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La supresión de la respuesta antiviral por una histona de imitación de la gripe
Ivan Marazzi1, Jessica S Y Ho, Jaehoon Kim
1Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA. imarazzi@rockefeller.edu
Nature
|March 16, 2012
Resumen
La proteína NS1 del virus de la gripe imita a las histonas para unirse al complejo hPAF1C, suprimiendo la expresión génica antiviral. Esta interacción debilita al huésped.
Área de la Ciencia:
- Virología Virología.
- Biología Molecular Biología Molecular
- La epigenética es la epigenética.
Sus antecedentes:
- Las infecciones virales secuestran las proteínas del huésped para manipular los procesos celulares.
- Se sabe que la proteína no estructural 1 (NS1) del virus de la gripe interfiere con las defensas del huésped.
Objetivo del estudio:
- Para dilucidar un nuevo mecanismo de patogénesis del virus de la gripe que involucra la epigenética del huésped.
- Investigar la interacción entre la influenza NS1 y el complejo de alargamiento de transcripción PAF1 humano (hPAF1C).
Principales métodos:
- Análisis de la secuencia de proteínas de la influenza A H3N2 NS1 para los motivos similares a las histonas.
- Pruebas bioquímicas para demostrar la unión de NS1 a hPAF1C.
- Evaluación del papel de hPAF1C en la respuesta antiviral y la gravedad de la infección por influenza.
Principales resultados:
- La proteína influenza NS1 contiene una secuencia que imita la histona.
- NS1 se une a hPAF1C a través de su imitación de histona, inhibiendo el alargamiento transcripcional.
- hPAF1C es esencial para la expresión génica antiviral; su deficiencia aumenta la susceptibilidad viral.
Conclusiones:
- El virus de la gripe utiliza una imitación de histona en NS1 para atacar a hPAF1C, suprimiendo las respuestas antivirales del huésped.
- Dirigirse a hPAF1C le permite al virus modular selectivamente la expresión génica y evadir la inmunidad.
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