Hematology-centered analysis shows stage-dependent systemic responses during lymphocystis disease virus (LCDV)...

Lymphocystis disease virus (LCDV) infection in olive flounder has traditionally been considered a chronic condition with limited systemic involvement; however, its temporal and systemic progression remains poorly defined. In this study, viral kinetics were integrated with hematological, biochemical, cytological, and transcriptional analyses to characterize infection dynamics following intramuscular challenge. Viral loads in muscle peaked at approximately 10⁷ copies/mg at 25 dpi, whereas visible lesions emerged only at 35 dpi, suggesting a temporal difference between internal viral replication and external clinical manifestation. Hematological alterations occurred rapidly, with leukocyte suppression evident at 4 dpi (lymphocytes decreased by over 50% and monocytes by over 95%), followed by sustained reductions in erythrocyte indices (approximately 36% in red blood cell (RBC) and 40% in hemoglobin). Biochemical profiles exhibited stage-dependent variation, with intermediate stages (7-15 dpi) forming a cluster characterized by decreased glucose levels (approximately 48%) and marked increases in lipid-related parameters (greater than 100%). Multivariate analyses further indicated stage-dependent clustering patterns in systemic responses. Transcriptional responses were tissue-specific, with pronounced late-stage upregulation in the kidney (HBA1 approximately 76-fold; STAT3 > 400-fold, reaching up to approximately 1400-fold), whereas responses in muscle were comparatively limited. Collectively, these findings suggest that LCDV infection is associated with coordinated changes across hematological, metabolic, and transcriptional parameters. Blood-based parameters may provide useful indicators of subclinical infection and infection progression.