D347G in PA is critical for the pathogenicity of H9N2 avian influenza A virus in mice
In brief
PA D347G mutation makes H9N2 avian flu lethal in mice
Researchers showed that the D347G change in the viral PA protein turns a recent H9N2 chicken isolate into a deadly strain for mice, boosting polymerase activity and virus replication. This single mutation serves as a new virulence marker, suggesting that H9N2 viruses carrying D347G could pose a heightened public-health threat and merit close surveillance.
- Journal
- Virulence (Q1)
- Published
- 2 August 2026
- Study design
- Unclassified
- Evidence level
- Level 5, Expert Opinion (CEBM 5)
- Authors
- Zhehong Zhao, Ye Tian, Wenjie Jiang, Xuefeng Yin, Xinran Chu, Quan Xie, et al.
- PMID
- 42543038
- DOI
- 10.1080/21505594.2026.2711518
Why clinicians should know about it
- Picked for Microbiology (medical) (paper of the day, 3 August 2026): D347G in PA, virulence marker for H9N2
Abstract
Some subtypes of avian influenza A viruses (IAVs) have been associated with human infections (e.g. H3N8, H5Ny, H7Ny, H9N2, and H10Ny), and the ability of these viruses to cause zoonotic infections further increases the public health risk of avian IAVs. Among them, H9N2 virus is one of particular importance, both in its own right and as a contributor of internal gene segments to other emerging zoonotic avian IAVs. In recent years, an increasing number of H9N2 strains have been observed to be highly pathogenic in mice without prior adaptation. In this study, we found that a naturally occurring H9N2 isolate, A/chicken/Jiangxi/198/2019 (JX198), is lethal in mice. To investigate the molecular basis for the high virulence of JX198 in mice, a series of reassortants and mutants were generated and tested. We found that the PA, especially D347G mutation in PA, is responsible for the increased pathogenicity of JX198 in mice. Notably, D347G in PA of JX198 significantly alters the polymerase activity, vRNA production, and plaque-formation. Thus, our data demonstrate that a novel molecular marker, D347G in PA, determines the virulence of H9N2 in mice, posing a potential risk of H9N2 with D347G in PA for public health and highlighting the significance of continuing surveillance of H9N2 field strains.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.