ArticleJournal of virology2014
New insights into the nonconserved noncoding region of the subtype-determinant hemagglutinin and neuraminidase segments of influenza A viruses.
Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Mapping hemagglutinin residues driving antigenic diversity in H5Nx avian influenza viruses.Journal of virology · 2026Article
- Concentration-dependent formation of intersegment interactions in the viral inclusions of influenza A virus infected cells.iScience · 2025Article
- The 5'-end segment-specific noncoding region of influenza A virus regulates both competitive multi-segment RNA transcription and selective genome packaging during infection.Journal of virology · 2025Article
- hnRNPM regulates influenza A virus replication through distinct mechanisms in human and avian cells: implications for cross-species transmission.Journal of virology · 2025Article
- Article
- Sequential disruption of SPLASH-identified vRNA-vRNA interactions challenges their role in influenza A virus genome packaging.Nucleic acids research · 2023Article
- Revisiting influenza A virus life cycle from a perspective of genome balance.Virologica Sinica · 2023Review
- Identification of the properties of H5 influenza vaccine viruses with high hemagglutinin yields.PloS one · 2023Article
- The Hierarchical Sequence Requirements of the H1 Subtype-Specific Noncoding Regions of Influenza A Virus.Microbiology spectrum · 2022Article
- Apolipoprotein E mediates cell resistance to influenza virus infection.Science advances · 2022Article
- Interactions between Influenza A Virus Nucleoprotein and Gene Segment Untranslated Regions Facilitate Selective Modulation of Viral Gene Expression.Journal of virology · 2022Article
- Synergistic Effect between 3'-Terminal Noncoding and Adjacent Coding Regions of the Influenza A Virus Hemagglutinin Segment on Template Preference.Journal of virology · 2021Article
- Evaluation of the added value of viral genomic information for predicting severity of influenza infection.BMC infectious diseases · 2021Article
- Determination of the vRNA and cRNA promoter activity by M segment-specific non-coding nucleotides of influenza A virus.RNA biology · 2021Article
- Packaging signal of influenza A virus.Virology journal · 2021Review
- The Packaging Regions of G1-Like PB2 Gene Contribute to Improving the Survival Advantage of Genotype S H9N2 Virus in China.Frontiers in microbiology · 2021Article
- Selective flexible packaging pathways of the segmented genome of influenza A virus.Nature communications · 2020Article
- Identification of a Type-Specific Promoter Element That Differentiates between Influenza A and B Viruses.Journal of virology · 2019Article
- Article
- Competitive Cooperation of Hemagglutinin and Neuraminidase during Influenza A Virus Entry.Viruses · 2019Review
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8 authors.
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No grant is acknowledged in the PubMed record.
Abstract
unlabelledThe noncoding regions (NCRs) of the eight-segmented viral RNAs (vRNAs) of influenza A virus consist of the highly conserved promoter region and the nonconserved segment-specific NCRs at both the 3' and 5' ends. The roles of the segment-specific NCRs of the eight segments have been extensively studied. However, the diversities in the same region of the two subtype-determinant hemagglutinin (HA) and neuraminidase (NA) segments have received little attention. In this study, we bioinformatically analyzed all available NCRs of HA and NA vRNAs of influenza A viruses and found that nucleotides in the segment-specific NCRs of HA and NA vRNAs are subtype specific and vary significantly in sequence and length at both the 3' and 5' ends among different subtypes. We then systematically studied the biological significance of the HA subtype-specific NCRs (HA ssNCRs) of the common HA subtypes (H1 to H7 and H9) in the context of the WSN (H1N1) reverse genetics system. We found that the HA ssNCRs play a critical role in HA vRNA virion incorporation. Upon HA vRNA incorporation, the 3'-end HA ssNCR plays a more critical role than the 5'-end HA ssNCR, and no stringent compatibility between the two ends is required. Furthermore, our data imply that, in addition to a particular nucleotide(s), the length of the HA ssNCR is involved in regulating HA vRNA incorporation efficiency. These results provide new insights into the HA segment virion incorporation that is critical for the emergence of epidemic and pandemic influenza A virus strains. IMPORTANCE: The nonconserved noncoding regions (NCRs) of the vRNAs of influenza A virus have been extensively studied, whereas the diversities in the nonconserved NCRs of the two subtype-determinant segments hemagglutinin (HA) and neuraminidase (NA) have received little attention. In this study, we bioinformatically analyzed all available NCRs of HA and NA vRNAs and discovered that the HA and NA vRNAs contain key subtype signatures in the NCRs. Our functional studies of the HA subtype-specific NCRs (HA ssNCRs) of the common HA subtypes in the context of WSN virus (H1N1) demonstrated that the HA ssNCR modulates virus replication efficiency by influencing HA segment virion incorporation. Moreover, we revealed important features of the HA ssNCR in determining HA vRNA incorporation efficiency. These data not only show new genetic characteristics of influenza A viruses, but also provide further evidence for understanding the selective genome packaging of influenza virus required for the emergence of epidemic and pandemic influenza virus strains.
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