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

## TL;DR

This study shows that environmental nitrite stress worsens viral infections in crucian carp by causing oxidative damage and disrupting immune responses.

## Contribution

The study reveals how nitrite stress enhances Cyprinid Herpesvirus 2 infection through oxidative and immune mechanisms in crucian carp.

## Key findings

- Nitrite exposure caused dose-dependent survival rate decreases in crucian carp.
- Nitrite stress disrupted redox homeostasis and triggered maladaptive immune responses.
- Nitrite stress and CyHV-2 infection together accelerated disease progression in crucian carp.

## Abstract

Intensified pond aquaculture leads to a deterioration in water quality, often leading to disease outbreaks. Although it is well established that poor water quality exacerbates disease risk, the mechanisms by which environmental stress contributes to disease outbreaks remain unclear. This study investigated viral infections in crucian carp (Carassius auratus gibelio) exposed to nitrite stress. The findings indicated that nitrite exposure caused a dose-dependent decrease in survival rates. This effect may be attributed to nitrite-stress-enhancing, virus-induced hepatic lipid peroxidation, caused premature hyperinflammatory responses, and disrupting anti-inflammatory regulation. In summary, environmental nitrite stress enhanced viral infections by enhancing oxidative damage, disrupting redox homeostasis, and triggering maladaptive immune responses, thereby accelerating disease progression.

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 (Carassius auratus gibelio) 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 tlr5 (Toll-like receptor 5) and nf-κb (nuclear factor κB) and the inhibition of iκκβ (inhibitor of NF-κB kinase subunit β), leading to prolonged NF-κB signaling. This was associated with a marked upregulation of il-1β and il-8 (interleukin 8), alongside a delayed ifn-γ response. The combination of nitrite stress and CyHV-2 infection exacerbated oxidative damage and triggered a maladaptive immune response, thereby accelerating disease progression.