Abstract

Although Cyprinid herpesvirus 2 (CyHV-2, species Cyprinid herpesvirus 2) was identified as the causative agent of hemorrhagic disease of gills in gibel carp, opportunistic pathogens, including Aeromonas hydrophila, were found frequently in CyHV-2-infected fish. However, the pathogenicity and mechanism of viral and bacterial coinfection as well as the interaction between viral and bacterial pathogens remain unknown. In this study, epidemiological investigation and experimental infection suggested that CyHV-2 infection triggered secondary bacterial infections and that the outcome of a secondary infection was dependent on the time interval between viral and bacterial administration. Lethal synergy and antagonism of CyHV-2 and bacterial coinfection occurred in the group administrated A. hydrophila on day 3 and day 14 after CyHV-2 infection, respectively. The results of pathogen burden analysis demonstrated that the mortality of crucian carp coinfected with CyHV-2 and A. hydrophila in is dependent on pathogen burden. Evaluation of the integrity of the intestinal mucosal barrier and transcriptome analysis demonstrated the disruption of gut homeostasis after CyHV-2 infection in crucian carp. In total, these results imply that CyHV-2 infection disrupts the intestinal mucosal barrier and results in bacterial translocation, which contributes to the severe mortality of CyHV-2 infection.

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