Metabolic reprogramming links resident immunity and apoptosis in the liver of a primitive vertebrate model during viral infection

Background & Aims: Hepatitis induced by hepatitis B virus (HBV) infection significantly affected global public health, and illustrating the metabolic changes of hepatocytes during viral infection is important for clinical therapy. The present study adopted the rainbow trout liver research model to identify metabolic reprogramming during the resident immune responses and apoptosis in liver during viral infection.Approach & Results: We infected with rainbow trout with infectious haematopoietic necrosis virus (IHNV) via immersion and found histopathological changes in liver. Furthermore, TUNEL assay and RT-qPR results identified the elicited intrahepatic apoptosis during viral infection. Transcriptomic sequencing indicated that trout liver exhibited strong anti-viral immune responses along with inflammatory responses against viral infection. Combined omic analysis confirmed the metabolic programming with a shift from tricarboxylic acid cycle to pentose phosphate pathway and phospholipid synthesis pathway during viral infection. With prolonged infection period, intrahepatic T cells in survivor rainbow trout mediated resident adaptive immunity in liver to eliminate the evaded virus, during which process metabolic pathways recovered to perform formal functions along with the alleviated apoptosis.Conclusions: Our study illustrated the immuno-protective roles of resident immune cells including T cells in liver against viral infection induced apoptosis in a primitive vertebrate. More importantly, viral infected and survivor rainbow trout liver experienced metabolic programming including glucose utilization, phospholipid metabolism and amino acid metabolism, which not only support the nutritional immunoprevention strategy in aquaculture but also provide a reference for human clinical virus cases.