Publication: pHERV-W ENV : implicación en la etiopatogenia de la esclerosis múltiple y transactivación por EBV y HHV-6A/B
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2022-06-24
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Universidad Complutense de Madrid
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Abstract
La esclerosis múltiple (EM) es una enfermedad crónica, autoinmune y desmielinizante que afecta al sistema nervioso central. Pese a que se conoce desde hace más de un siglo, existe cierto desconocimiento en torno a su etiopatogenia. Actualmente se considera que determinados factores ambientales desencadenan una respuesta inmunitaria anormal en individuos genéticamente susceptibles de padecer EM. Dentro de estos factores ambientales, los virus han sido uno de los más estudiados; en concreto, el virus de Epstein-Barr (EBV), el herpesvirus humano 6A/B (HHV-6A/B) y el retrovirus asociado a EM (MSRV) – un retrovirus perteneciente a la familia del retrovirus endógeno humano W (HERV-W) – se han propuesto como agentes de riesgo para el desarrollo de EM. A pesar de existir diversas teorías al respecto, no se conoce aún el mecanismo exacto a través del cual estarían actuando. En este contexto, se ha propuesto que estos virus puedan transactivar la expresión de MSRV.Los retrovirus endógenos humanos proceden de retrovirus exógenos que integraron su genoma en las líneas germinales humanas hace millones de años. La familia HERV-W ha sido la más estudiada en relación a la patogenia de la EM. Los dos principales miembros que conforman esta familia son el MSRV y el ERVWE1 (miembro 1 de la familia HERV-W). En concreto, las proteínas de la envuelta de estos retrovirus – pHERV-W ENV y sincitina-1, respectivamente – han centrado muchos de los estudios. Estas proteínas presentan un alto grado de homología, lo que impide su discriminación a nivel proteico. Además, sus propiedades proinflamatorias y neurotóxicas podrían relacionarse con el desarrollo y la progresión de la EM...
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...
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...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, leída el 18-03-2022