Integrated Transcriptome–Translatome Analysis Reveals Translational Buffering in the Liver of Chickens Infected with Fowl Adenovirus Serotype 4 Strain GXYL-03, a Strain with Reduced Virulence

Abstract

Fowl adenovirus serotype 4 (FAdV-4) causes hydropericardium-hepatitis syndrome (HHS) and has resulted in severe economic losses to the poultry industry in China since 2015. In this study, we isolated a naturally occurring strain with reduced virulence designated GXYL-03, which caused no gross or histological HHS lesions in 4-week-old specific pathogen-free (SPF) chickens infected at 106 TCID50, whereas clinical signs and partial mortality were observed at higher doses of 107–108 TCID50. After a single immunization with 5 × 104 TCID50 of GXYL-03, all ten immunized SPF chickens survived throughout the 14-day observation following lethal GX2017-005 challenge, whereas all ten challenge-control chickens died. Integrated transcriptome and translatome analyses were performed on the livers of chickens infected with FAdV-4 strains of differing virulence by RNA sequencing (RNA-seq) and polysome profiling, with three biological replicates per group. The polysome/non-polysome (P/NP) ratio did not differ significantly among groups (p > 0.05), indicating stable global translation flux. The GXYL-03 group had 2,131 transcriptomic differentially expressed genes (DEGs) but only 71 translatomic DEGs; the GX2017-005 group had 7767 and 148, respectively, indicating that only 3.3% and 1.9% of transcriptional perturbations were transmitted to translation, revealing a pronounced translational buffering effect. Translation efficiency (TE) changes were predominantly suppressive, and downregulated genes accounted for 58.6% and 61.8% of TE changes in the two strains. The functional enrichment of genes whose expression was synchronously upregulated at both levels (TE+RNA+) revealed that GXYL-03 was enriched mainly in protein-coding genes involved in cellular stress, DNA damage repair, vesicle transport, and protein homeostasis (HSPA2, HSPB9, FANCD2, EHD2, and Vault), whereas GX2017-005 was enriched in liver injury-related genes (CD74, ATG2B, FKBP5, ND1, and COX1) that were not differentially expressed in GXYL-03. This study provides insights into the development of FAdV-4 strains with reduced virulence and virus–host interactions.