Flaviviridae and mitochondria: Everything you always wanted to know about their relationship but were afraid to ask.

Infections with Flaviviridae constitute a major public health concern, especially considering the limited availability of prophylactic and therapeutic treatments. Most notably, the recent emergence of Zika virus in the Americas was associated with the dramatic increase of severe symptoms such as congenital microcephaly, while hepatitis C virus causes the death of approximately 300,000 individuals annually. Flaviviridae have evolved to hijack cellular organelles and to favor their replication, often via divergent molecular mechanisms. In addition to the remodeling of the endoplasmic reticulum, which is required for the replication of the viral genome and the assembly of the neosynthesized virions, Flaviviridae induce drastic morphological alterations of the mitochondria. This is associated with the viral co-opting of several key mitochondrial functions in apoptosis, innate immunity and metabolism. This review recapitulates the current knowledge about the morphological and functional relationship between Flaviviridae and mitochondria and explains how this contributes to the establishment of a cytoplasmic environment which is favorable to viral replication.