Infectious Bronchitis Virus Infection Induces Ferroptosis-Associated Changes with Lipid Peroxidation Dysregulation and Modulates Viral Replication

Abstract

Infectious bronchitis virus (IBV) causes significant disease in poultry; however, whether ferroptosis-associated responses are involved in IBV-induced cellular injury remains unclear. In this study, we examined ferroptosis-associated changes in the HD11 chicken macrophage cell line following IBV infection. IBV infection reduced cell viability, increased lactate dehydrogenase release, caused mitochondrial ultrastructural alterations, enhanced lipid peroxidation, depleted glutathione, increased intracellular ferrous iron, and altered the expression of ferroptosis-related genes. Treatment with ferrostatin-1 attenuated these changes and was accompanied by reduced viral replication. By contrast, ultraviolet-inactivated IBV did not induce comparable ferroptosis-associated changes, supporting an association between active IBV infection and these responses. Expression of the IBV nucleocapsid protein alone partially reproduced several ferroptosis-associated changes in HD11 cells. Epigallocatechin gallate reduced IBV-induced cellular injury and ferroptosis-associated changes, whereas RSL3 partly reversed its protective effect. Taken together, these results indicate that IBV infection induces ferroptosis-associated changes in chicken macrophages in association with increased lipid peroxidation, while Fer-1 treatment was accompanied by reduced viral replication. These findings support the involvement of ferroptosis-associated responses in IBV-host cell interactions.