Retroviral envelope proteins: Involvement in neuropathogenesis

The primary disease caused by infection with the exogenous human retroviruses, human immunodeficiency virus 1 (HIV-1) or human T-cell lymphotropic virus 1 (HTLV-1), may overlay manifestations of additional autoimmune pathogenesis. Currently, a role for human endogenous retroviruses (HERVs) is also emerging in some autoimmune/immune-mediated diseases, particularly in multiple sclerosis (MS). Both exogenous and endogenous retroviruses have the potential to elicit the processes leading to autoimmune disease. The pathogenicity of the retroviral envelope protein (Env) is a key player with notable importance in neuroimmune diseases. An essential prerequisite of retroviral infection is the interactions between Env (the retroviral adhesion) proteins on the virion and specific surface receptors on the host cell. These interactions facilitate fusion of the viral envelope and cellular membranes. Additional fusiogenic activities mediated by Env may be beneficial (establishment of the syncytiotrophoblast induced by a HERV-encoded Env) or detrimental to the host (syncytia formation, induction of apoptosis), and Envs are further implied in the direct induction of proinflammatory cytokines, the regulation of autophagy, and pathways of cell death. The pathogenic potential of retroviral Env is therefore not limited to the pathogenetics of infection but also comprise the pathogenic/toxic capacity of the Env protein itself.