Deciphering infected cell types, hub gene networks and cell-cell communication in infectious bronchitis virus via single-cell RNA sequencing

PLoS Pathog. 2024 May 14;20(5):e1012232. doi: 10.1371/journal.ppat.1012232. eCollection 2024 May.

Abstract

Infectious bronchitis virus (IBV) is a coronavirus that infects chickens, which exhibits a broad tropism for epithelial cells, infecting the tracheal mucosal epithelium, intestinal mucosal epithelium, and renal tubular epithelial cells. Utilizing single-cell RNA sequencing (scRNA-seq), we systematically examined cells in renal, bursal, and tracheal tissues following IBV infection and identified tissue-specific molecular markers expressed in distinct cell types. We evaluated the expression of viral RNA in diverse cellular populations and subsequently ascertained that distal tubules and collecting ducts within the kidney, bursal mucosal epithelial cells, and follicle-associated epithelial cells exhibit susceptibility to IBV infection through immunofluorescence. Furthermore, our findings revealed an upregulation in the transcription of proinflammatory cytokines IL18 and IL1B in renal macrophages as well as increased expression of apoptosis-related gene STAT in distal tubules and collecting duct cells upon IBV infection leading to renal damage. Cell-to-cell communication unveiled potential interactions between diverse cell types, as well as upregulated signaling pathways and key sender-receiver cell populations after IBV infection. Integrating single-cell data from all tissues, we applied weighted gene co-expression network analysis (WGCNA) to identify gene modules that are specifically expressed in different cell populations. Based on the WGCNA results, we identified seven immune-related gene modules and determined the differential expression pattern of module genes, as well as the hub genes within these modules. Our comprehensive data provides valuable insights into the pathogenesis of IBV as well as avian antiviral immunology.

MeSH terms

  • Animals
  • Cell Communication*
  • Chickens*
  • Coronavirus Infections* / genetics
  • Coronavirus Infections* / virology
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology
  • Gene Regulatory Networks*
  • Infectious bronchitis virus* / genetics
  • Infectious bronchitis virus* / physiology
  • Poultry Diseases / genetics
  • Poultry Diseases / immunology
  • Poultry Diseases / virology
  • Sequence Analysis, RNA
  • Single-Cell Analysis*

Grants and funding

This study was supported by the National Key Research and Development Program of China (2021YFD1801103) and the 2115 Talent Development Program of China Agricultural University to GZ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.