ArticleJournal of virology2017
Dual Roles of the Hemagglutinin Segment-Specific Noncoding Nucleotides in the Extended Duplex Region of the Influenza A Virus RNA Promoter.
Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- 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
- Expanding the tolerance of segmented Influenza A Virus genome using a balance compensation strategy.PLoS pathogens · 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
- Determination of the vRNA and cRNA promoter activity by M segment-specific non-coding nucleotides of influenza A virus.RNA biology · 2021Article
- Organization of the Influenza A Virus Genomic RNA in the Viral Replication Cycle-Structure, Interactions, and Implications for the Emergence of New Strains.Pathogens (Basel, Switzerland) · 2020Review
- Competitive Cooperation of Hemagglutinin and Neuraminidase during Influenza A Virus Entry.Viruses · 2019Review
- Structural and Functional Motifs in Influenza Virus RNAs.Frontiers in microbiology · 2018Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We recently reported that the segment-specific noncoding regions (NCRs) of the hemagglutinin (HA) and neuraminidase (NA) segments are subtype specific, varying significantly in sequence and length at both the 3' and 5' ends. Interestingly, we found that nucleotides CC at positions 13 and 14 at the 3' end and GUG at positions 14 to 16 at the 5' end (termed 14' and 16' to distinguish them from 3' positions) are absolutely conserved among all HA subtype-specific NCRs. These HA segment-specific NCR nucleotides are located in the extended duplex region of the viral RNA promoter. In order to understand the significance of these highly conserved HA segment-specific NCR nucleotides in the virus life cycle, we performed extensive mutagenesis on the HA segment-specific NCR nucleotides and studied their functional significance in regulating influenza A virus replication in the context of the HA segment with both RNP reconstitution and virus infection systems. We found that the base pairing of the 3'-end 13 position with the 5'-end 14' position ( IMPORTANCE: The segment-specific complementary nucleotides (13 to 15 in the 3' end and 14' to 16' in the 5' end) in the extended duplex region of the influenza virus RNA promoter vary significantly among different segments and have rarely been studied. Here, we performed mutagenesis analysis of the highly conserved HA segment-specific nucleotides in the extended duplex region and examined their effects on virus replication in the context of the influenza A/WSN/33 (WSN) virus infection. We found that these HA segment-specific nucleotides not only act as a part of the RNA promoter but also play a critical role in HA segment packaging. Therefore, we showed experimentally, for the first time, the requirement of the nucleotides in the extended duplex region for the RNA promoter and also identified specific noncoding residues in regulating HA segment packaging. This work has implications for the development of attenuated vaccine strains and for elucidation the mechanisms of the virus genome packaging.
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