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Dengue, flavivirus

Stefan W Metz, Shaomin Tian, Gabriel Hoekstra, Xianwen Yi, Michelle Stone, Katie Horvath, Michael J Miley, Joseph DeSimone, Chris J Luft, Aravinda M de Silva
Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year. Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes...
October 2016: PLoS Neglected Tropical Diseases
Marie Louise Landry, Kirsten St George
CONTEXT: -The rapid and accurate diagnosis of Zika virus infection is an international priority. OBJECTIVE: -To review current recommendations, methods, limitations, and priorities for Zika virus testing. DATA SOURCES: -Sources include published literature, public health recommendations, laboratory procedures, and testing experience. CONCLUSIONS: -Until recently, the laboratory diagnosis of Zika infection was confined to public health or research laboratories that prepared their own reagents, and test capacity has been limited...
October 20, 2016: Archives of Pathology & Laboratory Medicine
Laura Rivino, Mei Qiu Lim
Dengue (DENV) and Zika viruses (ZIKV) are rapidly emerging mosquito-borne flaviviruses which represent a public health concern. Understanding host protective immunity to these viruses is critical for the design of optimal vaccines. Over a decade of research has highlighted a significant contribution of the T cell response to both protection and/or disease enhancement during dengue infection, the latter being mainly associated with sub-optimal cross-reactive T cell responses during secondary infections. Phase IIb/III clinical trials of the first licensed tetravalent dengue vaccine highlight increased vaccine efficacy in dengue-immune as opposed to dengue-naïve vaccinees, suggesting a possible immunoprotective role of pre-existing DENV-specific T cells that are boosted upon vaccination...
October 20, 2016: Immunology
B Mishra, B Behera
Until now, known as the demure cousin of dengue virus (DENV) inhabiting Africa, Zika virus (ZIKV) has reinvented itself to cause explosive epidemics captivating the Western hemisphere. The outbreak causing potential for ZIKV was realized when it made its way from Africa to Yap Island Micronesia in 2007, and in French Polynesia in 2013. From there, it moved on to Brazil in 2015. Now ZIKV has infected people in more than 33 countries in Central and South America and the Caribbean. Moreover the epidemiological and subsequent virological association with microcephaly cases in Brazil has prompted the World Health Organization to declare a public health emergency of International Concern...
October 2016: Journal of Postgraduate Medicine
Yuka Saito, Meng Ling Moi, Nozomi Takeshita, Chang-Kweng Lim, Hajime Shiba, Kuniaki Hosono, Masayuki Saijo, Ichiro Kurane, Tomohiko Takasaki
BACKGROUND: Dengue virus (DENV) and Japanese encephalitis virus (JEV) belong to the genus Flavivirus, and infection with a virus within this genus induces antibodies that are cross-reactive to other flaviviruses. Particularly in DENV infection, antibodies to DENV possess two competing activities: neutralizing activity and infection-enhancing activity. These antibody activities are considered central in modulating clinical outcomes of DENV infection. Here, we determined the neutralizing and infection-enhancing activity of DENV cross-reactive antibodies in adults before and after JE vaccination...
October 18, 2016: BMC Infectious Diseases
Edson R A Oliveira, Ronaldo Mohana-Borges, Ricardo B de Alencastro, Bruno A C Horta
Flaviviruses, such as dengue and zika viruses, are etiologic agents transmitted to humans mainly by arthropods and are of great epidemiological interest. The flavivirus capsid protein is a structural element required for the viral nucleocapsid assembly that presents the classical function of sheltering the viral genome. After decades of research, many reports have shown its different functionalities and influence over cell normal functioning. The subcellular distribution of this protein, which involves accumulation around lipid droplets and nuclear localization, also corroborates with its multi-functional characteristic...
October 14, 2016: Virus Research
Fatiha Benmansour, Iuni Trist, Bruno Coutard, Etienne Decroly, Gilles Querat, Andrea Brancale, Karine Barral
With the aim to help drug discovery against dengue virus (DENV), a fragment-based drug design approach was applied to identify ligands targeting a main component of DENV replication complex: the NS5 AdoMet-dependent mRNA methyltransferase (MTase) domain, playing an essential role in the RNA capping process. Herein, we describe the identification of new inhibitors developed using fragment-based, structure-guided linking and optimization techniques. Thermal-shift assay followed by a fragment-based X-ray crystallographic screening lead to the identification of three fragment hits binding DENV MTase...
October 5, 2016: European Journal of Medicinal Chemistry
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
Rupsa Basu, Ebenezer Tumban
Zika virus (ZIKV) is a mosquito-borne flavivirus that is transmitted through the bite of Aedes spp mosquitoes and less predominantly, through sexual intercourse. Prior to 2007, ZIKV was associated with only sporadic human infections with minimal or no clinical manifestations. Recently the virus has caused disease outbreaks from the Pacific Islands, the Americas, and off the coast of West Africa with approximately 1.62 million people suspected to be infected in more than 60 countries around the globe. The recent ZIKV outbreaks have been associated with guillain-barré syndrome, congenital syndrome (microcephaly, congenital central nervous system anomalies), miscarriages, and even death...
October 6, 2016: Virology Journal
Richard Hoyos-López, Juan Suaza-Vasco, Guillermo Rúa-Uribe, Sandra Uribe, Juan Carlos Gallego-Gómez
Arboviruses belonging to the genera Flavivirus and Alphavirus were detected in mosquitoes in a rural area of San Bernardo del Viento (Córdoba, Colombia). A total of 22,180 mosquitoes were collected, sorted into 2,102 pools, and tested by generic/nested reverse transcription-polymerase chain reaction. Venezuelan equine encephalitis virus, dengue virus, West Nile virus, St. Louis encephalitis virus, yellow fever virus, and Culex flavivirus were detected and identified by sequencing. The detection of arboviral pathogens in this zone represents possible circulation and indicates a human health risk, demonstrating the importance of virological surveillance activities...
October 3, 2016: Memórias do Instituto Oswaldo Cruz
Miguel A Martín-Acebes, Ángela Vázquez-Calvo, Juan-Carlos Saiz
Flaviviruses are emerging arthropod-borne pathogens that cause life-threatening diseases such as yellow fever, dengue, West Nile encephalitis, tick-borne encephalitis, Kyasanur Forest disease, tick-borne encephalitis, or Zika disease. This viral genus groups >50 viral species of small enveloped plus strand RNA virus that are phylogenetically closely related to hepatitis C virus. Importantly, the flavivirus life cycle is intimately associated to host cell lipids. Along this line, flaviviruses rearrange intracellular membranes from the endoplasmic-reticulum of the infected cells to develop adequate platforms for viral replication and particle biogenesis...
October 1, 2016: Progress in Lipid Research
Zhong-Yu Liu, Xiao-Feng Li, Tao Jiang, Yong-Qiang Deng, Qing Ye, Hui Zhao, Jiu-Yang Yu, Cheng-Feng Qin
Viral replicase recruitment and long-range RNA interactions are essential for RNA virus replication, yet the mechanism of their interplay remains elusive. Flaviviruses include numerous important human pathogens, e.g., dengue virus (DENV) and Zika virus (ZIKV). Here, we revealed a highly conserved, conformation-tunable cis-acting element named 5'-UAR-flanking stem (UFS) in the flavivirus genomic 5' terminus. We demonstrated that the UFS was critical for efficient NS5 recruitment and viral RNA synthesis in different flaviviruses...
October 1, 2016: ELife
Alex Michael Ward, Meredith E K Calvert, Leah R Read, Seokyoung Kang, Brandt E Levitt, George Dimopoulos, Shelton S Bradrick, Jayantha Gunaratne, Mariano A Garcia-Blanco
Dengue virus (DENV) is a mosquito-borne Flavivirus classified into four serotypes (DENV-1-4) that causes Dengue fever (DF), Dengue hemorrhagic Fever (DHF) or Dengue shock syndrome (DSS). An estimated 390 million people are at risk for infection with DENV and there are no effective vaccines or therapeutics. We utilized RNA chromatography coupled with quantitative mass spectrometry (qMS) to identify host RNA binding proteins (RBPs) that interact with DENV-2 RNA. We identified ERI3 (also PRNPIP and PINT1), a putative 3'-5' RNA exonuclease, which preferentially associates with DENV-2 genomic RNA via interactions with dumbbell structures in the 3' UTR...
September 29, 2016: Scientific Reports
Scott Goebel, Beth Snyder, Timothy Sellati, Mohammad Saeed, Roger Ptak, Michael Murray, Robert Bostwick, Jonathan Rayner, Fusataka Koide, Raj Kalkeri
Despite the rapid spread of Zika virus (ZIKV) infection and associated neurological complications in the America's, prophylactic or therapeutic countermeasures are not currently available. This is mostly due to the fact that until recently there was no presumed need for medical intervention since there was no association between ZIKV infection and significant human morbidity. Consequently, there are currently no tools due mostly to the lack of sensitive cell based assays amenable for identification of ZIKV inhibitors...
October 3, 2016: Journal of Virological Methods
Mariano A Garcia-Blanco, Subhash G Vasudevan, Shelton S Bradrick, Christopher Nicchitta
Upon release of the ∼11 kb single-stranded positive polarity dengue virus genomic RNA (gRNA) into the cytoplasm of an infected cell, it serves as the template for translation of the viral polyprotein, which is cleaved into three structural and seven non-structural proteins. The structural organization of the viral replication complex and RNA is not known but it is increasingly becoming evident that the viral gRNA and replication intermediates adopt unique structural features and localize to discrete regions in the infected cell...
October 2016: Antiviral Research
Juliana Cecchetto, Flávio C B Fernandes, Rute Lopes, Paulo R Bueno
NS1 is a biomarker for different Flavivirus diseases such as dengue (DENV), zika (ZIKV) and chikungunya (CHIKV) and was herein selectively quantified by electrochemical capacitive sensing (an impedance-derived capacitance methodology wherein the redox probe is contained in the receptive layer) mainly aiming dengue diagnosis in phosphate buffer saline and blood serum environments (up to the neat level). The capacitive sensing was compared to traditional concurrent impedimetric approach (in which the redox probe is added in the biological solution) and other transient methods stated in the literature regarding figures of merit such as limit of detection, linear range, relative standard deviation and affinity constant...
August 30, 2016: Biosensors & Bioelectronics
Anu Susan Charles, Rebecca C Christofferson
INTRODUCTION: Zika virus (ZIKV) has emerged in dengue (DENV) endemic areas, where these two related flaviviruses continue to co-circulate. DENV is a complex of four serotypes and infections can progress to severe disease. It is thought that this is mediated by antibody dependent enhancement (ADE) whereby antibodies from a primary DENV infection are incapable of neutralizing heterologous DENV infections with another serotype. ADE has been demonstrated among other members of the Flavivirus group...
2016: PLoS Currents
Delia Tarantino, Rolando Cannalire, Eloise Mastrangelo, Romina Croci, Gilles Querat, Maria Letizia Barreca, Martino Bolognesi, Giuseppe Manfroni, Violetta Cecchetti, Mario Milani
RNA dependent RNA polymerases (RdRp) are essential enzymes for flavivirus replication. Starting from an in silico docking analysis we identified a pyridobenzothiazole compound, HeE1-2Tyr, able to inhibit West Nile and Dengue RdRps activity in vitro, which proved effective against different flaviviruses in cell culture. Crystallographic data show that HeE1-2Tyr binds between the fingers domain and the priming loop of Dengue virus RdRp (Site 1). Conversely, enzyme kinetics, binding studies and mutational analyses suggest that, during the catalytic cycle and assembly of the RdRp-RNA complex, HeE1-2Tyr might be hosted in a distinct binding site (Site 2)...
October 2016: Antiviral Research
Vaishali P Waman, Pandurang Kolekar, Mukund R Ramtirthkar, Mohan M Kale, Urmila Kulkarni-Kale
BACKGROUND: Dengue is one of the most common arboviral diseases prevalent worldwide and is caused by Dengue viruses (genus Flavivirus, family Flaviviridae). There are four serotypes of Dengue Virus (DENV-1 to DENV-4), each of which is further subdivided into distinct genotypes. DENV-2 is frequently associated with severe dengue infections and epidemics. DENV-2 consists of six genotypes such as Asian/American, Asian I, Asian II, Cosmopolitan, American and sylvatic. Comparative genomic study was carried out to infer population structure of DENV-2 and to analyze the role of evolutionary and spatiotemporal factors in emergence of diversifying lineages...
2016: PeerJ
Moon Y F Tay, Kate Smith, Ivan H W Ng, Kitti W K Chan, Yongqian Zhao, Eng Eong Ooi, Julien Lescar, Dahai Luo, David A Jans, Jade K Forwood, Subhash G Vasudevan
Dengue virus NS5 is the most highly conserved amongst the viral non-structural proteins and is responsible for capping, methylation and replication of the flavivirus RNA genome. Interactions of NS5 with host proteins also modulate host immune responses. Although replication occurs in the cytoplasm, an unusual characteristic of DENV2 NS5 is that it localizes to the nucleus during infection with no clear role in replication or pathogenesis. We examined NS5 of DENV1 and 2, which exhibit the most prominent difference in nuclear localization, employing a combination of functional and structural analyses...
September 2016: PLoS Pathogens
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