# Comparative analysis of ducks liver gene expressions infected with virulent or attenuated DHAV-3 reveals divergent host responses to viruses of different virulence

## TL;DR

This study compares how duck livers respond to a deadly and a weakened strain of DHAV-3, showing stronger immune reactions to the more harmful virus.

## Contribution

The study reveals distinct host gene expression patterns and immune responses to DHAV-3 strains of different virulence.

## Key findings

- The virulent DHAV-3 strain induced 2,355 DEGs, while the attenuated strain caused only 322 DEGs.
- Immune pathways like TLR and RLR were strongly activated by the virulent strain, leading to a robust IFN-I response.
- 77 immune-related genes were identified, with key genes validated through RT-qPCR and ELISA.

## Abstract

Duck hepatitis A virus type 3 (DHAV-3) causes acute fatal hepatitis in ducklings.

This study compared host transcriptomic responses in duck livers following infection with virulent (HB) or attenuated (HB80) strains.

RNA sequencing (RNA-Seq) revealed that the virulent HB strain induced 2,355 differentially expressed genes (DEGs) at 2 days post-infection (dpi), compared to only 322 DEGs triggered by the attenuated HB80 strain. Functional analysis showed that the HB strain robustly activated immune pathways, particularly Toll-like receptor (TLR) and RIG-I-like receptor (RLR) signaling, leading to a potent type I interferon (IFN-I) response and marked chemokine upregulation. In contrast, the HB80 strain elicited a markedly milder immune reaction. Among the DEGs, 77 immune-related genes were identified, with significant enrichment in the IFN-I signaling pathway, suggesting their critical role in initiating an interferon storm and subsequent chemokine upregulation. Selected key genes (IFN-α2, RSAD2, RIG-I, MDA5, TBK1, TLR7) were validated by RT-qPCR and ELISA for targeted protein confirmation.

These findings delineate divergent host transcriptomic responses to virulent vs. attenuated DHAV-3 and highlight IFN-I signaling as a central axis in antiviral immunity.