*5.5. Measles*

Measles virus consists of a negative-sense RNA genome that causes highly contagious respiratory sickness including pneumonia, seizures, brain damage, and even death. The attenuated measles virus of the Edmonston strain (MV-Edm) activates p62-mediated mitophagy in non-small-cell lung cancer (NSCLC) cells by disrupting MAVS and resulting in the significant inhibition of type I IFN responses [134]. It utilizes apoptosis to sustain viral propagation and replication [135]. Defects in autophagy resulted in decreased viral titers and MV-Edm induced cell death in NSCLC cells. When p62 expression was silenced, it led to the restoration of mitochondrial mass in MV-Edm-infected cells and inhibition of mitophagy. Therefore, it appears that MV usurps mitophagy to mitigate the RIG-I/MAVSmediated innate immune signaling pathways [134].

#### **6. Concluding Remarks**

Despite the exhilarating scientific advances in recent times that have identified many important metabolic pathways that might be targets in order to enhance immune responses, there continue to be new and exciting questions. Various aspects of mitochondrial dynamics, including mitophagy, have been of great interest, with recent studies showing that viruses circumvent host innate immune responses through altering mitochondrial functions. Viral infections induce metabolic re-programming, resulting in discrete bioenergetic phenotypes, strategically utilizing them for viral propagation and replication. Viruses exploit RIG-I-MDA5-MAVS antiviral signaling pathways and aim at disrupting mitochondrial membrane potential, mitochondrial-associated proteins and mitochondrial dynamics that essentially impede virus-induced type I IFN responses. Undeniably, there exists an intimate association between mitochondrial dynamics and viral infections. However, more compre-

hensive mechanistic studies and their significance to chronic pathology are necessary in understanding complex viral life cycle processes. A deeper understanding of tightly regulated mitochondrial functions such as bioenergetics, innate antiviral immunity, apoptosis, and inter-organelle cross-talk needs to be extensively investigated to analyze their effect on viral infections. The ultimate goal of identifying mechanisms, which may differ with individual viruses, may provide important information for targeted therapeutic interventions to redirect the immune response toward a less pathogenic response.

**Author Contributions:** S.E. and N.W.L. have conceptualized and written the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** Authors acknowledge the support from NIH/NIAID grant funding (RO1HL144858 and RO1AI036302) and the Mary H. Weiser Food Allergy Center at the University of Michigan.

**Conflicts of Interest:** The authors declare no conflict of interest.
