Infection Dynamics of Cyprinid Herpesvirus 2 in the Disease-resistant Goldfish Strain after Experimental Infection

Abstract

A strain of Azumanishiki variety of goldfish Carassius auratus resistant to herpesvirus hematopoietic necrosis, caused by cyprinid herpesvirus 2 (CyHV-2), has been established. In this study, we investigated virus kinetics and histopathological changes in resistant Azumanishiki and susceptible goldfish after experimental infection via intraperitoneal (IP) injection or immersion. Following experimental challenge, the resistant strain exhibited low mortality even after IP injection with a virus dose 10,000-fold higher than the lethal dose for susceptible fish. In the immersion-challenged susceptible fish, the virus DNA loads reached over 10⁷ copies/mg of hematopoietic tissue at 5 days post-infection (dpi), whereas in the resistant fish, the virus DNA level peaked at approximately 5 dpi at less than 10⁶ DNA copies/mg. Histopathological analysis revealed a fundamental divergence in cellular responses: the susceptible fish exhibited characteristic infected cells with enlarged nuclei and chromatin marginalization, followed by diffuse necrosis in hematopoietic tissues. In contrast, the resistant strain showed only small infection foci with less pronounced nuclear enlargement, followed by marked leukocyte infiltration at the foci and subsequent tissue recovery, with no diffuse necrotic lesions observed. These findings suggest that both the suppression of virus replication and the subsequent immune response play a role in the mechanisms underlying CyHV-2 resistance.