The AI & Systems Bioinformatics Unit of the Translational Neuropharmacology Lab has released a new preprint introducing VirTarget, the first virus-informed pharmacogenomics framework designed to systematically evaluate how multiple sclerosis (MS) immunotherapies interact with Epstein-Barr virus (EBV)-driven pathogenesis.
While EBV is increasingly recognized as a central driver of MS, current immunotherapies are prescribed without considering their effects on viral-host interactions or how they modulate EBV-related genetic risk factors. To address this critical gap, VirTarget integrates three complementary analytical layers: EBV-host interactomics mapping viral-host protein interactions within MS-relevant pathways, host genetic susceptibility linking MS risk variants to EBV-targeted therapy-modulated networks, and transcriptomic directionality analysis that classifies therapies as reinforcers or reversers of the MS-EBV signature.
Our systematic evaluation of approved MS immunotherapies revealed substantial heterogeneity in their engagement with the MS-EBV network. Dimethyl fumarate showed the strongest and broadest network engagement, followed by natalizumab and interferons, while anti-CD20 antibodies and S1P modulators exhibited weaker effects on EBV-related pathways. Notably, therapies converged on critical MS risk genes including HLA-DRB1, IL7R, IL2RA, CD40, and TYK2, which are directly targeted by EBV proteins within therapy-modulated pathways. Multiple therapies reversed EBV-driven dysregulation of cytokine and innate immune pathways, suggesting their benefits extend to counteracting viral-mediated immune modulation.
VirTarget establishes a foundation for precision treatment strategies in MS, where therapeutic selection can be informed by patient viral serostatus, individual genetic susceptibility profiles, and system-level transcriptomic responses. This systems-level approach represents a paradigm shift toward virus-informed precision medicine in MS and other EBV-associated autoimmune diseases.
Read the full pre-print: Altas B, Georgiou P, Onisiforou M, Zanos P, Onisiforou A. VirTarget: Virus-Informed Pharmacogenomics Framework Identifies Immunotherapies That Mitigate Epstein-Barr Virus-Driven Dysregulation in Multiple Sclerosis. bioRxiv (2025). doi: 10.1101/2025.11.03.686445
This work was led by Dr. Anna Onisiforou, head of the AI & Systems Bioinformatics Unit.