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El poliomavirus humano, JCV, utiliza los receptores de serotonina para infectar las células
Gwendolyn F Elphick1, William Querbes, Joslynn A Jordan
1Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.
Science (New York, N.Y.)
|November 20, 2004
Resumen
El receptor de serotonina 5HT2A es el punto de entrada celular para el virus John Cunningham (JCV), que causa leucoencefalopatía multifocal progresiva. El bloqueo de este receptor puede tratar esta enfermedad cerebral fatal.
Área de la Ciencia:
- Neurovirología La neurovirología.
- Biología molecular y celular Biología molecular y celular.
- Inmunología Inmunología.
Sus antecedentes:
- La leucoencefalopatía multifocal progresiva (LMP) es una enfermedad desmielinizante fatal causada por el virus John Cunningham (JCV) en individuos inmunocomprometidos.
- La identificación del receptor celular para el JCV es crucial para comprender la entrada viral y desarrollar estrategias terapéuticas.
Objetivo del estudio:
- Para identificar el receptor celular utilizado por el JCV para entrar en las células gliales humanas.
- Investigar el potencial de dirigirse a este receptor para la intervención terapéutica contra la LMP.
Principales métodos:
- Utilizó antagonistas del receptor 5HT2A y anticuerpos monoclonales para bloquear la infección por JCV.
- Realizó experimentos de transfección con células negativas para el receptor 5HT2A.
- Los empleados etiquetaron los receptores 5HT2A y etiquetaron JCV para rastrear la internalización y localización viral.
Principales resultados:
- El receptor de serotonina 5HT2A (5HT2AR) fue identificado como el receptor celular para el JCV en las células gliales humanas.
- Los antagonistas y anticuerpos del receptor 5HT2A inhibieron significativamente la infección por el VHC.
- La transfección de células negativas para el receptor 5HT2A con 5HT2AR restauró la infectividad del VHC, que luego fue bloqueada por los anticuerpos.
- El JCV internalizado colocalizado con los receptores 5HT2A en los compartimentos endosómicos.
Conclusiones:
- El receptor 5HT2A es esencial para la entrada del JCV en las células gliales humanas.
- La orientación del receptor 5HT2A con antagonistas o anticuerpos es prometedora para el tratamiento de la leucoencefalopatía multifocal progresiva.
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