Ostreid herpesvirus 1 (OsHV-1) is a major pathogen associated with summer mortality in bivalve mollusks, but the host-side determinants of susceptibility remain poorly characterized outside oysters. In this study, we compared the responses of Chinese (CS) and Korean (KS) populations of the ark clam Scapharca broughtonii to experimental OsHV-1 challenge. The results showed that OsHV-1 established a markedly strong infection in the CS population but not the KS population, as indicated by high viral DNA loads, severe tissue pathology, detection of viral particles by transmission electron microscopy, broad viral transcription, and substantially high mortality. To explore the molecular basis of this contrasting outcome, we further performed comparative transcriptomic and proteomic analyses. Transcriptomic analysis identified two membrane-associated genes, atrial natriuretic peptide receptor A (NPR-A) and tyrosine-protein kinase receptor (TYRO3-like), that were more highly expressed in the susceptible CS population, suggesting that early host–virus interaction may differ between populations as a result of differentially expressed membrane molecules. Proteomic analysis identified 94 differentially abundant proteins between CS and KS populations; notably, ferritin and superoxide dismutase (SOD) were highly expressed in the less susceptible KS population, leading to stronger basal antioxidant and stress-defense capacity. Taken together, these findings definitively confirmed the significant differential susceptibility to OsHV-1 infection between the two S. broughtonii geographic populations and revealed that this divergent phenotype might involve both population-biased expression of candidate membrane-associated factors and differences in defense-related protein abundance. This study provides candidate markers for future disease-resistance evaluation and breeding in ark clam and offers a basis for further investigation of population-level variation in bivalve–virus interactions.
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