The Role of Mitochondrial Antiviral Signaling Protein (MAVS) in Mitochondrial Funtions

Abstract

Infectious diseases account for more than 13 million deaths every year, which makes it apparent that infectious diseases are a tremendous burden for the society. Much research has therefore been aimed to elucidate the immune responses against pathogens. The mitochondrial antiviral signaling protein (MAVS) has been found to be essential for the antiviral innate immunity. Hou et al. recently described that activation of the antiviral innate immunity pathways activates MAVS by causing them to form aggregates capable of activating downstream signaling resulting in production of interferons that mediate the antiviral response. The aim of this study was to assess how MAVS and innate immune signaling intersect with mitochondrial functions in Huh7 and HEK293 cells. We wanted to isolate SeV-induced MAVS aggregation in these cells. We further wanted to elucidate a possible association between MAVS aggregates and autophagy, which would indicate that MAVS aggregates are targeted for autophagic degradation upon SeV infection. We found that SeV infection and MAVS overexpression are involved in regulation of Nrf2-mediated stress responses. However, we did not detect any change in ROS production upon SeV infection or MAVS overexpression. We were able to detect SeV-induced MAVS aggregation in both Huh7 and HEK293 cells, which confirms that MAVS forms aggregates upon infection. In addition we achieved results indicating that MAVS and p62 are associated upon SeV infection, suggesting that p62 may target MAVS for autophagic degradation after a viral infection has been encountered. These results may contribute to a better understanding of the molecular mechanisms of MAVS.