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1

Alcaraz-Estrada, Sofia Lizeth, Martha Yocupicio-Monroy, and Rosa María del Angel. "Insights into dengue virus genome replication." Future Virology 5, no. 5 (2010): 575–92. http://dx.doi.org/10.2217/fvl.10.49.

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2

Wang, Kezhen, Juanjuan Wang, Ta Sun, et al. "Glycosphingolipid GM3 is Indispensable for Dengue Virus Genome Replication." International Journal of Biological Sciences 12, no. 7 (2016): 872–83. http://dx.doi.org/10.7150/ijbs.15641.

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3

Alvarez, Diego E., María F. Lodeiro, Silvio J. Ludueña, Lía I. Pietrasanta, and Andrea V. Gamarnik. "Long-Range RNA-RNA Interactions Circularize the Dengue Virus Genome." Journal of Virology 79, no. 11 (2005): 6631–43. http://dx.doi.org/10.1128/jvi.79.11.6631-6643.2005.

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ABSTRACT Secondary and tertiary RNA structures present in viral RNA genomes play essential regulatory roles during translation, RNA replication, and assembly of new viral particles. In the case of flaviviruses, RNA-RNA interactions between the 5′ and 3′ ends of the genome have been proposed to be required for RNA replication. We found that two RNA elements present at the ends of the dengue virus genome interact in vitro with high affinity. Visualization of individual molecules by atomic force microscopy reveled that physical interaction between these RNA elements results in cyclization of the
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4

Yamamoto, Kristie A., Kevin Blackburn, Michael B. Goshe, et al. "Tizoxanide Antiviral Activity on Dengue Virus Replication." Viruses 15, no. 3 (2023): 696. http://dx.doi.org/10.3390/v15030696.

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Dengue virus is an important circulating arbovirus in Brazil responsible for high morbidity and mortality worldwide, representing a huge economic and social burden, in addition to affecting public health. In this study, the biological activity, toxicity, and antiviral activity against dengue virus type 2 (DENV-2) of tizoxanide (TIZ) was evaluated in Vero cell culture. TIZ has a broad spectrum of action in inhibiting different pathogens, including bacteria, protozoa, and viruses. Cells were infected for 1 h with DENV-2 and then treated for 24 h with different concentrations of the drug. The qua
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5

Leitmeyer, Katrin C., David W. Vaughn, Douglas M. Watts, et al. "Dengue Virus Structural Differences That Correlate with Pathogenesis." Journal of Virology 73, no. 6 (1999): 4738–47. http://dx.doi.org/10.1128/jvi.73.6.4738-4747.1999.

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ABSTRACT The understanding of dengue virus pathogenesis has been hampered by the lack of in vitro and in vivo models of disease. The study of viral factors involved in the production of severe dengue, dengue hemorrhagic fever (DHF), versus the more common dengue fever (DF), have been limited to indirect clinical and epidemiologic associations. In an effort to identify viral determinants of DHF, we have developed a method for comparing dengue type 2 genomes (reverse transcriptase PCR in six fragments) directly from patient plasma. Samples for comparison were selected from two previously describ
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Dethoff, Elizabeth A., Mark A. Boerneke, Nandan S. Gokhale, et al. "Pervasive tertiary structure in the dengue virus RNA genome." Proceedings of the National Academy of Sciences 115, no. 45 (2018): 11513–18. http://dx.doi.org/10.1073/pnas.1716689115.

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RNA virus genomes are efficient and compact carriers of biological information, encoding information required for replication both in their primary sequences and in higher-order RNA structures. However, the ubiquity of RNA elements with higher-order folds—in which helices pack together to form complex 3D structures—and the extent to which these elements affect viral fitness are largely unknown. Here we used single-molecule correlated chemical probing to define secondary and tertiary structures across the RNA genome of dengue virus serotype 2 (DENV2). Higher-order RNA structures are pervasive a
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Asyura, Muhammad Mikail Athif Zhafir, Ahmad Fauzi, and Fakhru Adlan Ayub. "Potential of Peptide-Based Non-Structural Protein 1 (NS1) Inhibitor in Obstructing Dengue Virus (DENV) Replication." Green Medical Journal 3, no. 1 (2021): 1–12. http://dx.doi.org/10.33096/gmj.v3i1.71.

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Introduction: Dengue Virus (DENV) is the pathogen for human dengue fever and is responsible for 390 million infections per year. The viral genome produces about 10 viral protein products, one of them being NS1. The NS1 protein plays a key role in viral replication and stimulation of humoral immune cells, thus being the perfect candidate to create an effective antiviral drug or vaccine for dengue
 Methods: Dengue Virus (DENV) is the pathogen for human dengue fever and is responsible for 390 million infections per year. The viral genome produces about 10 viral protein products, one of them
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8

Yang, Siwy Ling, Riccardo Delli Ponti, Yue Wan, and Roland G. Huber. "Computational and Experimental Approaches to Study the RNA Secondary Structures of RNA Viruses." Viruses 14, no. 8 (2022): 1795. http://dx.doi.org/10.3390/v14081795.

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Most pandemics of recent decades can be traced to RNA viruses, including HIV, SARS, influenza, dengue, Zika, and SARS-CoV-2. These RNA viruses impose considerable social and economic burdens on our society, resulting in a high number of deaths and high treatment costs. As these RNA viruses utilize an RNA genome, which is important for different stages of the viral life cycle, including replication, translation, and packaging, studying how the genome folds is important to understand virus function. In this review, we summarize recent advances in computational and high-throughput RNA structure-m
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9

Markoff, Lewis, Xiaou Pang, Huo-shu Houng, et al. "Derivation and Characterization of a Dengue Type 1 Host Range-Restricted Mutant Virus That Is Attenuated and Highly Immunogenic in Monkeys." Journal of Virology 76, no. 7 (2002): 3318–28. http://dx.doi.org/10.1128/jvi.76.7.3318-3328.2002.

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ABSTRACT We recently described the derivation of a dengue serotype 2 virus (DEN2mutF) that exhibited a host range-restricted phenotype; it was severely impaired for replication in cultured mosquito cells (C6/36 cells). DEN2mutF virus had selected mutations in genomic sequences predicted to form a 3′ stem-loop structure (3′-SL) that is conserved among all flavivirus species. The 3′-SL constitutes the downstream terminal ∼95 nucleotides of the 3′ noncoding region in flavivirus RNA. Here we report the introduction of these same mutational changes into the analogous region of an infectious DNA der
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10

Sanford, Thomas J., Harriet V. Mears, Teodoro Fajardo, Nicolas Locker, and Trevor R. Sweeney. "Circularization of flavivirus genomic RNA inhibits de novo translation initiation." Nucleic Acids Research 47, no. 18 (2019): 9789–802. http://dx.doi.org/10.1093/nar/gkz686.

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Abstract Members of the Flaviviridae family, including dengue virus (DENV) and yellow fever virus, cause serious disease in humans, whilst maternal infection with Zika virus (ZIKV) can induce microcephaly in newborns. Following infection, flaviviral RNA genomes are translated to produce the viral replication machinery but must then serve as a template for the transcription of new genomes. However, the ribosome and viral polymerase proceed in opposite directions along the RNA, risking collisions and abortive replication. Whilst generally linear, flavivirus genomes can adopt a circular conformat
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11

Fajardo, Teodoro, Thomas J. Sanford, Harriet V. Mears, et al. "The flavivirus polymerase NS5 regulates translation of viral genomic RNA." Nucleic Acids Research 48, no. 9 (2020): 5081–93. http://dx.doi.org/10.1093/nar/gkaa242.

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Abstract Flaviviruses, including dengue virus and Zika virus, contain a single-stranded positive sense RNA genome that encodes viral proteins essential for replication and also serves as the template for new genome synthesis. As these processes move in opposite directions along the genome, translation must be inhibited at a defined point following infection to clear the template of ribosomes to allow efficient replication. Here, we demonstrate in vitro and in cell-based assays that the viral RNA polymerase, NS5, inhibits translation of the viral genome. By reconstituting translation in vitro u
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12

Pugachev, Konstantin V., Farshad Guirakhoo, Simeon W. Ocran, et al. "High Fidelity of Yellow Fever Virus RNA Polymerase." Journal of Virology 78, no. 2 (2004): 1032–38. http://dx.doi.org/10.1128/jvi.78.2.1032-1038.2004.

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ABSTRACT Three consecutive plaque purifications of four chimeric yellow fever virus-dengue virus (ChimeriVax-DEN) vaccine candidates against dengue virus types 1 to 4 were performed. The genome of each candidate was sequenced by the consensus approach after plaque purification and additional passages in cell culture. Our data suggest that the nucleotide sequence error rate for SP6 RNA polymerase used in the in vitro transcription step to initiate virus replication was as high as 1.34 × 10−4 per copied nucleotide and that the error rate of the yellow fever virus RNA polymerase employed by the c
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13

Butler, Molly, Nunya Chotiwan, Connie D. Brewster, et al. "Cyclin-Dependent Kinases 8 and 19 Regulate Host Cell Metabolism during Dengue Virus Serotype 2 Infection." Viruses 12, no. 6 (2020): 654. http://dx.doi.org/10.3390/v12060654.

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Dengue virus infection is associated with the upregulation of metabolic pathways within infected cells. This effect is common to infection by a broad array of viruses. These metabolic changes, including increased glucose metabolism, oxidative phosphorylation and autophagy, support the demands of viral genome replication and infectious particle formation. The mechanisms by which these changes occur are known to be, in part, directed by viral nonstructural proteins that contact and control cellular structures and metabolic enzymes. We investigated the roles of host proteins with overarching cont
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14

Choi, Kyung H. "The Role of the Stem-Loop A RNA Promoter in Flavivirus Replication." Viruses 13, no. 6 (2021): 1107. http://dx.doi.org/10.3390/v13061107.

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An essential challenge in the lifecycle of RNA viruses is identifying and replicating the viral genome amongst all the RNAs present in the host cell cytoplasm. Yet, how the viral polymerase selectively recognizes and copies the viral RNA genome is poorly understood. In flaviviruses, the 5′-end of the viral RNA genome contains a 70 nucleotide-long stem-loop, called stem-loop A (SLA), which functions as a promoter for genome replication. During replication, flaviviral polymerase NS5 specifically recognizes SLA to both initiate viral RNA synthesis and to methylate the 5′ guanine cap of the nascen
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15

Lodeiro, María F., Claudia V. Filomatori, and Andrea V. Gamarnik. "Structural and Functional Studies of the Promoter Element for Dengue Virus RNA Replication." Journal of Virology 83, no. 2 (2008): 993–1008. http://dx.doi.org/10.1128/jvi.01647-08.

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ABSTRACT The 5′ untranslated region (5′UTR) of the dengue virus (DENV) genome contains two defined elements essential for viral replication. At the 5′ end, a large stem-loop (SLA) structure functions as the promoter for viral polymerase activity. Next to the SLA, there is a short stem-loop that contains a cyclization sequence known as the 5′ upstream AUG region (5′UAR). Here, we analyzed the secondary structure of the SLA in solution and the structural requirements of this element for viral replication. Using infectious DENV clones, viral replicons, and in vitro polymerase assays, we defined t
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García-Ariza, Leidy Lorena, Natalia González-Rivillas, Cindy Johanna Díaz-Aguirre, Cristian Rocha-Roa, Leonardo Padilla-Sanabria, and Jhon Carlos Castaño-Osorio. "Antiviral Activity of an Indole-Type Compound Derived from Natural Products, Identified by Virtual Screening by Interaction on Dengue Virus NS5 Protein." Viruses 15, no. 7 (2023): 1563. http://dx.doi.org/10.3390/v15071563.

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Dengue is an acute febrile illness caused by the Dengue virus (DENV), with a high number of cases worldwide. There is no available treatment that directly affects the virus or the viral cycle. The objective of this study was to identify a compound derived from natural products that interacts with the NS5 protein of the dengue virus through virtual screening and evaluate its in vitro antiviral effect on DENV-2. Molecular docking was performed on NS5 using AutoDock Vina software, and compounds with physicochemical and pharmacological properties of interest were selected. The preliminary antivira
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17

Agis-Juárez, Raúl Azael, Iván Galván, Fernando Medina, et al. "Polypyrimidine tract-binding protein is relocated to the cytoplasm and is required during dengue virus infection in Vero cells." Journal of General Virology 90, no. 12 (2009): 2893–901. http://dx.doi.org/10.1099/vir.0.013433-0.

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The 3′ untranslated region (3′UTR) of the dengue virus (DENV) genome contain several sequences required for translation, replication and cyclization processes. This region also binds cellular proteins such as La, polypyrimidine tract-binding protein (PTB), Y box-binding protein 1, poly(A)-binding protein and the translation initiation factor eEF-1α. PTB is a cellular protein that interacts with the regulatory sequences of positive-strand RNA viruses such as several picornaviruses and hepatitis C virus. In the present report, it was demonstrated that PTB translocates from the nucleus to the cyt
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18

Friebe, Peter, and Eva Harris. "Interplay of RNA Elements in the Dengue Virus 5′ and 3′ Ends Required for Viral RNA Replication." Journal of Virology 84, no. 12 (2010): 6103–18. http://dx.doi.org/10.1128/jvi.02042-09.

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ABSTRACT Dengue virus (DENV) is a member of the Flavivirus genus of positive-sense RNA viruses. DENV RNA replication requires cyclization of the viral genome mediated by two pairs of complementary sequences in the 5′ and 3′ ends, designated 5′ and 3′ cyclization sequences (5′-3′ CS) and the 5′ and 3′ upstream of AUG region (5′-3′ UAR). Here, we demonstrate that another stretch of six nucleotides in the 5′ end is involved in DENV replication and possibly genome cyclization. This new sequence is located downstream of the AUG, designated the 5′ downstream AUG region (5′ DAR); the motif predicted
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19

Li, Qingxin, and Congbao Kang. "Structures and Dynamics of Dengue Virus Nonstructural Membrane Proteins." Membranes 12, no. 2 (2022): 231. http://dx.doi.org/10.3390/membranes12020231.

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Dengue virus is an important human pathogen threating people, especially in tropical and sub-tropical regions. The viral genome has one open reading frame and encodes one polyprotein which can be processed into structural and nonstructural (NS) proteins. Four of the seven nonstructural proteins, NS2A, NS2B, NS4A and NS4B, are membrane proteins. Unlike NS3 or NS5, these proteins do not harbor any enzymatic activities, but they play important roles in viral replication through interactions with viral or host proteins to regulate important pathways and enzymatic activities. The location of these
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Chatel-Chaix, Laurent, Wolfgang Fischl, Pietro Scaturro, et al. "A Combined Genetic-Proteomic Approach Identifies Residues within Dengue Virus NS4B Critical for Interaction with NS3 and Viral Replication." Journal of Virology 89, no. 14 (2015): 7170–86. http://dx.doi.org/10.1128/jvi.00867-15.

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ABSTRACTDengue virus (DENV) infection causes the most prevalent arthropod-borne viral disease worldwide. Approved vaccines are not available, and targets suitable for the development of antiviral drugs are lacking. One possible drug target is nonstructural protein 4B (NS4B), because it is absolutely required for virus replication; however, its exact role in the DENV replication cycle is largely unknown. With the aim of mapping NS4B determinants critical for DENV replication, we performed a reverse genetic screening of 33 NS4B mutants in the context of an infectious DENV genome. While the major
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Yu, Li, and Lewis Markoff. "The Topology of Bulges in the Long Stem of the Flavivirus 3′ Stem-Loop Is a Major Determinant of RNA Replication Competence." Journal of Virology 79, no. 4 (2005): 2309–24. http://dx.doi.org/10.1128/jvi.79.4.2309-2324.2005.

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ABSTRACT All flavivirus genomes contain a 3′terminal stem-loop secondary structure (3′SL) formed by the most downstream ∼100 nucleotides (nt) of the viral RNA. The 3′SL is required for virus replication and has been shown to bind both virus-coded and cellular proteins. Results of the present study using an infectious DNA for WN virus strain 956 initially demonstrated that the dengue virus serotype 2 (DEN2) 3′SL nucleotide sequence could not substitute for that of the WN 3′SL to support WN genome replication. To determine what WN virus-specific 3′SL nucleotide sequences were required for WN vir
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Huang, Claire Y. H., Siritorn Butrapet, Dennis J. Pierro, et al. "Chimeric Dengue Type 2 (Vaccine Strain PDK-53)/Dengue Type 1 Virus as a Potential Candidate Dengue Type 1 Virus Vaccine." Journal of Virology 74, no. 7 (2000): 3020–28. http://dx.doi.org/10.1128/jvi.74.7.3020-3028.2000.

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ABSTRACT We constructed chimeric dengue type 2/type 1 (DEN-2/DEN-1) viruses containing the nonstructural genes of DEN-2 16681 virus or its vaccine derivative, strain PDK-53, and the structural genes (encoding capsid protein, premembrane protein, and envelope glycoprotein) of DEN-1 16007 virus or its vaccine derivative, strain PDK-13. We previously reported that attenuation markers of DEN-2 PDK-53 virus were encoded by genetic loci located outside the structural gene region of the PDK-53 virus genome. Chimeric viruses containing the nonstructural genes of DEN-2 PDK-53 virus and the structural g
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van den Elsen, Kaïn, Jun Ping Quek, and Dahai Luo. "Molecular Insights into the Flavivirus Replication Complex." Viruses 13, no. 6 (2021): 956. http://dx.doi.org/10.3390/v13060956.

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Flaviviruses are vector-borne RNA viruses, many of which are clinically relevant human viral pathogens, such as dengue, Zika, Japanese encephalitis, West Nile and yellow fever viruses. Millions of people are infected with these viruses around the world each year. Vaccines are only available for some members of this large virus family, and there are no effective antiviral drugs to treat flavivirus infections. The unmet need for vaccines and therapies against these flaviviral infections drives research towards a better understanding of the epidemiology, biology and immunology of flaviviruses. In
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Faheem, Muhammad, Jônatas Cunha Barbosa Lima, Syed Babar Jamal, Paula Andreia Silva, and João Alexandre Ribeiro Gonçalves Barbosa. "An insight into dengue virus proteins as potential drug/vaccine targets." Future Virology 14, no. 10 (2019): 671–91. http://dx.doi.org/10.2217/fvl-2019-0107.

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Dengue virus (DENV) is an arbovirus that belongs to family flaviviridae. Its genome is composed of a single stranded RNA molecule that encodes a single polyprotein. The polyprotein is processed by viral and cellular proteases to generate ten viral proteins. There are four antigenically distinct serotypes of DENV (DENV1, DENV2, DENV3 and DENV4), which are genetically related. Although protein variability is a major problem in dengue treatment, the functional and structural studies of individual proteins are equally important in treatment development. The data accumulated on dengue proteins are
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VADDADI, K., C. GANDIKOTA, and M. VENKATARAMANA. "Complete genome characterization and evolutionary analysis of serotype-4 associated with severe dengue." Epidemiology and Infection 145, no. 7 (2017): 1443–50. http://dx.doi.org/10.1017/s0950268817000243.

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SUMMARYDengue virus circulates as four independent serotypes posing a major public health threat around the globe. In the recent years, frequent dengue outbreaks are being reported in many parts of the world including India. Among four serotypes, Den-4 is the least sampled and studied serotype until recent times, but the reported cases with Den-4 infections were mostly known to associate with severe dengue. In the past three decades, only one complete genome sequence of Den-4 has been published from India. Hence there is a deficit in information with reference to this serotype which would be r
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SANTOS, JEFFERSON J. S., MARLI T. CORDEIRO, GIOVANI R. BERTANI, ERNESTO T. A. MARQUES, and LAURA H. V. G. GIL. "A two-plasmid strategy for engineering a dengue virus type 3 infectious clone from primary Brazilian isolate." Anais da Academia Brasileira de Ciências 86, no. 4 (2014): 1749–59. http://dx.doi.org/10.1590/0001-3765201420130332.

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Dengue infections represent one of the most prevalent arthropod-borne diseases worldwide, causing a wide spectrum of clinical outcomes. Engineered infectious clone is an important tool to study Dengue virus (DENV) biology. Functional full-length cDNA clones have been constructed for many positive-strand RNA viruses and have provided valuable tools for studying the molecular mechanisms involved in viral genome replication, virion assembly, virus pathogenesis and vaccine development. We report herein the successful development of an infectious clone from a primary Brazilian isolate of dengue vir
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Huang, Claire Y. H., Siritorn Butrapet, Kiyotaka R. Tsuchiya, Natth Bhamarapravati, Duane J. Gubler, and Richard M. Kinney. "Dengue 2 PDK-53 Virus as a Chimeric Carrier for Tetravalent Dengue Vaccine Development." Journal of Virology 77, no. 21 (2003): 11436–47. http://dx.doi.org/10.1128/jvi.77.21.11436-11447.2003.

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ABSTRACT Attenuation markers of the candidate dengue 2 (D2) PDK-53 vaccine virus are encoded by mutations that reside outside of the structural gene region of the genome. We engineered nine dengue virus chimeras containing the premembrane (prM) and envelope (E) genes of wild-type D1 16007, D3 16562, or D4 1036 virus within the genetic backgrounds of wild-type D2 16681 virus and the two genetic variants (PDK53-E and PDK53-V) of the D2 PDK-53 vaccine virus. Expression of the heterologous prM-E genes in the genetic backgrounds of the two D2 PDK-53 variants, but not that of wild-type D2 16681 viru
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Yap, Thai Leong, Ting Xu, Yen-Liang Chen, et al. "Crystal Structure of the Dengue Virus RNA-Dependent RNA Polymerase Catalytic Domain at 1.85-Angstrom Resolution." Journal of Virology 81, no. 9 (2007): 4753–65. http://dx.doi.org/10.1128/jvi.02283-06.

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ABSTRACT Dengue fever, a neglected emerging disease for which no vaccine or antiviral agents exist at present, is caused by dengue virus, a member of the Flavivirus genus, which includes several important human pathogens, such as yellow fever and West Nile viruses. The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue vi
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de Borba, Luana, Sergio M. Villordo, Nestor G. Iglesias, Claudia V. Filomatori, Leopoldo G. Gebhard, and Andrea V. Gamarnik. "Overlapping Local and Long-Range RNA-RNA Interactions Modulate Dengue Virus Genome Cyclization and Replication." Journal of Virology 89, no. 6 (2015): 3430–37. http://dx.doi.org/10.1128/jvi.02677-14.

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The dengue virus genome is a dynamic molecule that adopts different conformations in the infected cell. Here, using RNA folding predictions, chemical probing analysis, RNA binding assays, and functional studies, we identified newcis-acting elements present in the capsid coding sequence that facilitate cyclization of the viral RNA by hybridization with a sequence involved in a local dumbbell structure at the viral 3′ untranslated region (UTR). The identified interaction differentially enhances viral replication in mosquito and mammalian cells.
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Hodge, Kenneth, Chairat Tunghirun, Maliwan Kamkaew, Thawornchai Limjindaporn, Pa-thai Yenchitsomanus, and Sarin Chimnaronk. "Identification of a Conserved RNA-dependent RNA Polymerase (RdRp)-RNA Interface Required for Flaviviral Replication." Journal of Biological Chemistry 291, no. 33 (2016): 17437–49. http://dx.doi.org/10.1074/jbc.m116.724013.

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Dengue virus, an ∼10.7-kb positive-sense RNA virus, is the most common arthropod-communicated pathogen in the world. Despite dengue's clear epidemiological importance, mechanisms for its replication remain elusive. Here, we probed the entire dengue genome for interactions with viral RNA-dependent RNA polymerase (RdRp), and we identified the dominant interaction as a loop-forming ACAG motif in the 3′ positive-stranded terminus, complicating the prevailing model of replication. A subset of interactions coincides with known flaviviral recombination sites inside the viral protein-coding region. Sp
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Vial, Thomas, Wei-Lian Tan, Eric Deharo, Dorothée Missé, Guillaume Marti, and Julien Pompon. "Mosquito metabolomics reveal that dengue virus replication requires phospholipid reconfiguration via the remodeling cycle." Proceedings of the National Academy of Sciences 117, no. 44 (2020): 27627–36. http://dx.doi.org/10.1073/pnas.2015095117.

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Dengue virus (DENV) subdues cell membranes for its cellular cycle by reconfiguring phospholipids in humans and mosquitoes. Here, we determined how and why DENV reconfigures phospholipids in the mosquito vector. By inhibiting and activating the de novo phospholipid biosynthesis, we demonstrated the antiviral impact of de novo–produced phospholipids. In line with the virus hijacking lipids for its benefit, metabolomics analyses indicated that DENV actively inhibited the de novo phospholipid pathway and instead triggered phospholipid remodeling. We demonstrated the early induction of remodeling d
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Kinney, Richard M., Claire Y. H. Huang, Becky C. Rose, et al. "Inhibition of Dengue Virus Serotypes 1 to 4 in Vero Cell Cultures with Morpholino Oligomers." Journal of Virology 79, no. 8 (2005): 5116–28. http://dx.doi.org/10.1128/jvi.79.8.5116-5128.2005.

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ABSTRACT Five dengue (DEN) virus-specific R5F2R4 peptide-conjugated phosphorodiamidate morpholino oligomers (P4-PMOs) were evaluated for their ability to inhibit replication of DEN virus serotype 2 (DEN-2 virus) in mammalian cell culture. Initial growth curves of DEN-2 virus 16681 were obtained in Vero cells incubated with 20 μM P4-PMO compounds. At 6 days after infection, a P4-PMO targeting the 3′-terminal nucleotides of the DEN-2 virus genome and a random-sequence P4-PMO showed relatively little suppression of DEN-2 virus titer (0.1 and 0.9 log10, respectively). P4-PMOs targeting the AUG tra
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Cologna, Raymond, and Rebeca Rico-Hesse. "American Genotype Structures Decrease Dengue Virus Output from Human Monocytes and Dendritic Cells." Journal of Virology 77, no. 7 (2003): 3929–38. http://dx.doi.org/10.1128/jvi.77.7.3929-3938.2003.

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ABSTRACT The dengue virus type 2 structures probably involved in human virulence were previously defined by sequencing the complete genome of both American and Southeast (SE) Asian genotype templates in patient serum (K. C. Leitmeyer et al., J. Virol. 73:4738-4747, 1999). We have now evaluated the effects of introducing a mutation in the envelope glycoprotein (E) gene and/or replacement of 5′- and 3′-nontranslated regions on dengue virus replication in human primary cell cultures. A series of chimeric infectious clones were generated containing different combinations of American and SE Asian g
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Cerikan, Berati, Sarah Goellner, Christopher John Neufeldt, et al. "A Non-Replicative Role of the 3′ Terminal Sequence of the Dengue Virus Genome in Membranous Replication Organelle Formation." Cell Reports 32, no. 1 (2020): 107859. http://dx.doi.org/10.1016/j.celrep.2020.107859.

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Hosseini, Samira, Rodrigo B. Muñoz-Soto, Jacqueline Oliva-Ramírez, et al. "Latest Updates in Dengue Fever Therapeutics: Natural, Marine and Synthetic Drugs." Current Medicinal Chemistry 27, no. 5 (2020): 719–44. http://dx.doi.org/10.2174/0929867325666180629124709.

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In this paper, we review the history of Dengue, the mechanism of infection, the molecular characteristics and components of Dengue, the mechanism of entry to the target cells, cyclization of the genome and replication process, as well as translation of the proteins for virus assembly. The major emphasis of this work is on natural products and plant extracts, which were used for as palliative or adjuvant treatment of Dengue. This review article also summarizes the latest findings in regards to the marine products as effective drugs to target different symptoms of Dengue. Furthermore, an update
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Naik, Nenavath Gopal, and Huey-Nan Wu. "Mutation of Putative N-Glycosylation Sites on Dengue Virus NS4B Decreases RNA Replication." Journal of Virology 89, no. 13 (2015): 6746–60. http://dx.doi.org/10.1128/jvi.00423-15.

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ABSTRACTDengue virus (DENV) nonstructural protein 4B (NS4B) is an endoplasmic reticulum (ER) membrane-associated protein, and mutagenesis studies have revealed its significance in viral genome replication. In this work, we demonstrated that NS4B is an N-glycosylated protein in virus-infected cells as well as in recombinant protein expression. NS4B is N glycosylated at residues 58 and 62 and exists in two forms, glycosylated and unglycosylated. We manipulated full-length infectious RNA clones and subgenomic replicons to generate N58Q, N62Q, and N58QN62Q mutants. Each of the single mutants had d
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Bagchi, Parikshit, Kaitlyn Speckhart, Andrew Kennedy, Andrew W. Tai, and Billy Tsai. "A specific EMC subunit supports Dengue virus infection by promoting virus membrane fusion essential for cytosolic genome delivery." PLOS Pathogens 18, no. 7 (2022): e1010717. http://dx.doi.org/10.1371/journal.ppat.1010717.

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Dengue virus (DENV) represents the most common human arboviral infection, yet its cellular entry mechanism remains unclear. The multi-subunit endoplasmic reticulum membrane complex (EMC) supports DENV infection, in part, by assisting the biosynthesis of viral proteins critical for downstream replication steps. Intriguingly, the EMC has also been shown to act at an earlier step prior to viral protein biogenesis, although this event is not well-defined. Here we demonstrate that the EMC subunit EMC4 promotes fusion of the DENV and endosomal membranes during entry, enabling delivery of the viral g
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Zeng, Lingling, Barry Falgout, and Lewis Markoff. "Identification of Specific Nucleotide Sequences within the Conserved 3′-SL in the Dengue Type 2 Virus Genome Required for Replication." Journal of Virology 72, no. 9 (1998): 7510–22. http://dx.doi.org/10.1128/jvi.72.9.7510-7522.1998.

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ABSTRACT The flavivirus genome is a positive-stranded ∼11-kb RNA including 5′ and 3′ noncoding regions (NCR) of approximately 100 and 400 to 600 nucleotides (nt), respectively. The 3′ NCR contains adjacent, thermodynamically stable, conserved short and long stem-and-loop structures (the 3′-SL), formed by the 3′-terminal ∼100 nt. The nucleotide sequences within the 3′-SL are not well conserved among species. We examined the requirement for the 3′-SL in the context of dengue virus type 2 (DEN2) replication by mutagenesis of an infectious cDNA copy of a DEN2 genome. Genomic full-length RNA was tr
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Tilston-Lunel, Natasha L., Gustavo Olszanski Acrani, Richard E. Randall, and Richard M. Elliott. "Generation of Recombinant Oropouche Viruses Lacking the Nonstructural Protein NSm or NSs." Journal of Virology 90, no. 5 (2015): 2616–27. http://dx.doi.org/10.1128/jvi.02849-15.

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ABSTRACTOropouche virus (OROV) is a midge-borne human pathogen with a geographic distribution in South America. OROV was first isolated in 1955, and since then, it has been known to cause recurring outbreaks of a dengue-like illness in the Amazonian regions of Brazil. OROV, however, remains one of the most poorly understood emerging viral zoonoses. Here we describe the successful recovery of infectious OROV entirely from cDNA copies of its genome and generation of OROV mutant viruses lacking either the NSm or the NSs coding region. Characterization of the recombinant viruses carried outin vitr
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St Clair, Laura A., Stephanie A. Mills, Elena Lian, et al. "Acyl-Coa Thioesterases: A Rheostat That Controls Activated Fatty Acids Modulates Dengue Virus Serotype 2 Replication." Viruses 14, no. 2 (2022): 240. http://dx.doi.org/10.3390/v14020240.

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During infection with dengue viruses (DENVs), the lipid landscape within host cells is significantly altered to assemble membrane platforms that support viral replication and particle assembly. Fatty acyl-CoAs are key intermediates in the biosynthesis of complex lipids that form these membranes. They also function as key signaling lipids in the cell. Here, we carried out loss of function studies on acyl-CoA thioesterases (ACOTs), a family of enzymes that hydrolyze fatty acyl-CoAs to free fatty acids and coenzyme A, to understand their influence on the lifecycle of DENVs. The loss of function o
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Wang, Sai, Kitti W. K. Chan, Kishore B. Naripogu, Crystall M. D. Swarbrick, John Aaskov, and Subhash G. Vasudevan. "Subgenomic RNA from Dengue Virus Type 2 Suppresses Replication of Dengue Virus Genomes and Interacts with Virus-Encoded NS3 and NS5 Proteins." ACS Infectious Diseases 6, no. 3 (2020): 436–46. http://dx.doi.org/10.1021/acsinfecdis.9b00384.

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Blair, Carol D., Zachary N. Adelman, and Ken E. Olson. "Molecular Strategies for Interrupting Arthropod-Borne Virus Transmission by Mosquitoes." Clinical Microbiology Reviews 13, no. 4 (2000): 651–61. http://dx.doi.org/10.1128/cmr.13.4.651.

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SUMMARY Arthropod-borne virus (arbovirus) infections cause a number of emerging and resurgent human and veterinary infectious diseases. Traditional means of controlling arbovirus diseases include vaccination of susceptible vertebrates and mosquito control, but in many cases these have been unavailable or ineffective, and so novel strategies for disease control are needed. One possibility is genetic manipulation of mosquito vectors to render them unable to transmit arboviruses. This review describes recent work to test the concept of pathogen-derived resistance in arthropods by expression of vi
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Lindenbach, Brett D., and Charles M. Rice. "Genetic Interaction of Flavivirus Nonstructural Proteins NS1 and NS4A as a Determinant of Replicase Function." Journal of Virology 73, no. 6 (1999): 4611–21. http://dx.doi.org/10.1128/jvi.73.6.4611-4621.1999.

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ABSTRACT Nonstructural protein 1 (NS1) of yellow fever virus (YF) is a glycoprotein localized to extracytoplasmic compartments within infected cells. We have previously shown that NS1 can be supplied intrans and is required for viral RNA replication, a process thought to occur in membrane-bound cytoplasmic complexes. Here we report that the NS1 gene from a related virus, dengue virus (DEN), is unable to function in the process of YF RNA replication. This virus-specific incompatibility leads to a lack of initial minus-strand accumulation, suggesting that DEN NS1 is unable to productively intera
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Edgil, Dianna, Charlotta Polacek, and Eva Harris. "Dengue Virus Utilizes a Novel Strategy for Translation Initiation When Cap-Dependent Translation Is Inhibited." Journal of Virology 80, no. 6 (2006): 2976–86. http://dx.doi.org/10.1128/jvi.80.6.2976-2986.2006.

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ABSTRACT Viruses have developed numerous mechanisms to usurp the host cell translation apparatus. Dengue virus (DEN) and other flaviviruses, such as West Nile and yellow fever viruses, contain a 5′ m7GpppN-capped positive-sense RNA genome with a nonpolyadenylated 3′ untranslated region (UTR) that has been presumed to undergo translation in a cap-dependent manner. However, the means by which the DEN genome is translated effectively in the presence of capped, polyadenylated cellular mRNAs is unknown. This report demonstrates that DEN replication and translation are not affected under conditions
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Helt, Anna-Marija, and Eva Harris. "S-Phase-Dependent Enhancement of Dengue Virus 2 Replication in Mosquito Cells, but Not in Human Cells." Journal of Virology 79, no. 21 (2005): 13218–30. http://dx.doi.org/10.1128/jvi.79.21.13218-13230.2005.

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ABSTRACT Dengue virus (DEN) is the most prevalent cause of arthropod-borne viral illness in humans. We determined the influence of cellular growth state on DEN type 2 (DEN2) replication in mosquito and human cells, based on the hypothesis that manipulation of cellular growth state will facilitate identification of viral and cellular determinants of productive infection. Comparison of density-arrested and cycling C6/36 Aedes albopictus cells infected with a low-passage DEN2 isolate revealed that cycling cells generated higher virus titers per cell. When C6/36 cells were stalled in S-phase via a
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Villordo, S. M., D. E. Alvarez, and A. V. Gamarnik. "A balance between circular and linear forms of the dengue virus genome is crucial for viral replication." RNA 16, no. 12 (2010): 2325–35. http://dx.doi.org/10.1261/rna.2120410.

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47

Syenina, Ayesa, Dhanasekaran Vijaykrishna, Esther Shuyi Gan, et al. "Positive epistasis between viral polymerase and the 3′ untranslated region of its genome reveals the epidemiologic fitness of dengue virus." Proceedings of the National Academy of Sciences 117, no. 20 (2020): 11038–47. http://dx.doi.org/10.1073/pnas.1919287117.

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Dengue virus (DENV) is a global health threat, causing repeated epidemics throughout the tropical world. While low herd immunity levels to any one of the four antigenic types of DENV predispose populations to outbreaks, viral genetic determinants that confer greater fitness for epidemic spread is an important but poorly understood contributor of dengue outbreaks. Here we report that positive epistasis between the coding and noncoding regions of the viral genome combined to elicit an epidemiologic fitness phenotype associated with the 1994 DENV2 outbreak in Puerto Rico. We found that five amino
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Dungdung, Ranjeet, Manikanta Bayal, Lathika Valliyott, Unnikrishnan Unniyampurath, Swapna S. Nair, and Rajendra Pilankatta. "A slow, efficient and safe nanoplatform of tailored ZnS QD-mycophenolic acid conjugates for in vitro drug delivery against dengue virus 2 genome replication." Nanoscale Advances 2, no. 12 (2020): 5777–89. http://dx.doi.org/10.1039/d0na00725k.

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The graphical abstract represents the synthesis of size engineered ZnS QDs for conjugating anti-viral drug (MPA) and its safe and effective delivery against cytoplasmically replicating dengue virus 2.
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Green, Timothy J., Peter Speck, Lu Geng, David Raftos, Michael R. Beard, and Karla J. Helbig. "Oyster viperin retains direct antiviral activity and its transcription occurs via a signalling pathway involving a heat-stable haemolymph protein." Journal of General Virology 96, no. 12 (2015): 3587–97. http://dx.doi.org/10.1099/jgv.0.000300.

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Little is known about the response of non-model invertebrates, such as oysters, to virus infection. The vertebrate innate immune system detects virus-derived nucleic acids to trigger the type I IFN pathway, leading to the transcription of hundreds of IFN-stimulated genes (ISGs) that exert antiviral functions. Invertebrates were thought to lack the IFN pathway based on the absence of IFN or ISGs encoded in model invertebrate genomes. However, the oyster genome encodes many ISGs, including the well-described antiviral protein viperin. In this study, we characterized oyster viperin and showed tha
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Wahongan, Irma F., Elly J. Suoth, Fatimawali, et al. "Designing an Epitope-Based Peptide Vaccine Derived from RNA-Dependent RNA Polymerase (RdRp) against Dengue Virus Serotype 2." Vaccines 10, no. 10 (2022): 1734. http://dx.doi.org/10.3390/vaccines10101734.

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Dengue fever (DF) continues to be one of the tropical and subtropical health concerns. Its prevalence tends to increase in some places in these regions. This disease is caused by the dengue virus (DENV), which is transmitted through the mosquitoes Aedes aegypti and A. albopictus. The treatment of DF to date is only supportive and there is no definitive vaccine to prevent this disease. The non-structural DENV protein, RNA-dependent RNA Polymerase (RdRp), is involved in viral replication. The RdRp-derived peptides can be used in the construction of a universal dengue vaccine. These peptides can
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