Reactive oxygen species activate NFκB (p65) and p53 and induce apoptosis in RVFV infected liver cells

- MP12 strain of Rift Valley fever virus induces oxidative stress in liver cells at early time points following infection.
- The viral protein NSs appears to localize in mitochondria of infected cells.
- Oxidative stress results in activation of p65 and p53.
- Inflammatory gene expression precedes the onset of apoptosis in MP12 infected cells.
- Use of antioxidants at early stages of infection ameliorates oxidative stress related deleterious effects in infected liver cells.

Rift Valley fever virus (RVFV) infection is often associated with pronounced liver damage. Previously, our studies revealed altered host phospho-signaling responses (NFκB, MAPK and DNA damage responses) in RVFV infected epithelial cells that correlated with a cellular stress response. Here, we report that RVFV infection of liver cells leads to an increase in reactive oxygen species (ROS). Our data suggests the presence of the viral protein NSs in the mitochondria of infected cells, hence contributing to early increase in ROS. Increased ROS levels correlated with activation of NFκB (p65) and p53 responses, which in conjunction with infection, was also reflected as macromolecular rearrangements observed using size fractionation of protein lysates. Additionally, we documented an increase in cytokine expression and pro-apoptotic gene expression with infection, which was reversed with antioxidant treatment. Collectively, we identified ROS and oxidative stress as critical contributors to apoptosis of liver cells during RVFV infection.