Potential role of EBV reactivation in the development and progression of MS and therapeutic option of fluvoxamine

EBV directly infects resting B cells and epithelial cells, subsequently residing in the infected memory B cells in peripheral blood. These cells express latent membrane protein 2 (LMP-2) and EBV nuclear antigens (EBNAs). Under stress conditions, these B cells can trigger EBV reactivation, leading to severe systemic inflammation, neuronal demyelination, and the potential onset of MS. The interaction of the XBP-1 (X-box binding protein 1) with Sig1R (sigma-1 receptor) on the endoplasmic reticulum (ER) may be implicated in EBV reactivation. Consequently, this hypothesis suggests that sigma-1 receptor agonists like fluvoxamine could help in preventing EBV reactivation, thereby offering therapeutic advantages in the management and progression of MS. This figure incorporates elements from Figure 2 in Hashimoto (2023), with minor modifications, and was designed using resources from Biorender.com.