To explore adaptation of avian influenza virus to mice we previously performed serial lung-to-lung passages of the influenza A/Chicken/Jiangsu/7/2002 (H9N2) strain, resulting in the isolation of a variant influenza strain lethal for mice. We now report that virulence correlates with improved growth characteristics on mammalian cells and extended tissue tropism in vivo. Sequencing of the complete genomes of the wild-type and mouse-adapted viruses revealed 25 amino acid substitutions. Some were found to reiterate known substitutions in human and swine H9N2 influenza isolates. Functions affected include nuclear localization signals and sites of protein and RNA interaction, while others are known determinants of pathogenicity and host specificity such as the viral polymerase PB2 E627K substitution. These observations suggest that enhanced growth characteristics and modified cell tropism may contribute to increased virulence in mice. We conclude that multiple amino acid substitutions are likely to be involved in the adaptation of H9N2 avian influenza virus to mice. 相似文献
1. The aim of this study was to describe the role of Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) receptor signalling in chicken.
2. Tissue-specific expression analysis of NOD1, receptor-interacting serine-threonine kinase 2 (RIPK2), nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase 11 (MAPK11 or p38) by quantitative real-time PCR (qRT-PCR) revealed their wide distribution in various organs and tissues.
3. Salmonella pullorum infection activated NOD1 receptor signalling in vivo and in vitro, resulting in significant induction of downstream signalling molecules RIPK2, NF-κB/p65, MAPK11/p38 and the effector molecules IL-1b and IL-8.
4. Activation of NOD1 by its agonist bacterial γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP) in HD11 cells induced the adapter molecular RIPK2 and activated the NF-κB/p65 and MAPK11/p38 pathways, resulting in an increase in IL-8 but not IL-1β. Additionally, inhibition of NOD1 using NOD1-shRNA resulted in downregulation of RIPK2, MAPK11 and IL-8, while NF-κB/p65 and IL-1β were unaltered.
5. These results highlight the important role of NOD1 receptors in eliciting the innate immune response following pathogenic invasion in chicken. 相似文献