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CRG (Centro de Regulación Genómica)

CRG (Centro de Regulación Genómica)

The Centre for Genomic Regulation (CRG) is an innovative centre for basic research created in December 2000 by initiative of the former Department of Universities, Research and Information Society (DURSI) of the Catalan Government. The CRG is legally constituted as a non-profit foundation and has the participation from the Catalan Government through the Economy and Knowledge Department (DECO) and the Health Department (DS), as well as from the Pompeu Fabra University (UPF), and the Spanish Ministry of Economy & Competitiveness (MINECO). It is an international biomedical research institute of excellence whose mission is to discover and advance knowledge for the benefit of society, public health and economic prosperity. The CRG believes that the medicine of the future depends on the groundbreaking science of today. This requires an interdisciplinary scientific team focused on understanding the complexity of life from the genome to the cell to a whole organism and its interaction with the environment, offering an integrated view of genetic diseases. The Centre for Genomic Regulation (CRG) is located at numer 88 of Dr. Aiguader St., in the 4th, 5th and 6th floor (7,500 m2) of the Parc de Recerca Biomedica de Barcelona, PRBB (Barcelona Biomedical Research Park) building. http://www.crg.eu

Una nueva herramienta para encontrar el VIH latente mejorará las estrategias actuales de tratamiento contra el sida

Fuente: CRG-UPF | Publicado: 23-11-2016
Un grupo de investigadores del Centro de Regulación Genómica (CRG) y de la Universidad Pompeu Fabra (UPF) en Barcelona ha desarrollado una nueva tecnología que arroja luz sobre la infección por el VIH e impulsará la investigación para el desarrollo de fármacos.
La investigación, publicada en la revista Nature Structural and Molecular Biology, muestra que la respuesta del VIH latente a las terapias de reactivación depende en parte del sitio del genoma humano en el que se integra el ADN vírico.
Derechos: B-­HIVE Draw: Representación artística del proyecto B-­HIVE de identificación de los virus VIH latentes en el genoma humano y caracterización de su expresión génica. Autor: Heng-­Chang Chen.
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Un grupo de investigadores del Centro de Regulación Genómica (CRG) y de la Universidad Pompeu Fabra (UPF) en Barcelona ha desarrollado una nueva tecnología que arroja luz sobre la infección por VIH y ofrece el primer retrato de la expresión del VIH en el genoma humano.



Cuando el virus del VIH entra en el genoma, una parte de los virus se inactiva, quedando latentes, y evitan que el sistema inmune los detecte. Así escapan a las terapias y siguen siendo una amenaza para el paciente, porque en cualquier momento pueden despertar y reiniciar el ciclo de infección espontáneamente.


Muchas de las terapias y fármacos disponibles actualmente intentan reactivar el VIH latente con la esperanza de eliminar toda la población de virus latentes. Desafortunadamente, ninguna de las terapias propuestas ha resultado eficaz en la cura de pacientes infectados.



El ADN externo se encuentra silenciado en el genoma humano por la cromatina huésped, que está compuesta por ADN y proteínas que lo envuelven y condensan para formar los cromosomas. El silenciamiento de la cromatina está mediado por varios mecanismos y, ahora, un equipo de investigadores liderado por Guillaume Filion, líder del grupo del laboratorio de Arquitectura Genómica del CRG, ha desarrollado una tecnología para descubrir el papel que juega el silenciamiento de la cromatina en la respuesta del VIH latente frente a los fármacos disponibles en la actualidad.



Tal y como aparece en Nature Structural and Molecular Biology, el equipo científico ha desarrollado una tecnología llamada B-HIVE, que les ha permitido cartografiar los fragmentos de VIH insertados en el genoma humano, así como medir sus niveles de expresión. “Hemos identificado mediante un ‘código de barras’ una población de virus gracias a un identificador genético. Con estos ‘códigos de barras’ pudimos vincular cada virus con su localización cromosómica”, explica Filion, autor principal del estudio.


Los ‘códigos de barras’ genéticos funcionan como los códigos de barras de los productos alimenticios en los supermercados: cuando todos los artículos están etiquetados, cada artículo individual puede ser identificado por su código específico. “Además, hemos sido capaces de medir sus niveles de expresión y demostrar que la respuesta del VIH a las terapias de reactivación depende en parte del sitio de integración en el genoma humano. Demostramos por primera vez la importancia real de la importancia del contexto de la cromatina en la lucha contra el sida”, afirma el investigador.


Gracias a esta nueva tecnología, los investigadores han podido demostrar que los medicamentos que funcionan reactivando el VIH lo hacen desde diferentes sitios dentro del cromosoma. En otras palabras, estos fármacos son más selectivos de lo que se pensaba anteriormente. “Con esta técnica a nuestro alcance, ahora podemos buscar la mejor combinación de fármacos que puedan reactivar todos los virus latentes que hasta ahora escapaban a los medicamentos antirretrovirales en uso hoy en día y hacerlos susceptibles de ser destruidos. Nuestro estudio sugiere que es necesario orientar las futuras investigaciones hacia el desarrollo de fármacos que incluyan dianas complementarias”, dice Heng-Chang Chen, investigador del CRG y primer autor del estudio. “Éste es un gran paso adelante y sin duda impulsará la investigación hacia la cura del VIH, así como nuestra comprensión del estado inactivo del VIH latente”, añade con entusiasmo Andreas Meyerhans, coautor del artículo e investigador ICREA en la UPF.



Los nuevos mapas de la expresión del VIH en todo el genoma que resultan de este estudio abordan una cuestión fundamental que hasta ahora no había sido resuelta y permiten visualizar un principio básico de la regulación genética.


Será un recurso muy útil para los analistas de datos interesados en aplicaciones clínicas. Aunque parece que comienza una época emocionante para los investigadores, aún queda esperar para ver cómo estos esperanzadores resultados se traducen en beneficios  para el colectivo de personas afectadas por el VIH.


Trabajo de referencia: Chen HC et al. “Position effects influence HIV latency reversal”, Nature Structural and Molecular Biology, November 21 2016. DOI: nsmb.3328
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