Complete Genome Sequence of a Mammalian Species-Infectious and -Pathogenic H6N5 Avian Influenza Virus without Evidence of Adaptation

Park, Seongjun; Park, Bong‐Kyun; Song, Daesub; Poo, Haryoung

doi:10.1128/jvi.02301-12

Cited by 11 publications

(4 citation statements)

References 20 publications

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“…While the lengths of the 3′ and 5′ NCRs of the viral RNA of A/feline/Korea/01/2010 (H3N2) were variable (19 to 45 and 20 to 58 nt at the 3′ and 5′ NCRs, respectively) in the different genome segments, the terminal 12 and 13 nt of the 3′ and 5′ ends, respectively, were highly conserved (3′-UCGYUUUCGUCC- and -GGAACAAAGAUGA-5′) among all eight genome segments, which is consistent with previous studies (13, 14, 19, 20). Surprisingly, 1 nt was changed between the start codon (UAC) and the conserved region (UCGYUUUCGUCC) in the 3′ NCR of Seg-1 and also in Seg-6 of A/feline/Korea/01/2010 (H3N2) compared to A/canine/Korea/01/2007 (H3N2).…”

Section: Genome Announcementsupporting

confidence: 90%

Complete Genome Sequence of a Canine-Origin H3N2 Feline Influenza Virus Isolated from Domestic Cats in South Korea

et al. 2013

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Section: Genome Announcementsupporting

confidence: 90%

Complete Genome Sequence of a Canine-Origin H3N2 Feline Influenza Virus Isolated from Domestic Cats in South Korea

et al. 2013

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“…1A and B). To validate these HA and NA ssNCR sequence logos, we also examined the NCR sequences from the literature, which were determined accurately by specific NCRsequencing methods (27,(32)(33)(34)(35)(36), and compared them with the sequence logos generated from the bioinformatics analysis (Fig. 1C).…”

Section: Resultsmentioning

confidence: 99%

New Insights into the Nonconserved Noncoding Region of the Subtype-Determinant Hemagglutinin and Neuraminidase Segments of Influenza A Viruses

Zhao

Peng

Zhou

et al. 2014

J Virol

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The 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. IMPORTANCEThe 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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“…It can be seen that, within each segment-specific NCR, most nucleotides are highly conserved, whereas, at certain nucleotide positions, the identities of nucleotides are variable (most of them are transition changes). We further validated these sequence logos by comparing them with the NCR sequence logos determined by accurate NCR sequencing methods (Park et al, 2013(Park et al, , 2012Su et al, 2012;Wang & Lee, 2009;. We found that the majority of nucleotide conservation/variation at each nucleotide position was generally consistent between the sequence logos (Fig.…”

Section: Bioinformatics Analysis Of the Segment-specific Non-coding Rmentioning

confidence: 83%

Influenza A virus utilizes a suboptimal Kozak sequence to fine-tune virus replication and host response

Wang

Peng

Zhao

et al. 2015

Journal of General Virology

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The segment-specific non-coding regions (NCRs) of influenza A virus RNA genome play important roles in controlling viral RNA transcription, replication and genome packaging. In this report, we present, for the first time to our knowledge, a full view of the segment-specific NCRs of all influenza A viruses by bioinformatics analysis. Our systematic functional analysis revealed that the eight segment-specific NCRs identified could differentially regulate viral RNA synthesis and protein expression at both transcription and translation levels. Interestingly, a highly conserved suboptimal nucleotide at "3 position of the Kozak sequence, which downregulated protein expression at the translation level, was only present in the segment-specific NCR of PB1. By reverse genetics, we demonstrate that recombinant viruses with an optimized Kozak sequence at the "3 position in PB1 resulted in a significant multiple-cycle replication reduction that was independent of PB1-F2 expression. Our detailed dynamic analysis of virus infection revealed that the mutant virus displays slightly altered dynamics from the wild-type virus on both viral RNA synthesis and protein production. Furthermore, we demonstrated that the level of PB1 expression is involved in regulating type I IFN production. Together, these data reveal a novel strategy exploited by influenza A virus to fine-tune virus replication dynamics and host antiviral response through regulating PB1 protein expression.

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Complete Genome Sequence of a Mammalian Species-Infectious and -Pathogenic H6N5 Avian Influenza Virus without Evidence of Adaptation

Cited by 11 publications

References 20 publications

Complete Genome Sequence of a Canine-Origin H3N2 Feline Influenza Virus Isolated from Domestic Cats in South Korea

Complete Genome Sequence of a Canine-Origin H3N2 Feline Influenza Virus Isolated from Domestic Cats in South Korea

New Insights into the Nonconserved Noncoding Region of the Subtype-Determinant Hemagglutinin and Neuraminidase Segments of Influenza A Viruses

Influenza A virus utilizes a suboptimal Kozak sequence to fine-tune virus replication and host response

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