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Affinity Purification of Influenza Virus Ribonucleoprotein Complexes from the Chromatin of Infected Cells

Affinity Purification of Influenza Virus Ribonucleoprotein Complexes from the Chromatin of Infected Cells

Published on: June 3, 2012

Una región de codificación de proteínas superpuestas en el segmento 3 del virus de la influenza A modula la respuesta

B W Jagger¹, H M Wise, J C Kash

¹Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.

Science (New York, N.Y.)

|June 30, 2012

Resumen

Los científicos descubrieron una nueva proteína, PA-X, en el virus de la influenza A (IAV) que reduce su patogenicidad. Este hallazgo arroja luz sobre cómo el virus afecta la respuesta del huésped durante la infección.

Área de la Ciencia:

Virología Virología.
Biología Molecular Biología Molecular
Inmunología Inmunología.

Sus antecedentes:

La patogenicidad del virus de la influenza A (VIA) es variable y no se comprende completamente.
IAV confía en sus segmentos genéticos para la replicación y la virulencia.
La respuesta del huésped a la infección por VAI implica vías celulares complejas.

Objetivo del estudio:

Identificar nuevas proteínas virales que contribuyen a la patogenicidad del VAI.
Para investigar la función de una proteína recién identificada derivada del segmento 3 de IAV.
Para entender el papel de esta proteína en la modulación de la expresión génica del huésped y la virulencia de IAV.

Principales métodos:

Análisis del segmento 3 de IAV para identificar marcos de lectura abiertos (ORF).
Detección de cambio de marco ribosómico para acceder a un segundo ORF (X-ORF).
Caracterización del producto de cambio de marco, denominado PA-X, y su función.
Evaluación del impacto de PA-X en la expresión génica del huésped.
Evaluación del papel de PA-X en la virulencia de IAV utilizando un modelo de infección de ratón.

Principales resultados:

Se identificó un segundo marco de lectura abierto (X-ORF) en el segmento 3 del IAV, al que se accedió a través del cambio de marco ribosómico.
El producto del cambio de marco, PA-X, combina el dominio de la endonucleasa de la proteína PA con una nueva región C-terminal.
PA-X funciona para reprimir la expresión génica celular del huésped.
Se descubrió que PA-X disminuye la patogenicidad de IAV en un modelo de ratón.
La pérdida de la expresión de PA-X alteró la cinética de la respuesta del huésped, aumentando las vías inflamatorias, apoptóticas y de señalización de los linfocitos T.

Conclusiones:

Se ha identificado una proteína IAV previamente desconocida, PA-X.
PA-X modula la patogénesis de IAV mediante la represión de la expresión génica del huésped y la disminución de la virulencia.
El descubrimiento de PA-X proporciona nuevos conocimientos sobre las interacciones del IAV con el huésped y la patogénesis.
Comprender el papel de PA-X tiene implicaciones significativas para el desarrollo de estrategias contra la infección por VAI.

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