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Apobec3 codifica Rfv3, un gen que influye en el control de anticuerpos neutralizantes de la infección por retrovirus
Mario L Santiago1, Mauricio Montano, Robert Benitez
1Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA.
Science (New York, N.Y.)
|September 6, 2008
Resumen
El gen para la resistencia al virus Friend (Rfv3) es Apobec3, crucial para neutralizar las infecciones retrovirales. Su inactivación causa susceptibilidad, mientras que su función adecuada proporciona protección al huésped contra retrovirus como el VIH.
Área de la Ciencia:
- Inmunología Inmunología.
- Virología Virología.
- Genética La genética.
Sus antecedentes:
- La base genética de la resistencia al Friend virus 3 (Rfv3) se ha buscado durante 30 años.
- Rfv3 influye en las respuestas de anticuerpos y la viremia contra los retrovirus.
Objetivo del estudio:
- Para identificar la identidad molecular del gen Rfv3.
- Para aclarar el mecanismo de la resistencia retroviral conferida por Rfv3.3.
Principales métodos:
- La clonación posicional y el mapeo genético para identificar el locus Rfv3.
- Inactivación genética de genes candidatos en ratones.
- Análisis de la expresión del gen Apobec3 y el empalme en cepas resistentes y susceptibles.
- Evaluación de las respuestas de anticuerpos neutralizantes retrovirales y la viremia.
Principales resultados:
- Rfv3 fue identificado como el gen Apobec3, localizado en la misma región cromosómica.
- La inactivación genética de Apobec3 hizo que los ratones resistentes a Rfv3 fueran susceptibles al virus Friend.
- Se observó un empalme aberrante del ARNm de Apobec3 en cepas de ratón sensibles al Rfv3.
- Apobec3 demostró una amplia actividad inhibidora contra los retrovirus, incluido el VIH.
Conclusiones:
- Apobec3 es el determinante molecular del rasgo de resistencia Rfv3.
- Los mecanismos dependientes de Apobec3 contribuyen a la protección del huésped contra las infecciones retrovirales.
- Los hallazgos sugieren un papel potencial para Apobec3 en las infecciones retrovirales humanas como el VIH.
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