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Análisis genómico del aumento de las respuestas inmunes del huésped y la muerte celular inducida por el virus de la

John C Kash¹, Terrence M Tumpey, Sean C Proll

¹Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195, USA. jkash@u.washington.edu

|September 29, 2006

Resumen

La pandemia de gripe de 1918 fue la pandemia de gripe de 1918.

Área de la Ciencia:

Virología Virología.
Inmunología Inmunología.
Patología Patología Patología.

Sus antecedentes:

La pandemia de influenza de 1918 causó aproximadamente 50 millones de muertes en todo el mundo.
El daño pulmonar severo, incluida la bronquitis aguda, la alveolitis, el edema pulmonar y la hemorragia, caracterizaron la patología.
El papel de la respuesta inmune del huésped en esta patología grave no se entiende bien.

Objetivo del estudio:

Para analizar exhaustivamente la respuesta global del huésped al virus de la gripe de 1918.
Para investigar la contribución de las respuestas inmunes del huésped a la virulencia del virus de la influenza de 1918.
Comprender los mecanismos subyacentes a la patología severa de la gripe para posibles objetivos terapéuticos.

Principales métodos:

Reconstrucción del virus de la gripe de 1918.
Infección de ratones con el virus de 1918 completamente reconstruido y virus con subconjuntos de genes.
Análisis exhaustivo de la respuesta global del huésped a nivel genómico.
Análisis histopatológico de tejidos pulmonares de ratones infectados.

Principales resultados:

Los ratones infectados con el virus de 1918 completamente reconstruido mostraron una activación acelerada y aumentada de los genes de respuesta inmune.
Las vías proinflamatorias y de muerte celular se activaron significativamente en 24 horas, persistiendo hasta la muerte.
La infección con subconjuntos de genes de 1918 resultó en una patología más leve y una mortalidad retardada.
Se observó evidencia de interacción cooperativa entre los genes de la influenza de 1918.

Conclusiones:

El estudio de la virulencia del virus de la influenza de 1918 requiere el uso del virus completamente reconstruido.
Las respuestas inmunes del huésped juegan un papel crítico en la patología severa de la pandemia de 1918.
Comprender estas respuestas es vital para identificar indicadores de pronóstico y desarrollar terapias antivirales contra futuras pandemias.

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