Amino acid mutations PB1-V719M and PA-N444D combined with PB2-627K contribute to the pathogenicity of H7N9 in mice
Rattachement africain : cn, mv. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
H7N9 subtype avian influenza viruses (AIVs) cause 1567 human infections and have high mortality, posing a significant threat to public health. Previously, we reported that two avian-derived H7N9 isolates (A/chicken/Eastern China/JTC4/2013 and A/chicken/Eastern China/JTC11/2013) exhibit different pathogenicities in mice. To understand the genetic basis for the differences in virulence, we constructed a series of mutant viruses based on reverse genetics. We found that the PB2-E627K mutation alone was not sufficient to increase the virulence of H7N9 in mice, despite its ability to enhance polymerase activity in mammalian cells. However, combinations with PB1-V719M and/or PA-N444D mutations significantly enhanced H7N9 virulence. Additionally, these combined mutations augmented polymerase activity, thereby intensifying virus replication, inflammatory cytokine expression, and lung injury, ultimately increasing pathogenicity in mice. Overall, this study revealed that virulence in H7N9 is a polygenic trait and identified novel virulence-related residues (PB2-627K combined with PB1-719M and/or PA-444D) in viral ribonucleoprotein (vRNP) complexes. These findings provide new insights into the molecular mechanisms underlying AIV pathogenesis in mammals, with implications for pandemic preparedness and intervention strategies.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Amino acid mutations PB1-V719M and PA-N444D combined with PB2-627K contribute to the pathogenicity of H7N9 in mice
- Date Crossref
- 05/07/2024
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Yangzhou University Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis pays non établi dans la noticeUniversité ou école supérieure
-
Ministry of Education pays non établi dans la noticeOrganisme public
-
College of Veterinary Medicine pays non établi dans la noticeUniversité ou école supérieure
-
Jiangsu Key Laboratory of Zoonosis pays non établi dans la noticeStructure de recherche
-
Yangzhou Center for Disease Control and Prevention pays non établi dans la noticeInstitution
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis — Yangzhou University, Ministry of Education et College of Veterinary Medicine, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.