Figure 7.

Pathogenic potential of HERV-derived Env proteins in autoimmunity. HERV-derived Env proteins have been implicated in the pathological stimulation of the host immunity mainly through two mechanisms: molecular mimicry and superAg activity. In the case of molecular mimicry, Ag-presenting cells (APCs) expose Env epitopes of an exogenous infectious agent by their major histocompatibility complex (MHC), stimulating the specific activation of T CD4+ lymphocytes. In the presence of similarity with HERV-derived proteins, endogenous Env Ags expressed on healthy cells can be cross-recognized by activated T cells, which trigger autoimmunity mechanisms by the release of proinflammatory cytokines and the stimulation of humoral and cellular adaptive responses, leading to tissue injury and destruction. In addition, HERV Env proteins can act as strong activators of the immune system with superAg function, prompting the non-specific stimulation of T lymphocytes. The consequent polyclonal expansion of reactive T cells can led to massive cytokine release, with extensive tissue damage and systemic life-threatening manifestations (shock, multi-organ failure).