Immune cell-resolved transcriptomics provides insights into the basis for variations of fish genetic resistance to viral disease

TL;DR

This study uses transcriptomics to explore how immune cells in fish respond differently to a virus, revealing genetic factors behind resistance and susceptibility.

Contribution

The study integrates bulk and single-cell RNA-seq to map immune cell-specific transcriptomic responses in fish with extreme resistance or susceptibility to a virus.

Findings

Resistant and susceptible fish showed distinct transcriptomic responses to VHSV, with resistant fish exhibiting broader immune gene activation.

Monocytic cells in resistant fish upregulated proinflammatory genes, while susceptible fish showed increased IFN-induced gene expression.

The study highlights a conserved core of interferon-stimulated genes and line-specific immune responses in vertebrates.

Abstract

The genetic basis of host resistance to viral infections is generally shaped by complex interactions between host genetic variations affecting antiviral immunity and the rapid evolutionary adaptability of viruses. In this study, we investigated two isogenic rainbow trout lines exhibiting extreme resistance or susceptibility to the rhabdovirus VHSV. We compared transcriptomes of the pronephros — a major lymphoid organ in fish — at steady state and following VHSV infection. By integrating bulk tissue RNA-seq with single-cell RNA-seq, we mapped the divergent transcriptomic responses of resistant and susceptible fish to specific immune cell types.

At steady state, differences in antiviral pathways were minimal. However, VHSV triggered markedly distinct transcriptomic shifts between the lines. Both resistant and susceptible fish exhibited a broad transcriptional response enriched in core type I interferon (IFN) pathway genes. However, line-specific responses were enriched in genes induced by infection independently of type I IFN. In resistant fish, lymphocyte responses included type I IFN pathway, numerous transcription factors, and various cytokine receptors. In contrast, lymphocyte responses in susceptible fish involved only a limited set of type I IFN-induced genes. Monocytic cell responses also diverged: susceptible fish upregulated IFN-induced genes, while resistant fish showed increased expression of proinflammatory genes.

This study reveals the contribution of the core set of interferon-stimulated genes conserved across vertebrates to the response of different immune cells and the response of other genes in resistant and susceptible fish. It provides a comprehensive basis for evolutionary studies of resistance to viruses in vertebrates.

The online version contains supplementary material available at 10.1186/s12915-025-02452-z.

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