Ostreid Herpesvirus type 1 (OsHV-1) has become a serious infective agent of the Pacific oyster livestock worldwide. In particular, the OsHV-1 muVar subtype has been associated to severe mortality episodes concerning Crassostrea gigas in France and other regions of the world such as Australia and New Zealand. Factors triggering productive infections and virus interactions with susceptible and resistant bivalve hosts are not completely understood though some studies have been undertaken to explore the genes expressed in oysters after infection. We took advantage of an highly infected oyster sample to perform an in-vivo dual RNA-seq analysis. An extremely high sequencing coverage allowed us to explore in detail the Herpesvirus genome and transcriptome, and to identify viral-activated molecular pathways in Crassostrea gigas, thus expanding the current knowledge on the host-virus interactions.