Shortening the unstructured, interdomain region of the non-structural protein NS1 of an avian H1N1 influenza virus increases its replication and pathogenicity in chickens.

Trapp, Sascha; Soubieux, Denis; Marty, Hélène; Esnault, Evelyne; Hoffmann, Thomas W; Chandenier, Margaux; Lion, Adrien; Kut, Emmanuel; Quéré, Pascale; Larcher, Thibaut; Ledevin, Mireille; Munier, Sandie; Naffakh, Nadia; Marc, Daniel

Trapp, Sascha; Soubieux, Denis; Marty, Hélène; Esnault, Evelyne; Hoffmann, Thomas W; Chandenier, Margaux; Lion, Adrien; Kut, Emmanuel; Quéré, Pascale; Larcher, Thibaut; Ledevin, Mireille; Munier, Sandie; Naffakh, Nadia; Marc, Daniel.

Afiliación

Trapp S; UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.
Soubieux D; Equipe PIA, UMR1282 Infectiologie et Santé Publique, INRA, 37380 Nouzilly, France.
Marty H; Equipe BioVA, UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, 37380 Nouzilly, France.
Esnault E; UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.
Hoffmann TW; Equipe PIA, UMR1282 Infectiologie et Santé Publique, INRA, 37380 Nouzilly, France.
Chandenier M; UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.
Lion A; Equipe PIA, UMR1282 Infectiologie et Santé Publique, INRA, 37380 Nouzilly, France.
Kut E; UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.
Quéré P; Equipe PIA, UMR1282 Infectiologie et Santé Publique, INRA, 37380 Nouzilly, France.
Larcher T; Equipe BioVA, UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, 37380 Nouzilly, France.
Ledevin M; UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.
Munier S; Equipe BioVA, UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, 37380 Nouzilly, France.
Naffakh N; UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.
Marc D; UMR1282 Infectiologie et Santé Publique, Université François Rabelais de Tours, 37000 Tours, France.

J Gen Virol ; 95(Pt 6): 1233-1243, 2014 Jun.

Article en En | MEDLINE | ID: mdl-24694396

RESUMEN

Currently circulating H5N1 influenza viruses have undergone a complex evolution since the appearance of their progenitor A/Goose/Guangdong/1/96 in 1996. After the eradication of the H5N1 viruses that emerged in Hong Kong in 1997 (HK/97 viruses), new genotypes of H5N1 viruses emerged in the same region in 2000 that were more pathogenic for both chickens and mice than HK/97 viruses. These, as well as virtually all highly pathogenic H5N1 viruses since 2000, harbour a deletion of aa 80-84 in the unstructured region of the non-structural (NS) protein NS1 linking its RNA-binding domain to its effector domain. NS segments harbouring this mutation have since been found in non-H5N1 viruses and we asked whether this 5 aa deletion could have a general effect not limited to the NS1 of H5N1 viruses. We genetically engineered this deletion in the NS segment of a duck-origin avian H1N1 virus, and compared the in vivo and in vitro properties of the WT and NSdel8084 viruses. In experimentally infected chickens, the NSdel8084 virus showed both an increased replication potential and an increased pathogenicity. This in vivo phenotype was correlated with a higher replicative efficiency in vitro, both in embryonated eggs and in a chicken lung epithelial cell line. Our data demonstrated that the increased replicative potential conferred by this small deletion was a general feature not restricted to NS1 from H5N1 viruses and suggested that viruses acquiring this mutation may be selected positively in the future.

Asunto(s)

Subtipo H1N1 del Virus de la Influenza A/fisiología; Subtipo H1N1 del Virus de la Influenza A/patogenicidad; Proteínas no Estructurales Virales/química; Proteínas no Estructurales Virales/fisiología; Secuencia de Aminoácidos; Animales; Secuencia de Bases; Línea Celular; Embrión de Pollo; Pollos; Citocinas/genética; ADN Viral/genética; Subtipo H1N1 del Virus de la Influenza A/genética; Subtipo H5N1 del Virus de la Influenza A/química; Subtipo H5N1 del Virus de la Influenza A/genética; Subtipo H5N1 del Virus de la Influenza A/fisiología; Gripe Aviar/inmunología; Gripe Aviar/patología; Gripe Aviar/virología; Interferón Tipo I/biosíntesis; Pulmón/patología; Pulmón/virología; Ratones; Datos de Secuencia Molecular; ARN Mensajero/genética; ARN Mensajero/metabolismo; Eliminación de Secuencia; Especificidad de la Especie; Carga Viral; Proteínas no Estructurales Virales/genética; Virulencia/genética; Virulencia/fisiología; Replicación Viral/genética; Replicación Viral/fisiología

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas no Estructurales Virales / Subtipo H1N1 del Virus de la Influenza A Límite: Animals Idioma: En Revista: J Gen Virol Año: 2014 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido

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