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https://www.readbyqxmd.com/read/27746901/illustrating-and-homology-modeling-the-proteins-of-the-zika-virus
#1
Sean Ekins, John Liebler, Bruno J Neves, Warren G Lewis, Megan Coffee, Rachelle Bienstock, Christopher Southan, Carolina H Andrade
The Zika virus (ZIKV) is a flavivirus of the family Flaviviridae, which is similar to dengue virus, yellow fever and West Nile virus. Recent outbreaks in South America, Latin America, the Caribbean and in particular Brazil have led to concern for the spread of the disease and potential to cause Guillain-Barré syndrome and microcephaly. Although ZIKV has been known of for over 60 years there is very little in the way of knowledge of the virus with few publications and no crystal structures. No antivirals have been tested against it either in vitro or in vivo...
2016: F1000Research
https://www.readbyqxmd.com/read/27443615/hla-drb1-alleles-are-associated-with-different-magnitudes-of-dengue-virus-specific-cd4-t-cell-responses
#2
Daniela Weiskopf, Michael A Angelo, Alba Grifoni, Patrick H O'Rourke, John Sidney, Sinu Paul, Aruna D De Silva, Elizabeth Phillips, Simon Mallal, Sunil Premawansa, Gayani Premawansa, Ananda Wijewickrama, Bjoern Peters, Alessandro Sette
BACKGROUND: Each year dengue virus (DENV) infects 400 million human but causes symptomatic disease in only a subset of patients, suggesting that host genetic factors may play a role. HLA molecules that restrict T-cell responses are one of the most polymorphic host factors in humans. METHODS: Here we map HLA DRB1-restricted DENV-specific epitopes in individuals previously exposed to DENV, to identify the breadth and specificity of CD4(+) T-cell responses. To investigate whether HLA-specific variations in the magnitude of response might predict associations between dengue outcomes and HLA-DRB1 alleles, we assembled samples from hospitalized patients with known severity of disease...
October 1, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27296393/predicting-zika-virus-structural-biology-challenges-and-opportunities-for-intervention
#3
Bryan D Cox, Richard A Stanton, Raymond F Schinazi
BACKGROUND: Zika virus is an emerging crisis as infection is implicated in severe neurological disorders-Guillain-Barré syndrome and fetal microcephaly. There are currently no treatment options available for Zika virus infection. This virus is part of the flavivirus genus and closely related to Dengue Fever Virus, West Nile Virus, and Japanese Encephalitis Virus. Like other flaviviruses, the Zika virus genome encodes three structural proteins (capsid, precursor membrane, and envelope) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5)...
August 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/27169727/population-genomics-of-dengue-virus-serotype-4-insights-into-genetic-structure-and-evolution
#4
Vaishali P Waman, Sunitha Manjari Kasibhatla, Mohan M Kale, Urmila Kulkarni-Kale
The spread of dengue disease has become a global public health concern. Dengue is caused by dengue virus, which is a mosquito-borne arbovirus of the genus Flavivirus, family Flaviviridae. There are four dengue virus serotypes (1-4), each of which is known to trigger mild to severe disease. Dengue virus serotype 4 (DENV-4) has four genotypes and is increasingly being reported to be re-emerging in various parts of the world. Therefore, the population structure and factors shaping the evolution of DENV-4 strains across the world were studied using genome-based population genetic, phylogenetic and selection pressure analysis methods...
August 2016: Archives of Virology
https://www.readbyqxmd.com/read/26377679/proteolytic-cleavage-analysis-at-the-murray-valley-encephalitis-virus-ns1-2a-junction
#5
COMPARATIVE STUDY
Siti Nor Khadijah Addis, Eva Lee, Jayaram Bettadapura, Mario Lobigs
BACKGROUND: Our understanding of the proteolytic processing events at the NS1-2A junction in the flavivirus polyprotein has not markedly progressed since the early work conducted on dengue virus (DENV). This work identified an octapeptide sequence located immediately upstream of the cleavage site thought to be important in substrate recognition by an as yet unknown, endoplasmic reticulum-resident host protease. Of the eight amino acid recognition sequence, the highly conserved residues at positions P1, P3, P5, P7 and P8 (with respect to N-terminus of NS2A) are particularly sensitive to amino acid substitutions in terms of DENV NS1-NS2A cleavage efficiency; however, the role of the octapeptide in efficient NS1 and NS2A production of other flaviviruses has not been experimentally addressed...
2015: Virology Journal
https://www.readbyqxmd.com/read/25968648/dengue-virus-ns-proteins-inhibit-rig-i-mavs-signaling-by-blocking-tbk1-irf3-phosphorylation-dengue-virus-serotype-1-ns4a-is-a-unique-interferon-regulating-virulence-determinant
#6
Nadine A Dalrymple, Velasco Cimica, Erich R Mackow
UNLABELLED: Dengue virus (DENV) replication is inhibited by the prior addition of type I interferon or by RIG-I agonists that elicit RIG-I/MAVS/TBK1/IRF3-dependent protective responses. DENV infection of primary human endothelial cells (ECs) results in a rapid increase in viral titer, which suggests that DENV inhibits replication-restrictive RIG-I/interferon beta (IFN-β) induction pathways within ECs. Our findings demonstrate that DENV serotype 4 (DENV4) nonstructural (NS) proteins NS2A and NS4B inhibited RIG-I-, MDA5-, MAVS-, and TBK1/IKKε-directed IFN-β transcription (>80%) but failed to inhibit IFN-β induction directed by STING or constitutively active IRF3-5D...
May 12, 2015: MBio
https://www.readbyqxmd.com/read/25915765/profiling-of-viral-proteins-expressed-from-the-genomic-rna-of-japanese-encephalitis-virus-using-a-panel-of-15-region-specific-polyclonal-rabbit-antisera-implications-for-viral-gene-expression
#7
Jin-Kyoung Kim, Jeong-Min Kim, Byung-Hak Song, Sang-Im Yun, Gil-Nam Yun, Sung-June Byun, Young-Min Lee
Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is closely related to West Nile (WN), yellow fever (YF), and dengue (DEN) viruses. Its plus-strand genomic RNA carries a single open reading frame encoding a polyprotein that is cleaved into three structural (C, prM/M, and E) and at least seven nonstructural (NS1/NS1', NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins, based on previous work with WNV, YFV, and DENV. Here, we aimed to profile experimentally all the viral proteins found in JEV-infected cells...
2015: PloS One
https://www.readbyqxmd.com/read/25811657/clinical-outcome-and-genetic-differences-within-a-monophyletic-dengue-virus-type-2-population
#8
Hapuarachchige Chanditha Hapuarachchi, Rachel Choon Rong Chua, Yuan Shi, Tun Lin Thein, Linda Kay Lee, Kim Sung Lee, David Chien Lye, Lee Ching Ng, Yee Sin Leo
The exact mechanisms of interplay between host and viral factors leading to severe dengue are yet to be fully understood. Even though previous studies have implicated specific genetic differences of Dengue virus (DENV) in clinical severity and virus attenuation, similar studies with large-scale, whole genome screening of monophyletic virus populations are limited. Therefore, in the present study, we compared 89 whole genomes of DENV-2 cosmopolitan clade III isolates obtained from patients diagnosed with dengue fever (DF, n = 58), dengue hemorrhagic fever (DHF, n = 30) and dengue shock syndrome (DSS, n = 1) in Singapore between July 2010 and January 2013, in order to determine the correlation of observed viral genetic differences with clinical outcomes...
2015: PloS One
https://www.readbyqxmd.com/read/25653435/scanning-mutagenesis-studies-reveal-a-potential-intramolecular-interaction-within-the-c-terminal-half-of-dengue-virus-ns2a-involved-in-viral-rna-replication-and-virus-assembly-and-secretion
#9
Ren-Huang Wu, Ming-Han Tsai, Day-Yu Chao, Andrew Yueh
UNLABELLED: The NS2A protein of dengue virus (DENV) has eight predicted transmembrane segments (pTMSs; pTMS1 to pTMS8). NS2A has been shown to participate in RNA replication, virion assembly, and the host antiviral response. However, the role of the amino acid residues within the pTMS regions of NS2A during the virus life cycle is poorly understood. In the study described here, we explored the function of DENV NS2A by introducing a series of double or triple alanine substitutions into the C-terminal half (pTMS4 to pTMS8) of NS2A in the context of a DENV infectious clone or subgenomic replicon...
April 2015: Journal of Virology
https://www.readbyqxmd.com/read/25629430/dengue-virus-control-of-type-i-ifn-responses-a-history-of-manipulation-and-control
#10
REVIEW
Jorge Andrés Castillo Ramirez, Silvio Urcuqui-Inchima
The arthropod-borne diseases caused by dengue virus (DENV) are a major and emerging problem of public health worldwide. Infection with DENV causes a series of clinical manifestations ranging from mild flu syndrome to severe diseases that include hemorrhage and shock. It has been demonstrated that the innate immune response plays a key role in DENV pathogenesis. However, in recent years, it was shown that DENV evades the innate immune response by blocking type I interferon (IFN-I). It has been demonstrated that DENV can inhibit both the production and the signaling of IFN-I...
June 2015: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/25568208/characterization-of-dengue-virus-ns4a-and-ns4b-protein-interaction
#11
Jing Zou, Xuping Xie, Qing-Yin Wang, Hongping Dong, Michelle Yueqi Lee, Congbao Kang, Zhiming Yuan, Pei-Yong Shi
UNLABELLED: Flavivirus replication is mediated by a membrane-associated replication complex where viral membrane proteins NS2A, NS2B, NS4A, and NS4B serve as the scaffold for the replication complex formation. Here, we used dengue virus serotype 2 (DENV-2) as a model to characterize viral NS4A-NS4B interaction. NS4A interacts with NS4B in virus-infected cells and in cells transiently expressing NS4A and NS4B in the absence of other viral proteins. Recombinant NS4A and NS4B proteins directly bind to each other with an estimated Kd (dissociation constant) of 50 nM...
April 2015: Journal of Virology
https://www.readbyqxmd.com/read/25449574/identification-of-conserved-and-hla-a-2402-restricted-epitopes-in-dengue-virus-serotype-2
#12
Zhi-Liang Duan, Hui-Fang Liu, Xi Huang, Si-Na Wang, Jin-Lin Yang, Xin-Yu Chen, De-Zhou Li, Xiao-Zhi Zhong, Bo-Kun Chen, Jin-Sheng Wen
In this study, we set out to identify dengue virus serotype 2 (DENV-2)-specific HLA-A*2402-restricted epitopes and determine the characteristics of T cells generated to these epitopes. We screened the full-length amino-acid sequence of DENV-2 to find potential epitopes using the SYFPEITHI algorithm. Twelve putative HLA-A*2402-binding peptides conserved in hundreds of DENV-2 strains were synthesized, and the HLA restriction of peptides was tested in HLA-A*2402 transgenic mice. Nine peptides (NS4b(228-237), NS2a(73-81), E(298-306), M(141-149), NS4a(96-105), NS4b(159-168), NS5(475-484), NS1(162-171), and NS5(611-620)) induced high levels of peptide-specific IFN-γ-secreting cells in HLA-A*2402 transgenic mice...
January 22, 2015: Virus Research
https://www.readbyqxmd.com/read/25392211/two-distinct-sets-of-ns2a-molecules-are-responsible-for-dengue-virus-rna-synthesis-and-virion-assembly
#13
Xuping Xie, Jing Zou, Chunya Puttikhunt, Zhiming Yuan, Pei-Yong Shi
UNLABELLED: Flavivirus nonstructural protein 2A (NS2A) plays important roles in both viral RNA synthesis and virion assembly. The molecular details of how the NS2A protein modulates the two distinct events have not been defined. To address this question, we have performed a systematic mutagenesis of NS2A using dengue virus (DENV) serotype 2 (DENV-2) as a model. We identified two sets of NS2A mutations with distinct defects during a viral infection cycle. One set of NS2A mutations (D125A and G200A) selectively abolished viral RNA synthesis...
January 15, 2015: Journal of Virology
https://www.readbyqxmd.com/read/25119664/membrane-interacting-regions-of-dengue-virus-ns2a-protein
#14
Henrique Nemésio, José Villalaín
The Dengue virus (DENV) NS2A protein, essential for viral replication, is a poorly characterized membrane protein. NS2A displays both protein/protein and membrane/protein interactions, yet neither its functions in the viral cycle nor its active regions are known with certainty. To highlight the different membrane-active regions of NS2A, we characterized the effects of peptides derived from a peptide library encompassing this protein's full length on different membranes by measuring their membrane leakage induction and modulation of lipid phase behavior...
August 28, 2014: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/24696348/construction-of-plasmid-bacterial-expression-purification-and-assay-of-dengue-virus-type-2-ns5-methyltransferase
#15
Siwaporn Boonyasuppayakorn, Radhakrishnan Padmanabhan
Dengue virus (DENV), a member of mosquito-borne flavivirus, causes self-limiting dengue fever as well as life-threatening dengue hemorrhagic fever and dengue shock syndrome. Its positive sense RNA genome has a cap at the 5'-end and no poly(A) tail at the 3'-end. The viral RNA encodes a single polyprotein, C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5. The polyprotein is processed into 3 structural proteins (C, prM, and E) and 7 nonstructural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5). NS3 and NS5 are multifunctional enzymes performing various tasks in viral life cycle...
2014: Methods in Molecular Biology
https://www.readbyqxmd.com/read/24696347/construction-of-dengue-virus-protease-expression-plasmid-and-in-vitro-protease-assay-for-screening-antiviral-inhibitors
#16
Huiguo Lai, Tadahisa Teramoto, Radhakrishnan Padmanabhan
Dengue virus serotypes 1-4 (DENV1-4) are mosquito-borne human pathogens of global significance causing ~390 million cases annually worldwide. The virus infections cause in general a self-limiting disease, known as dengue fever, but occasionally also more severe forms, especially during secondary infections, dengue hemorrhagic fever and dengue shock syndrome causing ~25,000 deaths annually. The DENV genome contains a single-strand positive sense RNA, approximately 11 kb in length. The 5'-end has a type I cap structure...
2014: Methods in Molecular Biology
https://www.readbyqxmd.com/read/24696335/construction-of-self-replicating-subgenomic-dengue-virus-4-denv4-replicon
#17
Sofia L Alcaraz-Estrada, Rosa Del Angel, Radhakrishnan Padmanabhan
Dengue virus serotypes 1-4 are members of mosquito-borne flavivirus genus of Flaviviridae family that encode one long open reading frame (ORF) that is translated to a polyprotein. Both host and virally encoded proteases function in the processing of the polyprotein by co-translational and posttranslational mechanisms to yield 10 mature proteins prior to viral RNA replication. To study cis- and trans-acting factors involved in viral RNA replication, many groups [1-8] have constructed cDNAs encoding West Nile virus (WNV), DENV, or yellow fever virus reporter replicon RNAs...
2014: Methods in Molecular Biology
https://www.readbyqxmd.com/read/24647042/clinical-and-immunological-markers-of-dengue-progression-in-a-study-cohort-from-a-hyperendemic-area-in-malaysia
#18
Anusyah Rathakrishnan, Benjamin Klekamp, Seok Mui Wang, Thamil Vaani Komarasamy, Santha Kumari Natkunam, Jameela Sathar, Azliyati Azizan, Aurora Sanchez-Anguiano, Rishya Manikam, Shamala Devi Sekaran
BACKGROUND: With its elusive pathogenesis, dengue imposes serious healthcare, economic and social burden on endemic countries. This study describes the clinical and immunological parameters of a dengue cohort in a Malaysian city, the first according to the WHO 2009 dengue classification. METHODOLOGY AND FINDINGS: This longitudinal descriptive study was conducted in two Malaysian hospitals where patients aged 14 and above with clinical symptoms suggestive of dengue were recruited with informed consent...
2014: PloS One
https://www.readbyqxmd.com/read/24316047/innate-immunity-to-dengue-virus-infection-and-subversion-of-antiviral-responses
#19
REVIEW
Angela M Green, P Robert Beatty, Alexandros Hadjilaou, Eva Harris
Dengue is a major public health issue in tropical and subtropical regions worldwide. The four serotypes of dengue virus (DENV1-DENV4) are spread primarily by Aedes aegypti and Aedes albopictus mosquitoes, whose geographic range continues to expand. Humans are the only host for epidemic strains of DENV, and the virus has developed sophisticated mechanisms to evade human innate immune responses. The host cell's first line of defense begins with an intracellular signaling cascade resulting in production of interferon α/β (IFN-α/β), which promotes intracellular antiviral responses and helps initiates the adaptive response during the course of DENV infection...
March 20, 2014: Journal of Molecular Biology
https://www.readbyqxmd.com/read/24007412/evolution-and-heterogeneity-of-multiple-serotypes-of-dengue-virus-in-pakistan-2006-2011
#20
Carmen Koo, Amna Nasir, Hapuarachchige Chanditha Hapuarachchi, Kim-Sung Lee, Zahra Hasan, Lee-Ching Ng, Erum Khan
BACKGROUND: Even though dengue has been recognized as one of the major public health threats in Pakistan, the understanding of its molecular epidemiology is still limited. The genotypic diversity of Dengue virus (DENV) serotypes involved in dengue outbreaks since 2005 in Pakistan is not well studied. Here, we investigated the origin, diversity, genetic relationships and geographic distribution of DENV to understand virus evolution during the recent expansion of dengue in Pakistan. METHODS: The study included 200 sera obtained from dengue-suspected patients from 2006 to 2011...
2013: Virology Journal
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