Acipenserid Herpesvirus 2 (AciHV-2) is a double-stranded DNA virus in the family Alloherpesviridae that causes morbidity and mortality in white sturgeon (Acipenser transmontanus). As the primary source of caviar and sturgeon meat in the United States, losses of subadult white sturgeon due to AciHV-2 result in significant economic losses to the aquaculture industry and subsequently impact the communities that rely on this important agricultural practice. Despite the evidence that other members of the Alloherpesviridae family have shown latency capabilities and the current understanding that herpesviruses can impact the host’s immunocompetency long term, little is known about AciHV-2 and its interactions with the immune system of the white sturgeon. The work presented in this dissertation aims to further characterize AciHV-2 and provide insight into its impact on the immune system of the white sturgeon. The whole genome of AciHV-2 was assembled and described, and an initial prediction of immune-related host homologs was performed. A diagnostic quantitative polymerase chain reaction assay was developed for the detection of the terminase gene in skin tissue of white sturgeon. This assay had a 100% relative accuracy for the detection of AciHV-2 during an active outbreak when compared to viral culture. Co-infection challenges with Streptococcus iniae in a latency/persistent-infection model were performed and revealed that fish exposed to AciHV-2 experienced increased mortality during subsequent S. iniae outbreaks in a bacterial dose-dependent manner. In addition, the co-infected group was unable to mount strong humoral immunity, had decreased transcription of tumor necrosis factor alpha, and had decreased serotransferrin 2 protein levels. Finally, differential transcript analysis of the host in response to AciHV-2 in vitro at 10 days post-infection suggests that several immune-related pathways are regulated in a manner that may benefit viral infection. The contributions of this thesis work serve as a foundation for further host-microbe interaction studies as it pertains to AciHV-2 and the white sturgeon, and provide evidence of the need to consider the full history of the hatchery when designing preventative medicine strategies.