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Flavivirus NS1

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
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
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...
September 24, 2016: Virus Genes
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
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...
September 5, 2016: Acta Tropica
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
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
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
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...
2016: Nature Microbiology
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
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
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
W Clay Brown, David L Akey, Jamie R Konwerski, Jeffrey T Tarrasch, Georgios Skiniotis, Richard J Kuhn, Janet L Smith
The Zika virus, which has been implicated in an increase in neonatal microcephaly and Guillain-Barré syndrome, has spread rapidly through tropical regions of the world. The virulence protein NS1 functions in genome replication and host immune-system modulation. Here, we report the crystal structure of full-length Zika virus NS1, revealing an elongated hydrophobic surface for membrane association and a polar surface that varies substantially among flaviviruses.
September 2016: Nature Structural & Molecular Biology
Karin Stettler, Martina Beltramello, Diego A Espinosa, Victoria Graham, Antonino Cassotta, Siro Bianchi, Fabrizia Vanzetta, Andrea Minola, Stefano Jaconi, Federico Mele, Mathilde Foglierini, Mattia Pedotti, Luca Simonelli, Stuart Dowall, Barry Atkinson, Elena Percivalle, Cameron P Simmons, Luca Varani, Johannes Blum, Fausto Baldanti, Elisabetta Cameroni, Roger Hewson, Eva Harris, Antonio Lanzavecchia, Federica Sallusto, Davide Corti
Zika virus (ZIKV), a mosquito-borne flavivirus with homology to Dengue virus (DENV), has become a public health emergency. By characterizing memory lymphocytes from ZIKV-infected patients, we dissected ZIKV-specific and DENV-cross-reactive immune responses. Antibodies to nonstructural protein 1 (NS1) were largely ZIKV-specific and were used to develop a serological diagnostic tool. In contrast, antibodies against E protein domain I/II (EDI/II) were cross-reactive and, although poorly neutralizing, potently enhanced ZIKV and DENV infection in vitro and lethally enhanced DENV disease in mice...
August 19, 2016: Science
Henry Puerta-Guardo, Dustin R Glasner, Eva Harris
Dengue is the most prevalent arboviral disease in humans and a major public health problem worldwide. Systemic plasma leakage, leading to hypovolemic shock and potentially fatal complications, is a critical determinant of dengue severity. Recently, we and others described a novel pathogenic effect of secreted dengue virus (DENV) non-structural protein 1 (NS1) in triggering hyperpermeability of human endothelial cells in vitro and systemic vascular leakage in vivo. NS1 was shown to activate toll-like receptor 4 signaling in primary human myeloid cells, leading to secretion of pro-inflammatory cytokines and vascular leakage...
July 2016: PLoS Pathogens
Hong-Ru Chen, Yung-Chun Chuang, Yee-Shin Lin, Hsiao-Sheng Liu, Ching-Chuan Liu, Guey-Chuen Perng, Trai-Ming Yeh
Dengue virus (DENV) is the most common mosquito-borne flavivirus; it can either cause mild dengue fever or the more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). One of the characteristic features of DHF/DSS is vascular leakage; although DENV nonstructural protein 1 (NS1) has been proved to induce vascular leakage after binding to Toll-like receptor 4, the down-stream mechanism has not yet been fully understood. In the sera of DENV-infected patients, the concentrations of DENV NS1 and inflammatory cytokine macrophage migration inhibitory factor (MIF) are positively correlated with disease severity, but whether DENV NS1 induces vascular leakage through MIF secretion remains unknown...
July 2016: PLoS Neglected Tropical Diseases
Edson R A Oliveira, Ricardo B de Alencastro, Bruno A C Horta
The flavivirus non-structural protein 1 (NS1) is a conserved glycoprotein with as yet undefined biological function. This protein dimerizes when inside infected cells or associated to cell membranes but also forms lipid-associated hexamers when secreted to the extracellular space. A single amino acid substitution (P250L) is capable of preventing the dimerization of NS1 resulting in lower virulence and slower virus replication. In this work, based on molecular dynamics simulations of the dengue-2 virus NS1 [Formula: see text]-ladder monomer as a core model, we found that this mutation can induce several conformational changes that importantly affect critical monomer-monomer interactions...
September 2016: European Biophysics Journal: EBJ
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
Lance Turtle, Tanushka Bali, Gemma Buxton, Savita Chib, Sajesh Chan, Mohammed Soni, Mohammed Hussain, Heather Isenman, Prachi Fadnis, Manjunatha M Venkataswamy, Vishali Satishkumar, Penny Lewthwaite, Ayako Kurioka, Srinivasa Krishna, M Veera Shankar, Riyaz Ahmed, Ashia Begum, Vasanthapuram Ravi, Anita Desai, Sutee Yoksan, Stefan Fernandez, Christian B Willberg, Henrik N Kloverpris, Christopher Conlon, Paul Klenerman, Vijaya Satchidanandam, Tom Solomon
Japanese encephalitis (JE) virus (JEV) is an important cause of encephalitis in children of South and Southeast Asia. However, the majority of individuals exposed to JEV only develop mild symptoms associated with long-lasting adaptive immunity. The related flavivirus dengue virus (DENV) cocirculates in many JEV-endemic areas, and clinical data suggest cross-protection between DENV and JEV. To address the role of T cell responses in protection against JEV, we conducted the first full-breadth analysis of the human memory T cell response using a synthetic peptide library...
June 27, 2016: Journal of Experimental Medicine
Hao Song, Jianxun Qi, Joel Haywood, Yi Shi, George F Gao
The association of Zika virus (ZIKV) infections with microcephaly has resulted in an ongoing public-health emergency. Here we report the crystal structure of a C-terminal fragment of ZIKV nonstructural protein 1 (NS1), a major host-interaction molecule that functions in flaviviral replication, pathogenesis and immune evasion. Comparison with West Nile and dengue virus NS1 structures reveals conserved features but diverse electrostatic characteristics at host-interaction interfaces, thus possibly implying different modes of flavivirus pathogenesis...
May 2016: Nature Structural & Molecular Biology
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