Multi-tissue transcriptomics reveals age-dependent susceptibility to grass carp reovirus linked to metabolic...

Grass carp (Ctenopharyngodon idella) is an important freshwater aquaculture species. Infection by grass carp reovirus (GCRV) can cause hemorrhagic disease and lead to major economic losses in aquaculture. Susceptibility to GCRV is strongly age dependent: juveniles (≤1 year old) are highly vulnerable, whereas fish aged three years or older show much greater tolerance. In this study, transcriptome sequencing was used to compare gene expression in the gill, intestine, head kidney, muscle, and spleen of three-year-old and six-month-old grass carp at pre-infection (Day 0) and at Days 4 and 7 post-infection. The results showed that GCRV induced a strong acute immune and inflammatory response in six-month-old fish, while three-year-old fish mounted a more moderate and controlled response. Further analysis suggested that sterol metabolism, lipid metabolism, and oxidative stress were closely linked to the excessive inflammation and cytokine surge observed in younger fish during the later stage of infection (Days 4-7). To better understand the mechanisms underlying hemorrhagic disease, we also examined changes in extracellular matrix (ECM) and cell junction-related pathways during this late phase and integrated these findings with the acute inflammatory response in juveniles. Overall, our results reveal clear age-related differences in the immune and metabolic responses to GCRV infection. These findings highlight the importance of the metabolism - immune axis and tissue barrier integrity in determining susceptibility in juvenile grass carp. This study provides new insight into the molecular basis of age-dependent resistance to GCRV infection.