Artículo
Influenza NS1 directly modulates Hedgehog signaling during infection
Smelkinson, Margery G.; Guichard, Annabel; Teijaro, John R.; Malur, Meghana; Loureiro, Maria Eugenia
; Jain, Prashant; Ganesan, Sundar; Zuniga, Elina Isabel
; Krug, Robert M.; Oldstone, Michael B.; Bier, Ethan
Fecha de publicación:
08/2017
Editorial:
Public Library of Science
Revista:
Plos Pathogens
ISSN:
1553-7366
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The multifunctional NS1 protein of influenza A viruses suppresses host cellular defense mechanisms and subverts other cellular functions. We report here on a new role for NS1 in modifying cell-cell signaling via the Hedgehog (Hh) pathway. Genetic epistasis experiments and FRET-FLIM assays in Drosophila suggest that NS1 interacts directly with the transcriptional mediator, Ci/Gli1. We further confirmed that Hh target genes are activated cell-autonomously in transfected human lung epithelial cells expressing NS1, and in infected mouse lungs. We identified a point mutation in NS1, A122V, that modulates this activity in a context-dependent fashion. When the A122V mutation was incorporated into a mouse-adapted influenza A virus, it cell-autonomously enhanced expression of some Hh targets in the mouse lung, including IL6, and hastened lethality. These results indicate that, in addition to its multiple intracellular functions, NS1 also modifies a highly conserved signaling pathway, at least in part via cell autonomous activities. We discuss how this new Hh modulating function of NS1 may influence host lethality, possibly through controlling cytokine production, and how these new insights provide potential strategies for combating infection.
Palabras clave:
Influenza
,
Ns1
,
Hedgehog
,
Development
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Identificadores
Colecciones
Articulos(ICT - MILSTEIN)
Articulos de INST.DE CS. Y TECNOLOGIA "DR. CESAR MILSTEIN"
Articulos de INST.DE CS. Y TECNOLOGIA "DR. CESAR MILSTEIN"
Citación
Smelkinson, Margery G.; Guichard, Annabel; Teijaro, John R.; Malur, Meghana; Loureiro, Maria Eugenia; et al.; Influenza NS1 directly modulates Hedgehog signaling during infection; Public Library of Science; Plos Pathogens; 13; 8; 8-2017; 1-24; e1006588
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