Reactive oxidative species (ROS) are important inflammatory mediators. Electrons escaping from the mitochondrial electron transport chain (ETC) during oxidative phosphorylation (OXPHOS) in the mitochondrial respiratory chain (RC) complexes contribute to ROS production. The cellular
antioxidant enzymes are important for maintaining ROS release at the physiological levels. It has been reported that BoHV-1
infection induces overproduction of ROS and oxidative
mitochondrial dysfunction in cell cultures. In this study, we found that chemical interruption of RC complexes by TTFA (an inhibitor of RC complex II),
NaN3 (an inhibitor of RC complex IV), and
oligomycin A (an inhibitor of
ATP synthase) consistently decreased virus productive
infection, suggesting that the integral processes of RC complexes are important for the virus replication. The
virus infection significantly increased the expression of subunit SDHB (
succinate dehydrogenase) and MTCO1 (
cytochrome c oxidase subunit I), critical components of RC complexes II and IV, respectively. The expression of
antioxidant enzymes including
superoxide dismutase 1 (SOD1), SOD2,
catalase (CAT), and
glutathione peroxidase 4 (GPX4) was differentially affected following the
virus infection. The
protein TFAM (
transcription factor A, mitochondrial) stimulated by either
nuclear respiratory factor 1 (NRF1) or NRF2 is a key regulator of mitochondrial biogenesis. Interestingly, the
virus infection at the late stage (at 16 h after
infection) stimulated TFAM expression but decreased the levels of both NRF1 and NRF2, indicating that
virus infection activated TFAM signaling independent of either NRF1 or NRF2. Overall, this study provided evidence that BoHV-1
infection altered the expression of molecules associated with RC complexes,
antioxidant enzymes, and mitochondrial biogenesis-related signaling NRF1/NRF2/TFAM, which correlated with the previous report that
virus infection induces ROS overproduction and
mitochondrial dysfunction.