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J Virol. 2014 Jul 23. pii: JVI.01337-14. [Epub ahead of print]
New insights into the non-conserved non-coding region of the subtype-determinant HA and NA segments of influenza A viruses.
Zhao L1, Peng Y2, Zhou K1, Cao M1, Wang J1, Wang X1, Jiang T3, Deng T4.
Author information
Abstract
The non-coding regions (NCRs) of the eight RNA segments of influenza A virus consist of the highly conserved promoter region and the non-conserved 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 HA and NA segments received little attention. In this report, 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 varied 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 those common HA subtypes (H1-H7 and H9) in the context of WSN (H1N1) reverse genetics system. We found that the HA ssNCRs play a critical role in HA vRNA virion incorporation. Upon the 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 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 non-conserved non-coding regions (NCRs) of the eight segments of influenza A virus have been extensively studied whereas the diversities in the non-conserved NCRs of the two subtype-determinant segments HA and NA received little attention. In this report, we bioinformatically analyzed all available NCRs of HA and NA vRNAs and discovered that HA and NA vRNAs contain key subtype signatures in the NCR. Our functional studies of the HA ssNCRs of those 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 to influenza A viruses, but also provide further evidence in understanding the selective genome packaging of influenza virus required for the emergence of epidemic and pandemic influenza virus strains.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25056889
[PubMed - as supplied by publisher]
New insights into the non-conserved non-coding region of the subtype-determinant HA and NA segments of influenza A viruses.
Zhao L1, Peng Y2, Zhou K1, Cao M1, Wang J1, Wang X1, Jiang T3, Deng T4.
Author information
Abstract
The non-coding regions (NCRs) of the eight RNA segments of influenza A virus consist of the highly conserved promoter region and the non-conserved 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 HA and NA segments received little attention. In this report, 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 varied 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 those common HA subtypes (H1-H7 and H9) in the context of WSN (H1N1) reverse genetics system. We found that the HA ssNCRs play a critical role in HA vRNA virion incorporation. Upon the 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 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 non-conserved non-coding regions (NCRs) of the eight segments of influenza A virus have been extensively studied whereas the diversities in the non-conserved NCRs of the two subtype-determinant segments HA and NA received little attention. In this report, we bioinformatically analyzed all available NCRs of HA and NA vRNAs and discovered that HA and NA vRNAs contain key subtype signatures in the NCR. Our functional studies of the HA ssNCRs of those 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 to influenza A viruses, but also provide further evidence in understanding the selective genome packaging of influenza virus required for the emergence of epidemic and pandemic influenza virus strains.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25056889
[PubMed - as supplied by publisher]
