Viral Triggers of Autoimmune Diseases: Molecular Mechanisms and Sex-Specific Immune Responses - A Comprehensive Review

Autoimmune diseases affect approximately 5–8% of the global population and disproportionately impact females. While genetic susceptibility contributes to disease risk, environmental factors—particularly viral infections—are increasingly recognized as critical triggers of autoimmune pathogenesis. Viruses such as Epstein–Barr virus (EBV), cytomegalovirus (CMV), influenza, and SARS-CoV-2 have been associated with the onset or exacerbation of autoimmune diseases through mechanisms including molecular mimicry, bystander activation, and epitope spreading. Notably, immune responses to viral infections differ significantly between sexes, influenced by sex hormones and X-linked immune gene expression. This review synthesizes current evidence linking viral infections to autoimmune diseases, examines underlying immunological mechanisms, and highlights sex-specific factors that may explain female-biased susceptibility. Emerging multi-omics technologies and clinical implications for prediction and prevention are also discussed.