tetano
Editor, Senior Moderator
J Gen Virol. 2014 Dec 17. pii: vir.0.000030. doi: 10.1099/vir.0.000030. [Epub ahead of print]
[h=1]Influenza A virus Utilizes a Suboptimal Kozak Sequence to Fine-tune Virus Replication and Host Response.[/h] Wang J[SUP]1[/SUP], Peng Y[SUP]2[/SUP], Zhao L[SUP]1[/SUP], Cao M[SUP]1[/SUP], Hung T[SUP]1[/SUP], Deng T[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 reveal that the eight segment-specific NCRs could differently regulate viral RNA synthesis and protein expression at both transcription and translation levels. Interestingly, a highly conserved suboptimal nucleotide at -3 position of Kozak sequence, that could down-regulate protein expression at translation level, is only present in the segment-specific NCR of PB1. By reverse genetics, we demonstrate that recombinant viruses with an optimized Kozak sequence at -3 position in PB1 results in a significant multiple-cycle replication reduction that is independent of PB1-F2 expression. Our detailed dynamic analysis of the virus infection reveals that, the mutant virus displays slightly altered dynamics from the wild type virus on both viral RNA synthesis and protein production. Furthermore, we demonstrate that the level of PB1 expression is involved in regulating type I interferon production. Together, these data reveal a novel strategy exploited by influenza A virus to fine-tune virus replication dynamics and host anti-viral response through regulating PB1 protein expression.
PMID: 25519170 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25519170
[h=1]Influenza A virus Utilizes a Suboptimal Kozak Sequence to Fine-tune Virus Replication and Host Response.[/h] Wang J[SUP]1[/SUP], Peng Y[SUP]2[/SUP], Zhao L[SUP]1[/SUP], Cao M[SUP]1[/SUP], Hung T[SUP]1[/SUP], Deng T[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 reveal that the eight segment-specific NCRs could differently regulate viral RNA synthesis and protein expression at both transcription and translation levels. Interestingly, a highly conserved suboptimal nucleotide at -3 position of Kozak sequence, that could down-regulate protein expression at translation level, is only present in the segment-specific NCR of PB1. By reverse genetics, we demonstrate that recombinant viruses with an optimized Kozak sequence at -3 position in PB1 results in a significant multiple-cycle replication reduction that is independent of PB1-F2 expression. Our detailed dynamic analysis of the virus infection reveals that, the mutant virus displays slightly altered dynamics from the wild type virus on both viral RNA synthesis and protein production. Furthermore, we demonstrate that the level of PB1 expression is involved in regulating type I interferon production. Together, these data reveal a novel strategy exploited by influenza A virus to fine-tune virus replication dynamics and host anti-viral response through regulating PB1 protein expression.
PMID: 25519170 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25519170