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Flavivirus NS1

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https://www.readbyqxmd.com/read/28202375/generation-and-characterization-of-west-nile-pseudo-infectious-reporter-virus-for-antiviral-screening
#1
Hong-Lei Zhang, Han-Qing Ye, Cheng-Lin Deng, Si-Qing Liu, Pei-Yong Shi, Cheng-Feng Qin, Zhi-Ming Yuan, Bo Zhang
West Nile virus (WNV), a mosquito-borne flavivirus, is an important neurotropic human pathogen. As a biosafety level-3 (BSL-3) agent, WNV is strictly to BSL-3 laboratories for experimentations, thus greatly hindering the development of vaccine and antiviral drug. Here, we developed a novel pseudo-infectious WNV reporter virus expressing the Gaussia luciferase (Gluc). A stable 293TNS1 cell line expressing NS1 was selected for trans-supplying NS1 protein to support the replication of WNV-ΔNS1 virus and WNV-ΔNS1-Gluc reporter virus with large-fragment deletion of NS1...
February 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28198446/a-mutation-identified-in-neonatal-microcephaly-destabilizes-zika-virus-ns1-assembly-in-vitro
#2
Deping Wang, Cheng Chen, Shengnan Liu, Han Zhou, Kailin Yang, Qi Zhao, Xiaoyun Ji, Chen Chen, Wei Xie, Zefang Wang, Li-Zhi Mi, Haitao Yang
An unprecedented epidemic of Zika virus (ZIKV) infection had spread to South and Central America. ZIKV infection was recently confirmed by CDC (the Centers for Disease Control and Prevention) to cause neonatal microcephaly, which posed a significant public health emergency of international concern. No specific vaccines or drugs are currently available to fight ZIKV infection. ZIKV nonstructural protein 1 (NS1) plays an essential role in viral replication and immune evasion. We determined the crystal structure of ZIKV NS1172-352, which forms a head-to-head, symmetric dimer with a unique 14-stranded β-ladder conserved among flaviviruses...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196656/a-cdna-clone-launched-platform-for-high-yield-production-of-inactivated-zika-vaccine
#3
Yujiao Yang, Chao Shan, Jing Zou, Antonio E Muruato, Diniz Nunes Bruno, Barbosa de Almeida Medeiros Daniele, Pedro F C Vasconcelos, Shannan L Rossi, Scott C Weaver, Xuping Xie, Pei-Yong Shi
A purified inactivated vaccine (PIV) using the Zika virus (ZIKV) Puerto Rico strain PRVABC59 showed efficacy in monkeys, and is currently in a phase I clinical trial. High-yield manufacture of this PIV is essential for its development and vaccine access. Here we report an infectious cDNA clone-launched platform to maximize its yield. A single NS1 protein substitution (K265E) was identified to increase ZIKV replication on Vero cells (a cell line approved for vaccine production) for both Cambodian FSS13025 and Puerto Rico PRVABC59 strains...
February 6, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28094237/a-multiplex-microsphere-immunoassay-for-zika-virus-diagnosis
#4
Susan J Wong, Andrea Furuya, Jing Zou, Xuping Xie, Alan P Dupuis, Laura D Kramer, Pei-Yong Shi
Rapid and accurate diagnosis of infectious agents is essential for patient care, disease control, and countermeasure development. The present serologic diagnosis of Zika virus (ZIKV) infection relies mainly on IgM-capture ELISA which is confounded with the flaw of cross-reactivity among different flaviviruses. In this communication, we report a multiplex microsphere immunoassay (MIA) that captures the diagnostic power of viral envelope protein (that elicits robust, yet cross-reactive antibodies to other flaviviruses) and the differential power of viral nonstructural proteins NS1 and NS5 (that induce more virus-type specific antibodies)...
January 10, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28018746/identifying-candidate-targets-of-immune-responses-in-zika-virus-based-on-homology-to-epitopes-in-other-flavivirus-species
#5
Xiaojun Xu, Kerrie Vaughan, Daniela Weiskopf, Alba Grifoni, Michael S Diamond, Alessandro Sette, Bjoern Peters
INTRODUCTION: The current outbreak of Zika virus has resulted in a massive effort to accelerate the development of ZIKV-specific diagnostics and vaccines. These efforts would benefit greatly from the definition of the specific epitope targets of immune responses in ZIKV, but given the relatively recent emergence of ZIKV as a pandemic threat, few such data are available. METHODS: We used a large body of epitope data for other Flaviviruses that was available from the IEDB for a comparative analysis against the ZIKV proteome in order to project targets of immune responses in ZIKV...
November 15, 2016: PLoS Currents
https://www.readbyqxmd.com/read/28006649/serodiagnosis-of-zika-virus-zikv-infections-by-a-novel-ns1-based-elisa-devoid-of-cross-reactivity-with-dengue-virus-antibodies-a-multicohort-study-of-assay-performance-2015-to-2016
#6
Katja Steinhagen, Christian Probst, Christiane Radzimski, Jonas Schmidt-Chanasit, Petra Emmerich, Marjan van Esbroeck, Janke Schinkel, Martin P Grobusch, Abraham Goorhuis, Jens M Warnecke, Erik Lattwein, Lars Komorowski, Andrea Deerberg, Sandra Saschenbrecker, Winfried Stöcker, Wolfgang Schlumberger
Serological diagnosis of Zika virus (ZIKV) infections is challenging due to high cross-reactivity between flaviviruses. We evaluated the diagnostic performance of a novel anti-ZIKV ELISA based on recombinant ZIKV non-structural protein 1 (NS1). Assay sensitivity was examined using sera from 27 patients with reverse transcription (RT)-PCR-confirmed and 85 with suspected ZIKV infection. Specificity was analysed using sera from 1,015 healthy individuals. Samples from 252 patients with dengue virus (n = 93), West Nile virus (n = 34), Japanese encephalitis virus (n = 25), chikungunya virus (n = 19) or Plasmodium spp...
December 15, 2016: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/27805221/analysis-of-worldwide-sequence-mutations-in-zika-virus-proteins-e-ns1-ns3-and-ns5-from-a-structural-point-of-view
#7
C F Baez, V A Barel, A M T de Souza, C R Rodrigues, R B Varella, N Cirauqui
Zika virus (ZIKV) is an emergent arbovirus that has attracted attention in the last year as a possible causative agent of congenital malformation; it shows a remarkably increased microcephaly risk during otherwise healthy pregnancies. We present here an analysis of all ZIKV sequences available in Genbank up to April 2016, studying the mutations in the whole polyprotein and their possible structural implications for the proteins E, NS1, NS3 and NS5. This study suggests that microcephaly is not a consequence of any particular amino acid substitution but, conceivably, is a feature of ZIKV itself...
December 20, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27798151/secreted-ns1-protects-dengue-virus-from-mannose-binding-lectin-mediated-neutralization
#8
Somchai Thiemmeca, Chamaiporn Tamdet, Nuntaya Punyadee, Tanapan Prommool, Adisak Songjaeng, Sansanee Noisakran, Chunya Puttikhunt, John P Atkinson, Michael S Diamond, Alongkot Ponlawat, Panisadee Avirutnan
Flavivirus nonstructural protein 1 (NS1) is a unique secreted nonstructural glycoprotein. Although it is absent from the flavivirus virion, intracellular and extracellular forms of NS1 have essential roles in viral replication and the pathogenesis of infection. The fate of NS1 in insect cells has been more controversial, with some reports suggesting it is exclusively cell associated. In this study, we confirm NS1 secretion from cells of insect origin and characterize its physical, biochemical, and functional properties in the context of dengue virus (DENV) infection...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27746901/illustrating-and-homology-modeling-the-proteins-of-the-zika-virus
#9
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/27665517/the-capacitive-sensing-of-ns1-flavivirus-biomarker
#10
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...
January 15, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27665292/a-simple-method-for-developing-an-infectious-cdna-clone-of-japanese-encephalitis-virus
#11
Hao Zheng, Xuchen Zheng, Wu Tong, Fei Liu, Chao Liang, Tao Wang, Fei Gao, Liwei Li, Tongling Shan, Guoxin Li, Guangzhi Tong
Flavivirus cDNA clones frequently demonstrate genetic instability in transformed bacteria, which hampers the construction and manipulation of cDNAs for infectious flaviviruses. In this study, we developed a stable, full-length cDNA clone, pJEHEN, of a GI JEV strain HEN0701 using a medium-copy-number pBR322 vector and propagating cDNA clones at room temperature. The virus vJEHEN recovered from the infectious clone was indistinguishable from the parent virus HEN0701 with respect to plaque morphology, growth kinetics, and virulence characteristics...
February 2017: Virus Genes
https://www.readbyqxmd.com/read/27633257/a-serological-protein-microarray-for-detection-of-multiple-cross-reactive-flavivirus-infections-in-horses-for-veterinary-and-public-health-surveillance
#12
N B Cleton, K van Maanen, S A Bergervoet, N Bon, C Beck, G-J Godeke, S Lecollinet, R Bowen, D Lelli, N Nowotny, M P G Koopmans, C B E M Reusken
The genus Flavivirus in the family Flaviviridae includes some of the most important examples of emerging zoonotic arboviruses that are rapidly spreading across the globe. Japanese encephalitis virus (JEV), West Nile virus (WNV), St. Louis encephalitis virus (SLEV) and Usutu virus (USUV) are mosquito-borne members of the JEV serological group. Although most infections in humans are asymptomatic or present with mild flu-like symptoms, clinical manifestations of JEV, WNV, SLEV, USUV and tick-borne encephalitis virus (TBEV) can include severe neurological disease and death...
September 15, 2016: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/27609639/dengue-virus-surveillance-detection-of-denv-4-in-the-city-of-s%C3%A3-o-jos%C3%A3-do-rio-preto-sp-brazil
#13
Tatiana Elias Colombo, Danila Vedovello, Carolina Colombelli Pacca-Mazaro, Adriano Mondini, João Pessoa Araújo, Eliana Cabrera, José Carlos Lopes, Izalco Nuremberg Penha Dos Santos, Andréia Francesli Negri Reis, Fabiana Rodrigues Costa, Lilian Elisa Arão Antônio Cruz, Jurandir Ferreira, Eliseu Soares de Oliveira Rocha, Erna Geessien Kroon, Roberta Vieira de Morais Bronzoni, Nikos Vasilakis, Maurício Lacerda Nogueira
Dengue viruses are the most common arbovirus infection worldwide and are caused by four distinct serotypes of the dengue virus (DENV). In the present study, we assessed DENV transmission in São José do Rio Preto (SJRP) from 2010 to 2014. We analyzed blood samples from febrile patients who were attended at health care centers in SJRP. DENV detection was performed using multiplex RT-PCR, using flavivirus generic primers, based on the genes of the non-structural protein (NS5), followed by nested-PCR assay with species-specific primers...
December 2016: Acta Tropica
https://www.readbyqxmd.com/read/27604155/molecular-basis-of-antibody-mediated-neutralization-and-protection-against-flavivirus
#14
REVIEW
Lianpan Dai, Qihui Wang, Jianxun Qi, Yi Shi, Jinghua Yan, George F Gao
Antibody-mediated humoral immunity plays a pivotal role in flavivirus control. Neutralizing antibodies targeting viral envelope (E) protein, provide protection against flaviviruses in vivo but can also promote virus infection by antibody-dependent enhancement when antibodies are weakly neutralizing or in subneutralizing concentrations. The molecular basis for antibody-mediated virus neutralization can be revealed by structural studies of monoclonal antibodies complexed with the E protein or virion. In addition, the flavivirus non-structural protein NS1 can also induce host antibody production, and some of these antibodies can provide protection against virus challenge...
October 2016: IUBMB Life
https://www.readbyqxmd.com/read/27588756/nonstructural-proteins-are-preferential-positive-selection-targets-in-zika-virus-and-related-flaviviruses
#15
Manuela Sironi, Diego Forni, Mario Clerici, Rachele Cagliani
The Flavivirus genus comprises several human pathogens such as dengue virus (DENV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV). Although ZIKV usually causes mild symptoms, growing evidence is linking it to congenital birth defects and to increased risk of Guillain-Barré syndrome. ZIKV encodes a polyprotein that is processed to produce three structural and seven nonstructural (NS) proteins. We investigated the evolution of the viral polyprotein in ZIKV and in related flaviviruses (DENV, Spondweni virus, and Kedougou virus)...
September 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27578809/contribution-of-intertwined-loop-to-membrane-association-revealed-by-zika-virus-full-length-ns1-structure
#16
Xiaoying Xu, Hao Song, Jianxun Qi, Yuqian Liu, Haiyuan Wang, Chao Su, Yi Shi, George F Gao
The association of Zika virus (ZIKV) infections with microcephaly and neurological diseases has highlighted an emerging public health concern. Here, we report the crystal structure of the full-length ZIKV nonstructural protein 1 (NS1), a major host-interaction molecule that functions in flaviviral replication, pathogenesis, and immune evasion. Of note, a long intertwined loop is observed in the wing domain of ZIKV NS1, and forms a hydrophobic "spike", which can contribute to cellular membrane association. For different flaviviruses, the amino acid sequences of the "spike" are variable but their common characteristic is either hydrophobic or positively charged, which is a beneficial feature for membrane binding...
August 30, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27562253/flavivirus-ns1-protein-in-infected-host-sera-enhances-viral-acquisition-by-mosquitoes
#17
Jianying Liu, Yang Liu, Kaixiao Nie, Senyan Du, Jingjun Qiu, Xiaojing Pang, Penghua Wang, Gong Cheng
The arbovirus life cycle involves viral transfer between a vertebrate host and an arthropod vector, and acquisition of virus from an infected mammalian host by a vector is an essential step in this process. Here, we report that flavivirus nonstructural protein-1 (NS1), which is abundantly secreted into the serum of an infected host, plays a critical role in flavivirus acquisition by mosquitoes. The presence of dengue virus (DENV) and Japanese encephalitis virus NS1s in the blood of infected interferon-α and γ receptor-deficient mice (AG6) facilitated virus acquisition by their native mosquito vectors because the protein enabled the virus to overcome the immune barrier of the mosquito midgut...
June 20, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27553173/differential-cell-line-susceptibility-to-the-emerging-zika-virus-implications-for-disease-pathogenesis-non-vector-borne-human-transmission-and-animal-reservoirs
#18
Jasper Fuk-Woo Chan, Cyril Chik-Yan Yip, Jessica Oi-Ling Tsang, Kah-Meng Tee, Jian-Piao Cai, Kenn Ka-Heng Chik, Zheng Zhu, Chris Chung-Sing Chan, Garnet Kwan-Yue Choi, Siddharth Sridhar, Anna Jinxia Zhang, Gang Lu, Kin Chiu, Amy Cheuk-Yin Lo, Sai-Wah Tsao, Kin-Hang Kok, Dong-Yan Jin, Kwok-Hung Chan, Kwok-Yung Yuen
Zika virus (ZIKV) is unique among human-pathogenic flaviviruses by its association with congenital anomalies and trans-placental and sexual human-to-human transmission. Although the pathogenesis of ZIKV-associated neurological complications has been reported in recent studies, key questions on the pathogenesis of the other clinical manifestations, non-vector-borne transmission and potential animal reservoirs of ZIKV remain unanswered. We systematically characterized the differential cell line susceptibility of 18 human and 15 nonhuman cell lines to two ZIKV isolates (human and primate) and dengue virus type 2 (DENV-2)...
August 24, 2016: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/27512066/inhibition-of-the-membrane-attack-complex-by-dengue-virus-ns1-through-interaction-with-vitronectin-and-terminal-complement-proteins
#19
Jonas Nascimento Conde, Emiliana Mandarano da Silva, Diego Allonso, Diego Rodrigues Coelho, Iamara da Silva Andrade, Luciano Neves de Medeiros, Joice Lima Menezes, Angela Silva Barbosa, Ronaldo Mohana-Borges
: Dengue virus (DENV) infects millions of people worldwide and is a major public health problem. DENV nonstructural protein 1 (NS1) is a conserved glycoprotein that associates with membranes and is also secreted into the plasma in DENV-infected patients. The present study describes a novel mechanism by which NS1 inhibits the terminal complement pathway. We first identified the terminal complement regulator vitronectin (VN) as a novel DENV2 NS1 binding partner by using a yeast two-hybrid system...
November 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27473856/flavivirus-ns1-a-multifaceted-enigmatic-viral-protein
#20
REVIEW
Meghana Rastogi, Nikhil Sharma, Sunit Kumar Singh
Flaviviruses are emerging arthropod-borne viruses representing an immense global health problem. The prominent viruses of this group include dengue virus, yellow fever virus, Japanese encephalitis virus, West Nile virus tick borne encephalitis virus and Zika Virus. These are endemic in many parts of the world. They are responsible for the illness ranging from mild flu like symptoms to severe hemorrhagic, neurologic and cognitive manifestations leading to death. NS1 is a highly conserved non-structural protein among flaviviruses, which exist in diverse forms...
2016: Virology Journal
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