The herpesviral haematopoietic necrosis with acute gill hemorrhage has recently become prevalent in gibel carp farming regions and has resulted in significant losses. Although several herpesvirus strains (belonging to Cyvirus cyprinidallo2 ) have been isolated, the permissive cells in vivo , how the virus manipulates host cell processes, and causes disease remain largely unclear. In this study, the isolate Carassius auratus herpesvirus (CaHV) was used as a model to dissect the interactions between virus and host through single-cell RNA sequencing (scRNA-seq) and functional validation. Spleen of the infected fish was selected for scRNA-seq analysis for its highest viral load, which resolved splenic cells into ten distinct clusters, and macrophages and mural cells were identified as the major viral permissive cells. By classification of the permissive cells into infected and bystander cells, we found that CaHV induced widespread suppression of host cellular processes in infected cells, especially the antiviral responses. Meanwhile, negative immune regulators and factors potentially involved in viral entry, assembly, and egress, including heparan sulfate and the ESCRT complex, were upregulated to facilitate virus infection. Further sub-clustering and pseudotime inference analysis revealed distinct macrophage subpopulations, while novel subsets emerged with CaHV infection. Macrophage subsets toward M2-like polarization were also observed. In addition, enrichment and apoptosis analyses revealed that the hemorrhagic symptoms in diseased fish resulted from a combination of virus-induced coagulation dysfunction and endothelial cell programmed cell death. Collectively, the present study provides comprehensive new insights into the targeted cells of Cyvirus cyprinidallo2 and its interactions with the host, while also identifying potential targets for disease control.
Ke et al. (2026) studied this question.