A metabolic dependency of EBV can be targeted to hinder B cell transformation, 2024, BOJANA MÜLLER-DUROVIC et al

Abstract
Following infection of B cells, Epstein Barr virus (EBV) engages host pathways that mediate cell proliferation and transformation, contributing to the propensity of the virus to drive immune dysregulation and lymphomagenesis.

We found that the EBV protein EBNA2 initiates NAD de novo biosynthesis by driving expression of the metabolic enzyme IDO1 in infected B cells. Virus-enforced NAD production sustained mitochondrial complex I activity, to match ATP-production with bioenergetic requirements of proliferation and transformation. In transplant patients, IDO1 expression in EBV-infected B cells, and a serum signature of increased IDO1 activity, preceded development of lymphoma. In humanized mice infected with EBV, IDO1 inhibition reduced both viremia and lymphomagenesis.

Virus-orchestrated NAD biosynthesis is, thus, a druggable metabolic vulnerability of EBV-driven B cell transformation—opening therapeutic possibilities for EBV-related diseases.

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https://scitechdaily.com/turning-the-tide-against-epstein-barr-virus-with-repurposed-drugs/

Researchers led by Professor Christoph Hess have deciphered how the immune cells infected with EBV —the so-called B cells — are reprogrammed. Known as “transformation,” this process is necessary for the infection to become chronic and cause subsequent diseases such as cancer. Specifically, the team discovered that the virus triggers the infected cell to ramp up the production of an enzyme known as IDO1. This ultimately leads to greater energy production by the power plants of infected cells: the mitochondria. In turn, this additional energy is needed for the increased metabolism and the rapid proliferation of B cells reprogrammed by EBV in this way.
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“Previously, IDO1 inhibitors have been developed in the hope that they could help to treat established cancer — which has unfortunately turned out not to be the case. In other words, there are already clinically tested inhibitors against this enzyme,”