Environmental-Nitrite-Enhanced Cyprinid Herpesvirus 2 Infection in Crucian Carp

The deterioration of water quality is associated with an increased disease risk, although the exact mechanism remains unclear. This study investigated the infection dynamics of cyprinid herpesvirus 2 (CyHV-2) in crucian carp (<i>Carassius auratus gibelio</i>) subjected to varying nitrite stress levels. A control group and three CyHV-2-infected groups exposed to nitrite concentrations of 0, 5, and 10 mg/L were set up. Results indicated that nitrite exposure caused a dose-dependent reduction in survival rates and decreased viral loads in the spleens of surviving fish. Nitrite stress elevated malondialdehyde (MDA) levels and glutathione peroxidase (GPx) activity, while reducing superoxide dismutase (SOD) and catalase (CAT) activities in the liver. Hepatic cytokine analysis revealed early peaks in tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β), alongside delayed response of interferon γ (IFN-γ) and interleukin 10 (IL-10), indicating impaired anti-inflammatory regulation. In the kidney, nitrite stress amplified immune gene expression, characterized by the upregulation of <i>tlr5</i> (<i>Toll-like receptor 5</i>) and <i>nf-</i><i>κb</i> (<i>nuclear factor κB</i>) and the inhibition of <i>iκκβ</i> (<i>inhibitor of NF-κB kinase subunit β</i>), leading to prolonged NF-κB signaling. This was associated with a marked upregulation of <i>il-1β</i> and <i>il-8</i> (<i>interleukin 8</i>), alongside a delayed <i>ifn-γ</i> response. The combination of nitrite stress and CyHV-2 infection exacerbated oxidative damage and triggered a maladaptive immune response, thereby accelerating disease progression.