The cellular localization of avian influenza virus PB1-F2 protein alters the magnitude of IFN2 promoter and NF&#954;B-dependent promoter antagonism in chicken cells.

James, Joe; Smith, Nikki; Ross, Craig; Iqbal, Munir; Goodbourn, Steve; Digard, Paul; Barclay, Wendy S; Shelton, Holly

The cellular localization of avian influenza virus PB1-F2 protein alters the magnitude of IFN2 promoter and NFκB-dependent promoter antagonism in chicken cells.

James, Joe; Smith, Nikki; Ross, Craig; Iqbal, Munir; Goodbourn, Steve; Digard, Paul; Barclay, Wendy S; Shelton, Holly.

Afiliación

James J; 1âThe Pirbright Institute, Pirbright, Woking, UK.
Smith N; 2âImperial College London, London, UK.
Ross C; âPresent address: APHA, Weybridge, UK.
Iqbal M; 3âThe Roslin Institute, Edinburgh, UK.
Goodbourn S; 4âSt George's, University of London, London, UK.
Digard P; 1âThe Pirbright Institute, Pirbright, Woking, UK.
Barclay WS; 4âSt George's, University of London, London, UK.
Shelton H; 3âThe Roslin Institute, Edinburgh, UK.

J Gen Virol ; 100(3): 414-430, 2019 03.

Article en En | MEDLINE | ID: mdl-30672726

RESUMEN

The accessory protein, PB1-F2, of influenza A virus (IAV) functions in a chicken host to prolong infectious virus shedding and thus the transmission window. Here we show that this delay in virus clearance by PB1-F2 in chickens is accompanied by reduced transcript levels of type 1 interferon (IFN)-induced genes and NFκB-activated pro-inflammation cytokines. In vitro, two avian influenza isolate-derived PB1-F2 proteins, H9N2 UDL01 and H5N1 5092, exhibited the same antagonism of the IFN and pro-inflammation induction pathways seen in vivo, but to different extents. The two PB1-F2 proteins had different cellular localization in chicken cells, with H5N1 5092 being predominantly mitochondrial-associated and H9N2 UDL being cytoplasmic but not mitochondrial-localized. We hypothesized that PB1-F2 localization might influence the functionality of the protein during infection and that the protein sequence could alter cellular localization. We demonstrated that the sequence of the C-terminus of PB1-F2 determined cytoplasmic localization in chicken cells and this was linked with protein instability. Mitochondrial localization of PB1-F2 resulted in reduced antagonism of an NFκB-dependent promoter. In parallel, mitochondrial localization of PB1-F2 increased the potency of chicken IFN 2 induction antagonism. We suggest that mitochondrial localization of PB1-F2 restricts interaction with cytoplasmic-located IKKß, reducing NFκB-responsive promoter antagonism, but enhances antagonism of the IFN2 promoter through interaction with the mitochondrial adaptor MAVS. Our study highlights the differential mechanisms by which IAV PB1-F2 protein can dampen the avian host innate signalling response.

Asunto(s)

Subtipo H5N1 del Virus de la Influenza A/metabolismo; Subtipo H9N2 del Virus de la Influenza A/metabolismo; Gripe Aviar/inmunología; Interferón beta/genética; FN-kappa B/genética; Enfermedades de las Aves de Corral/genética; Proteínas Virales/metabolismo; Animales; Pollos; Subtipo H5N1 del Virus de la Influenza A/genética; Subtipo H9N2 del Virus de la Influenza A/genética; Gripe Aviar/genética; Gripe Aviar/virología; Interferón beta/inmunología; FN-kappa B/inmunología; Enfermedades de las Aves de Corral/inmunología; Enfermedades de las Aves de Corral/virología; Regiones Promotoras Genéticas; Proteínas Virales/genética

Palabras clave

IKKß; MAVS; PB1-F2; chicken; influenza virus

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades de las Aves de Corral / Proteínas Virales / FN-kappa B / Interferón beta / Subtipo H5N1 del Virus de la Influenza A / Subtipo H9N2 del Virus de la Influenza A / Gripe Aviar Límite: Animals Idioma: En Revista: J Gen Virol Año: 2019 Tipo del documento: Article Pais de publicación: Reino Unido

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