Genome packaging in influenza A virus

Hutchinson, Edward; Kirchbach, Johann C. von; Gog, Julia R.; Digard, Paul

doi:10.1099/vir.0.017608-0

Cited by 256 publications

(297 citation statements)

References 131 publications

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“…Local secondary RNA structures are also believed to play a role in the packaging process of the eight vRNP complexes into progeny virions. Interactions between such RNA secondary structures may mediate the interaction between the eight vRNPs, leading to the observed 7+1 arrangement of vRNPs within budding virions as visualized by EM (22)(23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of the positive-sense replicative intermediate of a negative-strand RNA virus

York

Hengrung

Vreede

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

115

129

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Negative-strand RNA viruses represent a significant class of important pathogens that cause substantial morbidity and mortality in human and animal hosts worldwide. A defining feature of these viruses is that their single-stranded RNA genomes are of opposite polarity to messenger RNA and are replicated through a positivesense intermediate. The replicative intermediate is thought to exist as a complementary ribonucleoprotein (cRNP) complex. However, isolation of such complexes from infected cells has never been accomplished. Here we report the development of an RNA-based affinity-purification strategy for the isolation of cRNPs of influenza A virus from infected cells. This technological advance enabled the structural and functional characterization of this elusive but essential component of the viral RNA replication machine. The cRNP exhibits a filamentous double-helical organization with defined termini, containing the viral RNA-dependent RNA polymerase (RdRp) at one end and a loop structure at the other end. In vitro characterization of cRNP activity yielded mechanistic insights into the workings of this RNA synthesis machine. In particular, we found that cRNPs show activity in vitro only in the presence of added RdRp. Intriguingly, a replication-inactive RdRp mutant was also able to activate cRNP-templated viral RNA synthesis. We propose a model of influenza virus genome replication that relies on the trans-activation of the cRNP-associated RdRp. The described purification strategy should be applicable to other negative-strand RNA viruses and will promote studies into their replication mechanisms.

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Section: Discussionmentioning

confidence: 99%

Isolation and characterization of the positive-sense replicative intermediate of a negative-strand RNA virus

York

Hengrung

Vreede

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

115

129

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“…The convergence of cryo-EM of viral RNPs, 34 cryo-tomography of virions 41,42 and genetic analysis of RNP packaging (reviewed in ref. 43) should provide a clearer view of the influenza genome encapsidation into infectious virus.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

The influenza virus RNA synthesis machine

et al. 2011

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“…It has previously been reported that the segmentspecific NCRs of influenza A virus play multiple roles in the virus life cycle. They not only act as cis-acting signals to regulate viral transcription, replication and protein expression (Bergmann & Muster, 1996;Park & Katze, 1995;Zheng et al, 1996), but also serve as part of the packaging signals during selective virus genome packaging (Gog et al, 2007;Hutchinson et al, 2010;Zhao et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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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Genome packaging in influenza A virus

Cited by 256 publications

References 131 publications

Isolation and characterization of the positive-sense replicative intermediate of a negative-strand RNA virus

Isolation and characterization of the positive-sense replicative intermediate of a negative-strand RNA virus

The influenza virus RNA synthesis machine

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

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