Transcriptional landscape of the kidney in chickens infected by virulent or avirulent infectious bronchitis virus.

Abstract

Infectious Bronchitis Virus (IBV), a γ-coronavirus, is responsible for respiratory disease, renal injury, and reproductive disorders in poultry. This study presents a comparative transcriptomic profiling of chicken kidney infected with either the virulent GD17/04 strain or the attenuated 4/91 vaccine strain of IBV. RNA sequencing and functional enrichment analyses revealed that both strains initially activate antiviral sensing pathways. However, the virulent strain subsequently provoked sustained and amplified immune activation, involving NF-κB signaling, Jak-STAT signaling, and adaptive immune responses, culminating in severe renal dysregulation. In contrast, infection with the vaccine strain elicited a tempered immune response, accompanied by enhanced metabolic homeostasis and tissue repair processes. Through WGCNA, we identified a virulence-specific immune module (turquoise) and a renal development-associated module (yellow) linked to virus-induced nephropathy for GD17/04, alongside a balanced immune regulatory module (brown) for the 4/91 strain. Intersection analysis further revealed that the virulent strain induced a broader spectrum of immune activation, whereas the vaccine elicited a more restrained response, largely encompassed within that of the virulent infection-including shared pathways such as NOD-like receptor signaling. Among 69 core genes commonly upregulated in a virulence- and time-dependent manner by both strains, protein-protein interaction analysis identified RSAD2, ZNFX1, and TRIM25 as central hub genes. Functional investigations established TRIM25 as a pro-viral host factor: its knockdown significantly suppressed viral replication, whereas its overexpression exacerbated viral propagation. This work provides the first WGCNA-based transcriptional landscape of renal infection by IBV, elucidating virulence-dependent immune signatures and underscoring the pivotal role of TRIM25 in viral pathogenesis.