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1.
Virus Res ; 179: 64-72, 2014 Jan 22.
Article de Anglais | MEDLINE | ID: mdl-24269912

RÉSUMÉ

While the effect of the influenza A virus non-structural protein (NS) on cytokine production during viral infection is well known, inconsistent results have been observed with some other influenza A virus backbone studied. In this study, in order to focus on the impact of the avian NS gene segments on viral virulence, the NS genes encoded by different strains of avian influenza A viruses were incorporated into an identical [A/Puerto Rico/8/1934(H1N1), PR8] virus background to generate various NS recombinant viruses. Thus, PR8NS, PR8×[A/Hong Kong/483/97(H5N1) 483NS, PR8×[A/Ck/Korea/150/03(H9N2) 150NS, and PR8×[A/EM/Korea/W149/06(H5N1) W149NS were constructed utilizing reverse genetics. Here, we show the effects of each of these recombinant viruses upon viral pathogenesis and cytokine production during viral replication in vivo. In this regard, we found that infection of mice with the PR8×150NS recombinant virus resulted in the lowest pathogenicity (6.0×10(4)MLD50), yet elicited the highest levels of TNF-α production in bronchoalveolar lavage (BAL) fluid compared to infection with the other recombinant influenza viruses. In contrast, infection with the PR8 virus showed the highest pathogenicity (1.0×10(2)MLD50) as well as relatively high cytokine levels (IL-1α, IL-1ß, IL-17, and eotaxin) in mouse BAL fluid. In addition, the PR8 and PR8×483NS viruses induced severe and extensive inflammation in infected lungs compared with that of PR8×150 NS recombinant virus-infected mice. These results clearly demonstrate that the NS genes of diverse influenza A strains can variable impact pathogenicity, histopathology, and cytokine production in mice even when expressed in an identical genetic background.


Sujet(s)
Sous-type H1N1 du virus de la grippe A/pathogénicité , Grippe humaine/virologie , Protéines virales non structurales/métabolisme , Animaux , Oiseaux , Poulets , Femelle , Humains , Sous-type H1N1 du virus de la grippe A/génétique , Sous-type H1N1 du virus de la grippe A/métabolisme , Sous-type H5N1 du virus de la grippe A/génétique , Sous-type H5N1 du virus de la grippe A/métabolisme , Sous-type H5N1 du virus de la grippe A/pathogénicité , Sous-type H9N2 du virus de la grippe A/génétique , Sous-type H9N2 du virus de la grippe A/métabolisme , Sous-type H9N2 du virus de la grippe A/pathogénicité , Virus de la grippe A/génétique , Virus de la grippe A/métabolisme , Virus de la grippe A/pathogénicité , Grippe chez les oiseaux/virologie , Grippe humaine/immunologie , Souris , Recombinaison génétique , Protéines virales non structurales/génétique , Virulence
2.
Nat Genet ; 42(4): 322-7, 2010 Apr.
Article de Anglais | MEDLINE | ID: mdl-20305664

RÉSUMÉ

Breeding to increase beta-carotene levels in cereal grains, termed provitamin A biofortification, is an economical approach to address dietary vitamin A deficiency in the developing world. Experimental evidence from association and linkage populations in maize (Zea mays L.) demonstrate that the gene encoding beta-carotene hydroxylase 1 (crtRB1) underlies a principal quantitative trait locus associated with beta-carotene concentration and conversion in maize kernels. crtRB1 alleles associated with reduced transcript expression correlate with higher beta-carotene concentrations. Genetic variation at crtRB1 also affects hydroxylation efficiency among encoded allozymes, as observed by resultant carotenoid profiles in recombinant expression assays. The most favorable crtRB1 alleles, rare in frequency and unique to temperate germplasm, are being introgressed via inexpensive PCR marker-assisted selection into tropical maize germplasm adapted to developing countries, where it is most needed for human health.


Sujet(s)
Polymorphisme génétique , Zea mays/génétique , Bêtacarotène/métabolisme , Grains comestibles/métabolisme , Expression des gènes , Gènes de plante , Mixed function oxygenases/génétique , Données de séquences moléculaires , Locus de caractère quantitatif
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