Zhao X, Lin X, Li P, Chen Z, Zhang C, Manicassamy. Expanding the tolerance of segmented Influenza A Virus genome using a balance compensation strategy. PLoS Pathog. 2022 Aug 4;18(8):e1010756
Reporter viruses provide powerful tools for both basic and applied virology studies, however, the creation and exploitation of reporter influenza A viruses (IAVs) have been hindered by the limited tolerance of the segmented genome to exogenous modifications. Interestingly, our previous study has demonstrated the underlying mechanism that foreign insertions reduce the replication/transcription capacity of the modified segment, impairing the delicate balance among the multiple segments during IAV infection. In the present study, we developed a "balance compensation" strategy by incorporating additional compensatory mutations during initial construction of recombinant IAVs to expand the tolerance of IAV genome. As a proof of concept, promoter-enhancing mutations were introduced within the modified segment to rectify the segments imbalance of a reporter influenza PR8-NS-Gluc virus, while directed optimization of the recombinant IAV was successfully achieved. Further, we generated recombinant IAVs expressing a much larger firefly luciferase (Fluc) by coupling with a much stronger compensatory enhancement, and established robust Fluc-based live-imaging mouse models of IAV infection. Our strategy feasibly expands the tolerance for foreign gene insertions in the segmented IAV genome, which opens up better opportunities to develop more versatile reporter IAVs as well as live attenuated influenza virus-based vaccines for other important human pathogens.
See Also:
Latest articles in those days:
- Emergence of a genetically distinct cluster of influenza A(H3N2) viruses within subclade J.2.2 associated with hospitalization during the 2024-2025 season in Auvergne-Rh?ne-Alpes, France 13 hours ago
- Interaction between DEAD-box RNA helicase 10 and influenza PB1 polymerase selectively regulates influenza A virus replication 13 hours ago
- Genetic Diversity of Clade 2.3.4.4b H5Nx High Pathogenicity Avian Influenza Viruses Detected in Korea During the 2025-2026 Winter Season and Pathogenicity of H5N1 and H5N9 Viruses 14 hours ago
- Update and optimization of a multiplex RT-qPCR assay to overcome diagnostic failure in emerging influenza A(H3N2) subclades J.2 and K (Peru, 2024-2026) 14 hours ago
- Antigenic and structural analysis of the influenza hemagglutinin lateral patch 14 hours ago
[Go Top] [Close Window]


