tetano
Editor, Senior Moderator
Biochem Biophys Res Commun
. 2025 Dec 3:795:153082.
doi: 10.1016/j.bbrc.2025.153082. Online ahead of print. Disruption of the local vRNA structure at the end of HA encoding region interferes with the selective packaging of influenza A virus genome
Jing Hu[SUP] 1 [/SUP], Jianchao Li[SUP] 1 [/SUP], Wanling You[SUP] 2 [/SUP], Long Liu[SUP] 3 [/SUP], Hongying Chen[SUP] 4 [/SUP]
Affiliations
Influenza A virus (IAV) selectively packages eight distinct viral RNA (vRNA) segments into progeny virions through segment-specific packaging signals located in the noncoding regions and their adjacent coding sequences. Emerging evidence indicates that local secondary structures within these regions are involved in intersegment RNA-RNA interactions required for selective genome incorporation. Here, we examined a structured motif in the 3' coding region of the WSN HA vRNA by introducing synonymous mutations at two cytidines (C1720 and C1726), which were predicted to convert an intrinsic bulge into a stem-loop structure. Although viral protein expression and hemagglutination activity remained comparable to the wild type virus, the mutant virus (WSN-vHA) displayed reduced plaque size, decreased viral titer and a significantly lower PFU/HA ratio. Quantification of vRNAs in released viral particles showed disrupted stoichiometry of segment assembly, and electron microscopy confirmed the presence of empty or vRNP-deficient particles. WSN-vHA also exhibited significantly attenuated replication and pathogenicity in mice. Together, these findings identified two critical nucleotide sites in the WSN HA segment for selective genome incorporation and virion assembly, highlighting the importance of local RNA structural integrity in IAV replication and virulence.
Keywords: Defective interfering particles; Genome packaging; Influenza A virus; RNA secondary structure.
. 2025 Dec 3:795:153082.
doi: 10.1016/j.bbrc.2025.153082. Online ahead of print. Disruption of the local vRNA structure at the end of HA encoding region interferes with the selective packaging of influenza A virus genome
Jing Hu[SUP] 1 [/SUP], Jianchao Li[SUP] 1 [/SUP], Wanling You[SUP] 2 [/SUP], Long Liu[SUP] 3 [/SUP], Hongying Chen[SUP] 4 [/SUP]
Affiliations
- PMID: 41351899
- DOI: 10.1016/j.bbrc.2025.153082
Influenza A virus (IAV) selectively packages eight distinct viral RNA (vRNA) segments into progeny virions through segment-specific packaging signals located in the noncoding regions and their adjacent coding sequences. Emerging evidence indicates that local secondary structures within these regions are involved in intersegment RNA-RNA interactions required for selective genome incorporation. Here, we examined a structured motif in the 3' coding region of the WSN HA vRNA by introducing synonymous mutations at two cytidines (C1720 and C1726), which were predicted to convert an intrinsic bulge into a stem-loop structure. Although viral protein expression and hemagglutination activity remained comparable to the wild type virus, the mutant virus (WSN-vHA) displayed reduced plaque size, decreased viral titer and a significantly lower PFU/HA ratio. Quantification of vRNAs in released viral particles showed disrupted stoichiometry of segment assembly, and electron microscopy confirmed the presence of empty or vRNP-deficient particles. WSN-vHA also exhibited significantly attenuated replication and pathogenicity in mice. Together, these findings identified two critical nucleotide sites in the WSN HA segment for selective genome incorporation and virion assembly, highlighting the importance of local RNA structural integrity in IAV replication and virulence.
Keywords: Defective interfering particles; Genome packaging; Influenza A virus; RNA secondary structure.