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

PLoS Pathog. 2023 Oct 11;19(10):e1011685. doi: 10.1371/journal.ppat.1011685. eCollection 2023 Oct.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chickens / metabolism
  • Influenza A Virus, H5N1 Subtype* / genetics
  • Influenza A Virus, H9N2 Subtype* / genetics
  • Influenza in Birds*
  • Lung Injury*
  • Single-Cell Analysis

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (31830097 to ML); National Natural Science Foundation of China (32211530072 to MD); National Key R&D Program of China (2022YFD1801005 to MD); the National Natural Science Foundation of Guangdong Province (2022A1515012480 to MD); Science and Technology Plan Project of Guangzhou City (202201010512 to MD); Young Elite Scientists Sponsorship Program by CAST (2020QNRC001 to MD); Biotechnology and Biological Sciences Research Council (BBSRC) Newton Fund Joint Centre Awards on “UK-China Centre of Excellence for Research on Avian Diseases” (BBS/OS/NW/000007 to VN). Special fund for scientific innovation strategy-construction of high-level Academy of Agriculture Science-Distinguished Scholar (R2020PY-JC001 and 202110TD to ML). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.