PHERV-W ENV :Implicación en la etiopatogenia de la esclerosis múltiple y transactivación por EBV y HHV-6A/B

Résumé

Multiple sclerosis (MS) is a chronic, autoimmune and demyelinating disease that affects the central nervous system. Despite being known for more than a century, its etiopathogenesis is still partially unknown. Nowadays, certain environmental factors are thought to trigger an abnormal autoimmune response in genetically susceptible individuals to MS. Viruses have been one of the most studied environmental factors; specifically, Epstein-Barr virus (EBV), human herpesvirus 6A/B (HHV-6A/B) and MS-associated retrovirus (MSRV) – a retrovirus belonging to the human endogenous retrovirus W (HERV-W) family – have been proposed as risk agents for MS development. While there are several theories, the actual mechanism by which they would be acting is still unknown. In this context, it has been proposed that those viruses could transactivate MSRV expression.Human endogenous retroviruses come from exogenous retroviruses that integrated their genome into human germ lines millions of years ago. The HERV-W family has been the most studied one in relation to the pathology of MS. The two main members that make up this family are MSRV and ERVWE1 (HERV-W family member 1). In particular, the envelope proteins of these retroviruses – pHERV-W ENV and syncytin-1, respectively – have focused many of those studies. These proteins show a high degree of homology, which hinders their discrimination at the protein level. Moreover, their proinflammatory and neurotoxic properties could lead to the development and progression of MS...