New research from Indiana University microbiologist Cristina Landeta and undergraduate student Rebecca Collins shows that giant viruses carry previously unrecognized tools that may reshape how infected cells regulate redox balance and membrane composition. The study, recently published in Proceedings of the National Academy of Sciences, identifies and functionally characterizes viral homologs of vitamin K epoxide reductase (VKOR), a key enzyme in cellular redox pathways.
Viruses with large DNA genomes are known to encode auxiliary metabolic genes that help reprogram host physiology, but their role in controlling redox homeostasis and membrane biology has remained unclear. Landeta and colleagues addressed this question by combining evolutionary analysis, molecular biology, and functional assays.
The team found that VKOR genes encoded by giant viruses are frequently located alongside genes resembling γ-carboxylase–like epoxidases and fatty acid desaturases, suggesting a coordinated redox pathway for membrane lipid modification. This conserved genomic arrangement points to a modular system that may operate during infection.
The study also examined two giant viruses, Fadolivirus and Yasminevirus, during infection of the amoeba Vermamoeba vermiformis, in collaboration with Bernard La Scola’s group at Aix-Marseille University. The researchers detected expression of VKOR and associated enzymes at both the RNA and protein levels, indicating that these genes are actively deployed during infection. Together, these enzymes may couple vitamin K redox cycling to fatty acid desaturation, potentially altering membrane composition in infected cells.
“This work points to a new way that viruses can influence their hosts,” Landeta said. “Rather than relying solely on host machinery, these viruses appear to encode their own redox modules that may directly shape membrane properties during infection. This is just the beginning of uncovering a new set of tools that viruses use to manipulate their hosts.”
The findings broaden current understanding of how giant viruses interact with their hosts and highlight an additional layer of metabolic complexity in virus–host interactions. By linking vitamin K–dependent redox chemistry to lipid remodeling, the study opens new avenues for exploring how viruses reshape cellular environments to support their replication.
The research underscores the growing recognition that viruses—particularly those with large genomes—can encode sophisticated biochemical pathways, blurring traditional distinctions between viral and cellular metabolism.
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