens after H5N1 and H9N2 AIV infection, and deciphered the potential mechanisms underlying AIV-driven inflammatory reactions in chicken. Furthermore, this article provides a rich database for the molecular basis of different cell-type responses to AIV infection. The low-pathogenicity avian influenza virus (LPAIV), H9N2, and highly pathogenic avian influenza virus (HPAIV), H5N1 are the main epidemic subtypes, resulting in great economic losses on poultry and potentially threat to human. Thus, in-depth exploration of AIV pathogenesis in chickens is necessary for developing efficient control methods. In our study, using a single-cell RNA sequencing analysis of 16 cell types in the chicken lung, we revealed complicated and distinct immune response landscapes after H5N1 and H9N2 AIV infection, and identified key factors contributing to H5N1 AIV driven inflammatory lung injury. Therefore, our study potentially provides new targets and direction for AIV control.
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