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Deciphering the impact of gammaherpesvirus infection on monocyte development and functional reprogramming

par Poncelet, Arthur
Président du jury Le Moine, Alain
Promoteur Goriely, Stanislas ;Machiels, Benedicte
Publication Non publié, 2026-06-04

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Résumé :

The immune system is continuously shaped by microorganisms, with viruses emerging as key drivers of immune variability. Gammaherpesviruses (γ-HVs), including Epstein–Barr virus (EBV), have coevolved with their hosts to establish lifelong infections, and may imprint durable innate immune memory. Using Murid herpesvirus 4 (MuHV-4) in wild-type mice and EBV in humanized models, we show that γ-HVs remodel monocytes and hematopoietic stem cells at phenotypic, transcriptomic, and epigenetic levels, resulting in altered responses to heterologous challenge. Viral persistence is required for immune priming, and IFN-γ signaling directly reprograms myelopoiesis. During latency, virus-specific resident CD8⁺ T cells accumulate in the bone marrow, and remain poised for rapid IFN-γ release. Upon low-dose LPS stimulation, monocyte-derived IL-27, IL-18, and IL-12 promote bystander IFN-γ secretion from these CD8+ T cells, amplifying myelopoietic rewiring. Thus, γ-HV latency establishes a cytokine circuit that shapes innate immune training and defines a new equilibrium between host and persistent viruses.