Control of Translation by the 5′- and 3′-Terminal Regions of the Dengue Virus Genome

Chiu, Wei-Wei; Kinney, Richard M.; Dreher, Theo W.

doi:10.1128/jvi.79.13.8303-8315.2005

Cited by 101 publications

(97 citation statements)

References 50 publications

(59 reference statements)

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“…0.5 l of each reaction was visualized on a 0.5% agarose gel to verify the integrity of the RNA prior to storage or use. The plasmid encoding the rabbit ␣-globin 5Ј-and 3Ј-UTRs flanking the firefly luciferase gene (pGLGpA) (15) (kindly provided by Dr. Theo Dreher of Oregon State University) was linearized by Acc65I digestion and used for the in vitro transcription. The GLGpA RNA was used as an internal control for transfections of the WT and mutant replicons.…”

Section: In Vitro Transcription Of Rna Templatesmentioning

confidence: 99%

“…Previous studies have shown that this RNA molecule contains the essential cis-acting elements required for efficient translation (15,29,30,58) as well as negative strand RNA synthesis in vitro (10,41,54,59). MPGAfold utilizes the genetic operators of mutation, recombination, and selection in parallel on a high performance computer.…”

Section: Mpgafold Analysismentioning

confidence: 99%

“…by MPGAfold-A number of studies have indicated that secondary structures in both 5Ј-and 3Ј-terminal regions are required for efficient viral RNA translation (15,29,30,58) and viral RNA synthesis (10 -12, 16, 41). In this study, we focused on the role of 5Ј-and 3Ј-DBs and potential pseudoknot base pair interactions within the CR of DENV2 RNA in translation and replication, which is currently not understood.…”

Section: The 3ј-db Forms a Stable Secondary Structure Whereas The 5јmentioning

confidence: 99%

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Identification of Cis-Acting Elements in the 3′-Untranslated Region of the Dengue Virus Type 2 RNA That Modulate Translation and Replication

Manzano

Reichert

Polo

et al. 2011

Journal of Biological Chemistry

124

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Using the massively parallel genetic algorithm for RNA folding, we show that the core region of the 3-untranslated region of the dengue virus (DENV) RNA can form two dumbbell structures (5-and 3-DBs) of unequal frequencies of occurrence. These structures have the propensity to form two potential pseudoknots between identical five-nucleotide terminal loops 1 and 2 (TL1 and TL2) and their complementary pseudoknot motifs, PK2 and PK1. Mutagenesis using a DENV2 replicon RNA encoding the Renilla luciferase reporter indicated that all four motifs and the conserved sequence 2 (CS2) element within the 3-DB are important for replication. However, for translation, mutation of TL1 alone does not have any effect; TL2 mutation has only a modest effect in translation, but translation is reduced by ϳ60% in the TL1/TL2 double mutant, indicating that TL1 exhibits a cooperative synergy with TL2 in translation. Despite the variable contributions of individual TL and PK motifs in translation, WT levels are achieved when the complementarity between TL1/PK2 and TL2/PK1 is maintained even under conditions of inhibition of the translation initiation factor 4E function mediated by LY294002 via a noncanonical pathway. Taken together, our results indicate that the cis-acting RNA elements in the core region of DENV2 RNA that include two DB structures are required not only for RNA replication but also for optimal translation. The dengue virus (DENV)3 is a mosquito-borne flavivirus (MBFV) in the Flaviviridae family that consists of over 70 members, many of which are significant human pathogens (1). The MBFV members are classified into three subgroups: DENV, yellow fever virus, and Japanese encephalitis virus (JEV) (2, 3). The four serotypes of DENV (DENV1 to -4) cause an estimated 50 million cases of infections, with ϳ10% of those leading to severe forms of the disease, dengue hemorrhagic fever and dengue shock syndrome (4 -6).The viral genome is a single-stranded RNA of positive (ϩ) polarity containing ϳ11 kilobases (10,723 nt for DENV2 New Guinea C strain, GenBank TM accession number M29095 (7)). The 3Ј-end is non-polyadenylated, and the 5Ј-end has a type I cap structure (for a review, see Ref. 8). Flanking the single long open reading frame are the 5Ј-and 3Ј-UTRs, which contain conserved cis-acting RNA secondary structure elements required for translation and replication (9 -18). The viral RNA is translated to form a polyprotein precursor, which is processed by host and viral proteases in the endoplasmic reticulum membrane. Protein processing gives rise to three structural (C, prM, and E) and seven nonstructural (NS) proteins: NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5 in that order (for reviews, see Refs. 8,19,and 20) and references therein). According to the current model for replication, assembly of the viral replicase complex occurs in a cytoplasmic membrane organelle, followed by negative (Ϫ)-strand RNA synthesis starting at the 3Ј-end of the viral genome, resulting in a double-stranded replicative form. NS3 and NS5 are multifunctional pr...

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Section: In Vitro Transcription Of Rna Templatesmentioning

confidence: 99%

Section: Mpgafold Analysismentioning

confidence: 99%

Section: The 3ј-db Forms a Stable Secondary Structure Whereas The 5јmentioning

confidence: 99%

See 1 more Smart Citation

Identification of Cis-Acting Elements in the 3′-Untranslated Region of the Dengue Virus Type 2 RNA That Modulate Translation and Replication

Manzano

Reichert

Polo

et al. 2011

Journal of Biological Chemistry

124

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show abstract

“…15 Zika virus is a positive-sense single-stranded RNA (10794kb) virus with 2 flanking non-coding regions (5' and 3' non-coding region were typically 0.09-0.1 and 0.3-0.5 kb nucleotide long, respectively). [16][17][18] Genome of Zika has open reading frame which encoding polyprotein associated with three structural proteins, Capsid (105 amino acids), premembrane (187 amino acids) and envelope (505 amino acids) and seven nonstructural proteins, NS1 (352 amino acids), NS2A (217 amino acids), NS2B (139 amino acids), NS3 (619 amino acids), NS4A (127 amino acids), NS4B (255 amino acids) and NS5 (905 amino acids). 19 The 5' UTR (non-coding region) of Zika virus consists of two conserved structural elements such as large stem loop (SLA) and short stem loop (SLB) which are essential for viral RNA synthesis and replication.…”

Section: Introductionmentioning

confidence: 99%

“…22 Moreover, the conserved secondary stem loop, DB1/DB2 and CRE (Cis-acting replication element) take part in viral translation and replication, respectively. 18,23 Therefore, the 3' UTR in different strains of Zika virus, plays a vital role in viral multiplication and pathogenicity. 22 Growing recognition of the importance of RNA is shedding light on diseases, and on how it might be treated-particularly through a process called RNA interference (RNAi).…”

Section: Introductionmentioning

confidence: 99%

A Computational Approach to Design Potential Antiviral RNA for 3’UTR Post Transcriptional Gene Silencing of Different Strains of Zika Virus

Hashem¹,

Shuvo²,

Arifuzzaman³

2017

JYP

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Dengue Fever Viruses

Whitehorn¹

2012

Encyclopedia of Life Sciences

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Dengue viruses are the most important arboviruses causing disease in humans. Approximately 3 billion people live in areas of risk, and there are an estimated 50–100 million cases occurring each year. These estimates reflect an enormous burden of morbidity, predominantly affecting urban centres of the developing world. There is currently no specific treatment and disease control is limited to tackling the vector. Despite considerable scientific attention disease pathogenesis remains incompletely understood. A better understanding of dengue virus biology and disease pathogenesis has the potential to pave the way to successful therapeutic interventions. This article aims to review current understanding of virus and vector biology, disease pathogenesis and clinical manifestations and management. Finally the article will consider novel approaches to clinical management and disease control. Key Concepts: Dengue viruses are the most important arboviruses globally. Dengue viruses are a significant cause of morbidity, particularly in the tropics. The pathogenesis of dengue results from both virus and host factors. Clinical management is limited to parenteral fluids, occasional use of blood products and supportive care. Despite a long gestation and theoretical safety concerns a dengue vaccine may soon be a reality. Novel approaches to vector control may aid global disease control efforts.

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Control of Translation by the 5′- and 3′-Terminal Regions of the Dengue Virus Genome

Cited by 101 publications

References 50 publications

Identification of Cis-Acting Elements in the 3′-Untranslated Region of the Dengue Virus Type 2 RNA That Modulate Translation and Replication

Identification of Cis-Acting Elements in the 3′-Untranslated Region of the Dengue Virus Type 2 RNA That Modulate Translation and Replication

A Computational Approach to Design Potential Antiviral RNA for 3’UTR Post Transcriptional Gene Silencing of Different Strains of Zika Virus

Dengue Fever Viruses

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