The mitochondrial protein Cox17 negatively regulates antibacterial and antiviral defense in teleosts

Infections caused by pathogenic bacteria and viruses in economically important teleost species lead to substantial economic losses in China's aquaculture industry each year. Thus, the development of disease-resistant fish strains is an urgent priority in China, and translating technologies from model fish species to aquaculture species will facilitate this process. In this study, we found that zebrafish cox17 −/− and common carp CCcox17 +/− both conferred a strong dual resistance to both bacteria and virus infection. Mechanistically, cox17 deficiency increased the abundance of neutrophils and macrophages and upregulated the expression of Rad5, Rad7, Lamp1, and Ctsb, which play pivotal roles in phagolysosome formation and function. These changes also promoted acidification, ROS production, and the release of immune signals in these cells. Consequently, these cells exhibited enhanced migration in response to pathogen infection. Moreover, cox17 deficiency increased interferon (IFN) signaling and enhanced resistance to viral infection. This study provides insights into the development and breeding of disease-resistant fish for aquaculture.