Hematology-centered homeostatic immunity confers durable resistance to rock bream iridovirus (RBIV) in rock bream (Oplegnathus fasciatus)

This study demonstrates that rock bream ( Oplegnathus fasciatus ) surviving initial infection with rock bream iridovirus (RBIV) acquire a durable antiviral resistance mediated by a state of homeostatic immunity, characterized by hematological and physiological equilibrium rather than persistent immune activation. Following immunization with an experimental RBIV vaccine, fish were challenged intraperitoneally with 10 4 MCP copies/100 μL/fish of RBIV. Approximately 40 % succumbed within 20 days, whereas the remaining 60 % (n = 18) survived and were maintained for long-term observation. Secondary (100 dpi) and tertiary (370 dpi) challenges with a higher viral dose (10 7 MCP copies/100 μL/fish) resulted in complete survival, with all survivors maintaining viral loads below 10 3 MCP copies/mg throughout the 40 day post infection period. In contrast, naïve infected fish exhibited exponential viral amplification exceeding 10 6 MCP copies/mg by 15 days and 100 % mortality. Hematological and cytological analyses revealed that survivors maintained stable leukocyte and erythrocyte indices and normal cell morphology, while naïve fish exhibited leukocytic hyperactivation, anemia, and cytopathic mononuclear cells. Biochemical indicators, including glucose, total cholesterol, and triglycerides, also remained constant in survivors but decreased sharply in naïve fish, accompanied by elevated ALP activity indicating hepatic stress. Collectively, these findings indicate that RBIV survivors achieve long-term antiviral protection through blood-based physiological homeostasis, representing a functionally silent, hematology-centered immunity that prevents viral reactivation without sustained immune stimulation.