Mpox virus immunology: exploring links to autoimmune diseases

The reemergence of the mpox virus (MPXV) as a global health threat, with >100 000 cases reported across 115 countries since the WHO's 2022 alert, has intensified research into its pathophysiology. MPXV exists in two main clades with distinct geographic and clinical profiles. Despite progress, the impact of MPXV infection in patients with autoimmune diseases remains underexplored. Emerging data highlight immunomodulatory MPXV proteins that suppress innate immunity and dysregulate adaptive responses, through inhibition of type I interferons, nuclear factor kappa-B, and tumor necrosis factor-α. Intracellular and extracellular virions interfere with antigen presentation, apoptosis, and antigen-presenting cell survival. Certain viral proteins show molecular mimicry with human autoantigens or host regulators, triggering or exacerbating autoinflammatory conditions. Additional mechanisms include epigenetic alterations, immunometabolic reprogramming, and epithelial barrier disruption. This review integrates current evidence on MPXV-autoimmunity interactions, delineates theoretical risks posed by viral immune evasion strategies, and discusses clinical implications for autoimmune patients.