Epstein-Barr virus hijacks metabolism to transform B-cells

The Epstein-Barr virus (EBV) is a type of herpes virus that causes a very common and highly contagious infection. Some cases lead to mononucleosis (in German: Pfeiffersches Drüsenfieber) and rare cases lead to B-cell lymphoma, a cancer which can affect lymph nodes (Hodgkin lymphoma), blood, and bone marrow, among other tissues. B-cell lymphomas arise from transformed B-cells. Until now, it was unclear how infected B-cells meet the bioenergetic demands to start the multiplication and eventually the transformation of the cells to cancer. 

Bojana Müller-Durovic investigated whether EBV enforces a specific metabolic pathway in freshly infected B-cells that is required for cell-cycle entry and cell division. Her ultimate question: Could these mechanisms be therapeutically blocked? The prize winner and her team used a range of state-of-the-art biotechnological methods, such as metabolic flux analysis, stable-isotope tracing, CRISPR editing, modified viruses, and humanized mouse models. The results of her study showed that EBV induces a specific enzyme (IDO1) which hijacks host tryptophan metabolism. This activates the production of the co-enzyme NAD⁺ that is necessary for mitochondrial energy metabolism and transformation of B-cells. Could this pathway be interrupted by blocking IDO1? In fact, the researcher was able to pharmacologically inhibit IDO1 in mice, which significantly impaired B-cell transformation into cancer cells.

The present investigation showed that EBV reprograms newly infected B-cells by inducing IDO1, which fuels NAD⁺ synthesis and powers the B-cell energy metabolism. This early boost is essential for cell-cycle initiation and B-cell transformation. Pharmacological blockade of IDO1 prevents the growth of lymphoma. The IDO1 inhibition thus proves to be the first virus-specific, metabolism-based strategy for preventing EBV-associated malignancies and offers a new therapeutic approach to fight lymphoma.