Rapid emergence of a PB2 D701N substitution during adaptation of an H9N2 avian influenza virus in mice

Yang, Fan; Zhang, Xiaodi; Liu, Fumin; Yao, Hang‐Ping; Wu, Nanping; Wu, Haibo

doi:10.1007/s00705-022-05536-1

Cited by 5 publications

(2 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Avian influenza has undergone adaptive amino acid mutations during its adaptation to mammals, leading to pathological changes in the virus [21] . For example, mutations at E627K [22] and D701N [23] in PB2 of the H9N2 viruses increase their virulence and replication capacities. Combined mutations in HA (L226Q) and PB2 (M147L, V250G, or E627K) or HA (L226Q) and M1 (R210K) significantly increase the virulence of the H9N2 chicken isolate in mice, whereas the single mutation HA L226Q only increases viral replication [24] .…”

Section: Discussionmentioning

confidence: 99%

Rapid adaptive substitution of L226Q in HA protein increases the pathogenicity of H9N2 viruses in mice

Tan,

Zhang,

et al. 2024

Infectious Medicine

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Rapid adaptive substitution of L226Q in HA protein increases the pathogenicity of H9N2 viruses in mice

Tan,

Zhang,

et al. 2024

Infectious Medicine

View full text Add to dashboard Cite

“…The whole genome analyses revealed the presence of molecular mutations in the HPAI H5N1 and H5N2 viruses, which could be associated with an increased zoonotic potential. Particularly interesting was the presence of the mammalian adaptive marker D701N found in the PB2 protein of the H5N2 virus A/chicken/Nigeria/743A_22VIR3286-80/2021; it was experimentally shown by Yang et al [ 63 ] that, in a mouse-adapted H9N2 virus, this mutation conferred a higher virulence and more efficient viral replication in mouse lungs and livers. Furthermore, the H5N1 virus A/avian/Nigeria/271PT_22VIR3286-71/2021 isolated in Kano presents K482R, which has been reported to increase the polymerase activity in mammalian cell lines [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

The Evolution of Highly Pathogenic Avian Influenza A (H5) in Poultry in Nigeria, 2021–2022

Meseko

Milani

Inuwa

et al. 2023

Viruses

View full text Add to dashboard Cite

In 2021, amidst the COVID-19 pandemic and global food insecurity, the Nigerian poultry sector was exposed to the highly pathogenic avian influenza (HPAI) virus and its economic challenges. Between 2021 and 2022, HPAI caused 467 outbreaks reported in 31 of the 37 administrative regions in Nigeria. In this study, we characterized the genomes of 97 influenza A viruses of the subtypes H5N1, H5N2, and H5N8, which were identified in different agro-ecological zones and farms during the 2021–2022 epidemic. The phylogenetic analysis of the HA genes showed a widespread distribution of the H5Nx clade 2.3.4.4b and similarity with the HPAI H5Nx viruses that have been detected in Europe since late 2020. The topology of the phylogenetic trees indicated the occurrence of several independent introductions of the virus into the country, followed by a regional evolution of the virus that was most probably linked to its persistent circulation in West African territories. Additional evidence of the evolutionary potential of the HPAI viruses circulating in this region is the identification in this study of a putative H5N1/H9N2 reassortant virus in a mixed-species commercial poultry farm. Our data confirm Nigeria as a crucial hotspot for HPAI virus introduction from the Eurasian territories and reveal a dynamic pattern of avian influenza virus evolution within the Nigerian poultry population.

show abstract

Mammalian adaptation risk in HPAI H5N8: a comprehensive model bridging experimental data with mathematical insights

Chokkakula,

Oh,

Choi

et al. 2024

Emerging Microbes & Infections

View full text Add to dashboard Cite

Understanding the mammalian pathogenesis and interspecies transmission of HPAI H5N8 virus hinges on mapping its adaptive markers. We used deep sequencing to track these markers over five passages in murine lung tissue. Subsequently, we evaluated the growth, selection, and RNA load of eight recombinant viruses with mammalian adaptive markers. By leveraging an integrated non-linear regression model, we quantitatively determined the influence of these markers on growth, adaptation, and RNA expression in mammalian hosts. Furthermore, our findings revealed that the interplay of these markers can lead to synergistic, additive, or antagonistic effects when combined. The elucidation distance method then transformed these results into distinct values, facilitating the derivation of a risk score for each marker. In vivo tests affirmed the accuracy of scores. As more mutations were incorporated, the overall risk score of virus heightened, and the optimal interplay between markers became essential for risk augmentation. Our study provides a robust model to assess risk from adaptive markers of HPAI H5N8, guiding strategies against future influenza threats.

show abstract

Rapid emergence of a PB2 D701N substitution during adaptation of an H9N2 avian influenza virus in mice

Cited by 5 publications

References 34 publications

Rapid adaptive substitution of L226Q in HA protein increases the pathogenicity of H9N2 viruses in mice

Rapid adaptive substitution of L226Q in HA protein increases the pathogenicity of H9N2 viruses in mice

The Evolution of Highly Pathogenic Avian Influenza A (H5) in Poultry in Nigeria, 2021–2022

Mammalian adaptation risk in HPAI H5N8: a comprehensive model bridging experimental data with mathematical insights

Contact Info

Product

Resources

About