Core protein-mediated 5′–3′ annealing of the West Nile virus genomic RNA in vitro

Ivanyi‐Nagy, Roland; Darlix, Jean‐Luc

doi:10.1016/j.virusres.2012.05.003

Cited by 23 publications

(23 citation statements)

References 86 publications

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“…While some of these factors were shown to be essential for the viral life cycle and/or to interact with defined elements of the genomic RNA, their precise functions remained mostly uncertain. The DV NS3 protein (35), the WNV core protein (36), and the cellular La (37) were observed to support flavivirus 5=-3= RNA interactions in a similar way, as it was observed here with AUF1 p45 (Fig. 8B).…”

Section: Discussionsupporting

confidence: 78%

“…The viral core is not essential for RNA replication (39), and recombinant La was found to inhibit RNA synthesis in the in vitro viral replicase assay (40). As neither NS3, core, nor La were indicated to operate in concert with the viral polymerase, the RNA annealing activities of these proteins were proposed to contribute to virion assembly and morphogenesis (35,36).…”

Section: Discussionmentioning

confidence: 99%

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AUF1 p45 Promotes West Nile Virus Replication by an RNA Chaperone Activity That Supports Cyclization of the Viral Genome

Friedrich

Schmidt

Geißler

et al. 2014

J Virol

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A central aspect of current virology is to define the function of cellular proteins (host factors) that support the viral multiplication process. This study aimed at characterizing cellular proteins that assist the RNA replication process of the prevalent human pathogen West Nile virus (WNV). Using in vitro and cell-based approaches, we defined the p45 isoform of AU-rich element RNA-binding protein 1 (AUF1) as a host factor that enables efficient WNV replication. It was demonstrated that AUF1 p45 has an RNA chaperone activity, which aids the structural rearrangement and cyclization of the WNV RNA that is required by the viral replicase to initiate RNA replication. The obtained data suggest the RNA chaperone activity of AUF1 p45 is an important determinant of the WNV life cycle. IMPORTANCE In this study, we identified a cellular protein, AUF1 (also known as heterogeneous ribonucleoprotein D [hnRNPD]), acting as a helper (host factor) of the multiplication process of the important human pathogen West Nile virus. Several different variants ofAUF1 exist in the cell, and one variant, AUF1 p45, was shown to support viral replication most significantly. Interestingly, we obtained a set of experimental data indicating that a main function of AUF1 p45 is to modify and thus prepare the West Nile virus genome in such a way that the viral enzyme that generates progeny genomes is empowered to do this considerably more efficiently than in the absence of the host factor. The capability of AUF1 p45 to rearrange the West Nile virus genome was thus identified to be an important aspect of a West Nile virus infection.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

AUF1 p45 Promotes West Nile Virus Replication by an RNA Chaperone Activity That Supports Cyclization of the Viral Genome

Friedrich

Schmidt

Geißler

et al. 2014

J Virol

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“…RNA chaperones promote folding of RNA molecules either by preventing their misfolding or by resolving misfolded RNA species without ATP consumption (44, 45). The RNA chaperone activity of WNV capsid was mapped to the C-terminal RNA-binding region of the protein (43) and was proposed to facilitate long-range interactions in the viral genome (46). A hallmark of active RNA chaperone domains is a high content of basic residues that are structurally flexible, a property shared among all flavivirus capsid proteins; thus, capsid proteins from other members of the genus are expected to display the same RNA remodeling capacity.…”

Section: Rna-binding and Chaperone Activity Of Capsidmentioning

confidence: 99%

Properties and Functions of the Dengue Virus Capsid Protein

2016

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Dengue virus affects hundreds of millions of people each year around the world, causing a tremendous social and economic impact on affected countries. The aim of this review is to summarize our current knowledge of the functions, structure, and interactions of the viral capsid protein. The primary role of capsid is to package the viral genome. There are two processes linked to this function: the recruitment of the viral RNA during assembly and the release of the genome during infection. Although particle assembly takes place on endoplasmic reticulum membranes, capsid localizes in nucleoli and lipid droplets. Why capsid accumulates in these locations during infection remains unknown. In this review, we describe available data and discuss new ideas on dengue virus capsid functions and interactions. We believe that a deeper understanding of how the capsid protein works during infection will create opportunities for novel antiviral strategies, which are urgently needed to control dengue virus infections. KeywordsRNA virus; flavivirus; arbovirus; dengue virus; capsid protein; viral encapsidation; viral assembly; lipid droplets DENGUE VIRUSDengue virus (DENV) is the most significant arthropod-borne viral pathogen in humans. The geographical spread and incidence of DENV infections have increased dramatically in recent years. DENV is estimated to cause around 390 million infections per year, placing over 3 billion people at risk of infection (1). In addition to the heavy burden placed on public health, DENV epidemics have a huge economic impact on affected countries.DENV is a member of the Flavivirus genus of the Flaviviridae family (2). The Flavivirus genus includes other important emerging and reemerging human pathogens such as Zika virus (ZIKV), West Nile virus (WNV), Japanese encephalitis virus ( JEV), yellow fever virus (YFV), and Saint Louis encephalitis virus (SLEV) (3). Most flaviviruses are arthropodborne; however, vertebrate-and invertebrate-specific viruses are also members of the group (for a recent review see 4). DENV cycles in nature between Aedes mosquito vectors (mainly DISCLOSURE STATEMENTThe authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this review. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptAedes albopictus and Aedes aegypti ) and humans. Four DENV serotypes (DENV1, DENV2, DENV3, and DENV4) circulate in tropical and subtropical regions of the globe (5). They differ from one another by 25-40% at the amino acid level and are further separated into genotypes. Clinical outcomes for all serotypes can be unapparent or result in a spectrum of diseases ranging from self-limited dengue fever to severe dengue, a potentially lethal hemorrhagic illness. The incidence of dengue disease is growing as the mosquito vector spreads owing to urbanization, population growth, international travel, insufficient mosquito control efforts, and global warming.Although vaccines a...

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“…The involvement of viral or cell proteins in facilitating the 3′-5′ RNA-RNA interaction has been suggested. Binding of the promiscuous RNA-binding cell protein La (Vashist, Bhullar et al 2011), the viral C protein (Ivanyi-Nagy and Darlix 2012) and the viral NS3 protein (Gebhard, Kaufman et al 2012) to both the 3′ and 5′ RNA ends of flavivirus genomes has been reported. However, unless the proteins binding to each end of the RNA can interact with each other or one protein can bind simultaneously to both the 3′ and 5′ RNAs this does not seem to be a viable mechanism.…”

Section: Cell Proteins Involvement In Facilitating the 3′-5′ Rna-rmentioning

confidence: 99%

Functions of the 3′ and 5′ genome RNA regions of members of the genus Flavivirus

Brinton

Basu

2015

Virus Research

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The positive sense genomes of members of the genus Flavivirus in the family Flaviviridae are ~11 kb nts in length and have a 5′ type I cap but no 3′ poly A. The 5′ and 3′ terminal regions contain short conserved sequences that are proposed to be repeated remnants of an ancient sequence. However, the functions of most of these conserved sequences have not yet been determined. The terminal regions of the genome also contain multiple conserved RNA structures. Functional data for many of these structures has been obtained. Three sets of complementary 3′ and 5′ terminal region sequences, some of which are located in conserved RNA structures, interact to form a panhandle structure that is required for initiation of minus strand RNA synthesis with the 5′ terminal structure functioning as the promoter. How the switch from the terminal RNA structure base pairing to the long distance RNA-RNA interaction is triggered and regulated is not well understood but evidence suggests involvement of a cell protein binding to three sites on the 3′ terminal RNA structures and a cis-acting metastable 3′ RNA element in the 3′ terminal structure. Cell proteins may also be involved in facilitating exponential replication of nascent genomic RNA within replication vesicles at later times of infection cycle. Other conserved RNA structures and/or sequences in the 5′ and 3′ terminal regions have been proposed to regulate genome translation. Additional functions of the 5′ and 3′ terminal sequences have also been reported.

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Core protein-mediated 5′–3′ annealing of the West Nile virus genomic RNA in vitro

Cited by 23 publications

References 86 publications

AUF1 p45 Promotes West Nile Virus Replication by an RNA Chaperone Activity That Supports Cyclization of the Viral Genome

AUF1 p45 Promotes West Nile Virus Replication by an RNA Chaperone Activity That Supports Cyclization of the Viral Genome

Properties and Functions of the Dengue Virus Capsid Protein

Functions of the 3′ and 5′ genome RNA regions of members of the genus Flavivirus

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