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Dissection of key factors correlating with H5N1 avian influenza virus driven inflammatory lung injury of chicken identified by single-cell analysis

文献类型： 外文期刊

作者： Dai, Manman 1 ; Zhu, Sufang 1 ; An, Zhihao 1 ; You, Bowen 1 ; Li, Ziwei 1 ; Yao, Yongxiu 2 ; Nair, Venugopal 2 ; Liao, Ming 1 ;

作者机构： 1.South China Agr Univ, Coll Vet Med, Natl & Reg Joint Engn Lab Medicament Zoonosis Prev, Guangdong Prov Key Lab Zoonosis Prevent & Control, Guangzhou, Peoples R China

2.Pirbright Inst, UK China Ctr Excellence Res Avian Dis, Pirbright, Surrey, England

3.UK China Ctr Excellence Res Avian Dis, Ash Rd, Guildford, Surrey, England

4.Univ Oxford, Oxford, England

5.Guangdong Acad Agr Sci, Inst Anim Hlth, Guangzhou, Peoples R China

期刊名称：PLOS PATHOGENS （ 影响因子：6.7； 五年影响因子：6.7 ）

ISSN： 1553-7366

年卷期： 2023 年 19 卷 10 期

页码：

收录情况： SCI

摘要： 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-beta, IL1 beta, 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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