A team of Yale School of Medicine infectious diseases researchers recently conducted an in-depth review of the literature on how one genus of viruses, known as flaviviruses, manipulates mitochondria to evade immune responses. Annually, more than 3 billion people are at risk for flavivirus infection, which includes diseases such as yellow fever and dengue fever.

In their review, published in npj Viruses, the authors highlighted key mechanisms used by flaviviruses to evade host immune responses, such as the manipulation of mitochondrial fission and fusion processes to enhance replication, modulation of mitochondrial metabolic pathways, and effects on mitochondrial respiration. The work covered a wide scope of viruses within the genus, detailing the mechanisms used by Zika virus, dengue virus, Japanese encephalitis virus, West Nile virus, tick-borne encephalitis, and yellow fever virus.

Mitochondria, known as the powerhouses of the cell, are key regulators of cellular processes necessary for both cell survival and programmed cell death. They play a critical role in the immune system’s response to viral infections. Accordingly, viral replication and success often depend on a virus’s ability to evade or manipulate these essential regulatory mitochondrial processes.

“From the point of view of the virus, targeting the mitochondria is an efficient way to create a more replication-friendly environment,” said RuthMabel Boytz, a PhD student in the Laurent-Rolle lab and first author. “They are a nexus that flaviviruses can target to simultaneously manipulate multiple cellular processes for their own advantage.”

Maudry Laurent-Rolle, MD, PhD, assistant professor of medicine (infectious diseases) and senior author, said the review is timely given the global threat posed by arboviruses. “It provides a detailed examination of the strategies employed by different flaviviruses to evade the host’s innate immune defenses,” she said. “It also emphasizes the distinct mechanisms utilized by these viruses within the flavivirus genus, shedding light on their unique approaches to immune modulation.”

Laurent-Rolle noted the novel implications of the work. “The review redefines the role of mitochondria, illustrating them as a critical interface between host cells and pathogens,” she said. “By exploring these complex interactions, these studies advance our understanding of mitochondrial involvement in immune responses, offering new perspectives that could inform therapeutic strategies for combating flavivirus infections.”

Yale authors Boytz, Kadiatou Keita, PhD, and Laurent-Rolle are affiliated with the Department of Microbial Pathogenesis.

Yale School of Medicine’s Department of Internal Medicine Section of Infectious Diseases engages in comprehensive and innovative patient care, research, and educational activities for a broad range of infectious diseases. Learn more at Infectious Diseases.