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El origen recombinante del retrovirus XMRVV
Tobias Paprotka1, Krista A Delviks-Frankenberry, Oya Cingöz
1Viral Mutation Section, HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Science (New York, N.Y.)
|June 2, 2011
Resumen
El virus relacionado con el virus de la leucemia murina xenotrópica (XMRV) probablemente surgió de la recombinación de dos provirus en ratones durante el paso del tumor. Esto sugiere XMRVV.
Área de la Ciencia:
- Virología Virología.
- Oncología Oncología.
- Genética La genética.
Sus antecedentes:
- La detección del virus relacionado con el virus de la leucemia murina xenotrópica (XMRV) en muestras humanas ha sido controvertida debido a la falta de replicación.
- Estudios previos informaron sobre el XMRV en pacientes con cáncer de próstata y síndrome de fatiga crónica.
- El origen y el mecanismo de generación del XMRV siguen sin estar claros.
Objetivo del estudio:
- Para investigar el origen y la generación de XMRV.
- Para entender cómo surgió el XMRV en líneas celulares de cáncer de próstata humano y en xenografts.
- Para explicar los hallazgos discrepantes con respecto a la presencia de XMRV en muestras humanas.
Principales métodos:
- Se estudiaron las líneas celulares de cáncer de próstata humano (CWR22Rv1, CWR-R1) y su xenograft progenitor (CWR22) pasado en ratones.
- Analizó la presencia viral en pasajes tempranos y tardíos de xenografts y líneas celulares.
- Secuenciaron los provirus del ratón huésped (PreXMRV-1, PreXMRV-2) y los compararon con el XMRV.
Principales resultados:
- El XMRV se detectó en las líneas celulares CWR22Rv1, CWR-R1 y en los xenografts de paso posterior, pero no en los primeros pasos.
- Se identificaron dos provirus de ratón, PreXMRV-1 y PreXMRV-2, que comparten una identidad del 99,92% con el XMRV.
- El XMRV no estaba presente en el tumor CWR22 original, lo que indica que se generó durante el paso.
Conclusiones:
- El XMRV se originó a partir de un evento de recombinación entre dos provirus de ratón durante el paso del tumor.
- La generación independiente de un recombinante idéntico es muy improbable.
- La contaminación de muestras humanas con este XMRV generado por ratones probablemente explica su asociación con enfermedades humanas.
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