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Infection of Zebrafish Embryos with Intracellular Bacterial Pathogens
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Transcriptional profiling of zebrafish intestines identifies macrophages as host cells for human norovirus infection

Emma Roux1, Reegan J Willms2, Jana Van Dycke1

  • 1Department of Microbiology, Immunology and Transplantation, Rega Institute, Virus-Host Interactions & Therapeutic Approaches (VITA) Research Group, KU Leuven, Leuven, Belgium.

Gut Microbes
|November 25, 2024
PubMed

Insights

Human noroviruses (HuNoVs) infect inflammatory macrophages in the zebrafish intestine, challenging the focus on epithelial cells. This discovery redefines the understanding of norovirus pathogenesis and control strategies.

Area of Science:

  • Virology
  • Immunology
  • Gastroenterology

Background:

  • Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis.
  • The precise cellular targets and tropism of HuNoVs within the host remain incompletely understood.
  • Previous research primarily focused on the intestinal epithelium, overlooking other potential host cells.

Purpose of the Study:

  • To investigate the cellular tropism of HuNoVs within the host.
  • To determine if macrophages serve as host cells for HuNoV replication.
  • To explore the role of macrophages in HuNoV infection dynamics.

Main Methods:

  • Utilized a zebrafish larval model for HuNoV infection studies.
  • Employed single-cell RNA sequencing (scRNA-seq) to identify host cells.
  • Applied fluorescence-activated cell sorting (FACS) and flow cytometry for cellular analysis.
  • Performed immunofluorescence to detect viral components within host cells.

Main Results:

  • Unbiased scRNA-seq identified macrophages as host cells for HuNoV replication.
  • HuNoV preferentially infected actively phagocytosing inflammatory macrophages.
  • Viral RNA and proteins were detected within intestinal macrophages, confirming replication.
  • Macrophages constituted approximately 23% of the identified HuNoV host cells.

Conclusions:

  • Macrophages, particularly inflammatory subtypes, are significant host cells for HuNoV replication.
  • This finding necessitates a reevaluation of the role of macrophages in HuNoV pathogenesis.
  • Identifies novel avenues for developing strategies to control norovirus infections.
Keywords:
Human noroviruscellular tropismhost cell identificationhost-virus interactionintestinal epitheliummacrophageszebrafish larval model

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