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Flavivirus nonstructural protein 1

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https://www.readbyqxmd.com/read/27798151/secreted-ns1-protects-dengue-virus-from-mannose-binding-lectin-mediated-neutralization
#1
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/27578809/contribution-of-intertwined-loop-to-membrane-association-revealed-by-zika-virus-full-length-ns1-structure
#2
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
#3
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
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
#4
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
#5
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/27409803/dengue-virus-nonstructural-protein-1-induces-vascular-leakage-through-macrophage-migration-inhibitory-factor-and-autophagy
#6
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
https://www.readbyqxmd.com/read/27088990/zika-virus-ns1-structure-reveals-diversity-of-electrostatic-surfaces-among-flaviviruses
#7
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
https://www.readbyqxmd.com/read/27068162/glycosylation-of-dengue-virus-glycoproteins-and-their-interactions-with-carbohydrate-receptors-possible-targets-for-antiviral-therapy
#8
REVIEW
Fakhriedzwan Idris, Siti Hanna Muharram, Suwarni Diah
Dengue virus, an RNA virus belonging to the genus Flavivirus, affects 50 million individuals annually, and approximately 500,000-1,000,000 of these infections lead to dengue hemorrhagic fever or dengue shock syndrome. With no licensed vaccine or specific antiviral treatments available to prevent dengue infection, dengue is considered a major public health problem in subtropical and tropical regions. The virus, like other enveloped viruses, uses the host's cellular enzymes to synthesize its structural (C, E, and prM/M) and nonstructural proteins (NS1-5) and, subsequently, to glycosylate these proteins to produce complete and functional glycoproteins...
July 2016: Archives of Virology
https://www.readbyqxmd.com/read/26807734/surveillance-for-western-equine-encephalitis-st-louis-encephalitis-and-west-nile-viruses-using-reverse-transcription-loop-mediated-isothermal-amplification
#9
Sarah S Wheeler, Cameron S Ball, Stanley A Langevin, Ying Fang, Lark L Coffey, Robert J Meagher
Collection of mosquitoes and testing for vector-borne viruses is a key surveillance activity that directly influences the vector control efforts of public health agencies, including determining when and where to apply insecticides. Vector control districts in California routinely monitor for three human pathogenic viruses including West Nile virus (WNV), Western equine encephalitis virus (WEEV), and St. Louis encephalitis virus (SLEV). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) offers highly sensitive and specific detection of these three viruses in a single multiplex reaction, but this technique requires costly, specialized equipment that is generally only available in centralized public health laboratories...
2016: PloS One
https://www.readbyqxmd.com/read/26659204/establishment-of-an-algorithm-using-prm-e-and-ns1-specific-igm-antibody-capture-enzyme-linked-immunosorbent-assays-in-diagnosis-of-japanese-encephalitis-virus-and-west-nile-virus-infections-in-humans
#10
Jedhan U Galula, Gwong-Jen J Chang, Shih-Te Chuang, Day-Yu Chao
The front-line assay for the presumptive serodiagnosis of acute Japanese encephalitis virus (JEV) and West Nile virus (WNV) infections is the premembrane/envelope (prM/E)-specific IgM antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA). Due to antibody cross-reactivity, MAC-ELISA-positive samples may be confirmed with a time-consuming plaque reduction neutralization test (PRNT). In the present study, we applied a previously developed anti-nonstructural protein 1 (NS1)-specific MAC-ELISA (NS1-MAC-ELISA) on archived acute-phase serum specimens from patients with confirmed JEV and WNV infections and compared the results with prM/E containing virus-like particle-specific MAC-ELISA (VLP-MAC-ELISA)...
February 2016: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/26559836/the-c-terminus-of-the-core-%C3%AE-ladder-domain-in-japanese-encephalitis-virus-nonstructural-protein-1-is-flexible-for-accommodation-of-heterologous-epitope-fusion
#11
Li-Chen Yen, Jia-Teh Liao, Hwei-Jen Lee, Wei-Yuan Chou, Chun-Wei Chen, Yi-Ling Lin, Ching-Len Liao
UNLABELLED: NS1 is the only nonstructural protein that enters the lumen of the endoplasmic reticulum (ER), where NS1 is glycosylated, forms a dimer, and is subsequently secreted during flavivirus replication as dimers or hexamers, which appear to be highly immunogenic to the infected host, as protective immunity can be elicited against homologous flavivirus infections. Here, by using a trans-complementation assay, we identified the C-terminal end of NS1 derived from Japanese encephalitis virus (JEV), which was more flexible than other regions in terms of housing foreign epitopes without a significant impact on virus replication...
February 2016: Journal of Virology
https://www.readbyqxmd.com/read/26355030/dengue-virus-ns1-triggers-endothelial-permeability-and-vascular-leak-that-is-prevented-by-ns1-vaccination
#12
P Robert Beatty, Henry Puerta-Guardo, Sarah S Killingbeck, Dustin R Glasner, Kaycie Hopkins, Eva Harris
The four dengue virus serotypes (DENV1 to DENV4) are mosquito-borne flaviviruses that cause up to ~100 million cases of dengue annually worldwide. Severe disease is thought to result from immunopathogenic processes involving serotype cross-reactive antibodies and T cells that together induce vasoactive cytokines, causing vascular leakage that leads to shock. However, no viral proteins have been directly implicated in triggering endothelial permeability, which results in vascular leakage. DENV nonstructural protein 1 (NS1) is secreted and circulates in patients' blood during acute infection; high levels of NS1 are associated with severe disease...
September 9, 2015: Science Translational Medicine
https://www.readbyqxmd.com/read/25964384/conserved-rna-secondary-structures-and-long-range-interactions-in-hepatitis-c-viruses
#13
Markus Fricke, Nadia Dünnes, Margarita Zayas, Ralf Bartenschlager, Michael Niepmann, Manja Marz
Hepatitis C virus (HCV) is a hepatotropic virus with a plus-strand RNA genome of ∼9.600 nt. Due to error-prone replication by its RNA-dependent RNA polymerase (RdRp) residing in nonstructural protein 5B (NS5B), HCV isolates are grouped into seven genotypes with several subtypes. By using whole-genome sequences of 106 HCV isolates and secondary structure alignments of the plus-strand genome and its minus-strand replication intermediate, we established refined secondary structures of the 5' untranslated region (UTR), the cis-acting replication element (CRE) in NS5B, and the 3' UTR...
July 2015: RNA
https://www.readbyqxmd.com/read/25614585/last-20-aa-of-the-west-nile-virus-ns1-protein-are-responsible-for-its-retention-in-cells-and-the-formation-of-unique-heat-stable-dimers
#14
Lucy B Young, Ezequiel Balmori Melian, Yin Xiang Setoh, Paul R Young, Alexander A Khromykh
West Nile virus (WNV), a mosquito-borne flavivirus, is the major cause of arboviral encephalitis in the USA. As with other members of the Japanese encephalitis virus serogroup, WNV produces an additional non-structural protein, NS1', a C-terminal extended product of NS1 generated as the result of a -1 programmed ribosomal frameshift (PRF). We have previously shown that mutations abolishing the PRF, and consequently NS1', resulted in reduced neuroinvasiveness. However, whether this was caused by the PRF event itself or by the lack of a PRF product, NS1', or a combination of both, remains undetermined...
May 2015: Journal of General Virology
https://www.readbyqxmd.com/read/25502522/nonstructural-protein-1-specific-immunoglobulin-m-and-g-antibody-capture-enzyme-linked-immunosorbent-assays-in-diagnosis-of-flaviviral-infections-in-humans
#15
COMPARATIVE STUDY
Day-Yu Chao, Jedhan Ucat Galula, Wen-Fan Shen, Brent S Davis, Gwong-Jen J Chang
IgM antibody- and IgG antibody-capture enzyme-linked immunosorbent assays (MAC/GAC-ELISAs) targeted at envelope protein (E) of dengue viruses (DENV), West Nile virus, and Japanese encephalitis virus (JEV) are widely used as serodiagnostic tests for presumptive confirmation of viral infection. Antibodies directed against the flavivirus nonstructural protein 1 (NS1) have been proposed as serological markers of natural infections among vaccinated populations. The aim of the current study is to optimize an IgM and IgG antibody-capture ELISA (MAC/GAC-ELISA) to detect anti-NS1 antibodies and compare it with anti-E MAC/GAC-ELISA...
February 2015: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/25286855/use-of-massively-multiple-merged-data-for-low-resolution-s-sad-phasing-and-refinement-of-flavivirus-ns1
#16
David L Akey, W Clay Brown, Jamie R Konwerski, Craig M Ogata, Janet L Smith
An emergent challenge in macromolecular crystallography is the identification of the substructure from native anomalous scatterers in crystals that diffract to low to moderate resolution. Increasing the multiplicity of data sets has been shown to make previously intractable phasing problems solvable and to increase the useful resolution in model refinement. For the West Nile virus nonstructural protein 1 (NS1), a protein of novel fold, the utility of exceptionally high multiplicity data is demonstrated both in solving the crystal structure from the anomalous scattering of the native S atoms and in extending the useful limits of resolution during refinement...
October 2014: Acta Crystallographica. Section D, Biological Crystallography
https://www.readbyqxmd.com/read/25046112/japanese-encephalitis-virus-replication-is-negatively-regulated-by-autophagy-and-occurs-on-lc3-i-and-edem1-containing-membranes
#17
Manish Sharma, Sankar Bhattacharyya, Minu Nain, Manpreet Kaur, Vikas Sood, Vishal Gupta, Renu Khasa, Malik Z Abdin, Sudhanshu Vrati, Manjula Kalia
Autophagy is a lysosomal degradative pathway that has diverse physiological functions and plays crucial roles in several viral infections. Here we examine the role of autophagy in the life cycle of JEV, a neurotropic flavivirus. JEV infection leads to induction of autophagy in several cell types. JEV replication was significantly enhanced in neuronal cells where autophagy was rendered dysfunctional by ATG7 depletion, and in Atg5-deficient mouse embryonic fibroblasts (MEFs), resulting in higher viral titers...
September 2014: Autophagy
https://www.readbyqxmd.com/read/24889229/abrogation-of-tlr3-inhibition-by-discrete-amino-acid-changes-in-the-c-terminal-half-of-the-west-nile-virus-ns1-protein
#18
Clayton R Morrison, Frank Scholle
West Nile virus (WNV) is a mosquito-transmitted pathogen, which causes significant disease in humans. The innate immune system is a first-line defense against invading microorganism and many flaviviruses, including WNV, have evolved multifunctional proteins, which actively suppress its activation and antiviral actions. The WNV non-structural protein 1 (NS1) inhibits signal transduction originating from Toll-like receptor 3 (TLR3) and also critically contributes to virus genome replication. In this study we developed a novel FACS-based screen to attempt to separate these two functions...
May 2014: Virology
https://www.readbyqxmd.com/read/24631788/comprehensive-mapping-of-a-novel-ns1-epitope-conserved-in-flaviviruses-within-the-japanese-encephalitis-virus-serocomplex
#19
Rong-Hong Hua, Li-Ke Liu, Hong Huo, Ye-Nan Li, Li-Ping Guo, Xiao-Lei Wang, Cheng-Feng Qin, Zhi-Gao Bu
Nonstructural protein-1 (NS1) of the Japanese encephalitis virus (JEV) is an immunogenic protein that is a potential candidate for the development of vaccines and diagnostic reagents. NS1 is known to be more specific than the E protein in serological testing of flavivirus infections. However, NS1 exhibits cross-reactivity among flaviviruses even within the same genus and more so within a serocomplex. However, the cross-reactive epitopes on JEV NS1 are poorly characterized. The present study describes the full mapping of a linear B-cell epitope that is common and specific to the JEV serocomplex of Flaviviridae...
June 24, 2014: Virus Research
https://www.readbyqxmd.com/read/24594604/structural-basis-of-flavivirus-ns1-assembly-and-antibody-recognition
#20
Melissa A Edeling, Michael S Diamond, Daved H Fremont
The Flavivirus nonstructural protein 1 (NS1) is a conserved, membrane-associated and secreted glycoprotein with replication and immune evasion functions. Secreted NS1 is a hexameric, barrel-shaped lipoprotein that can bind back to the plasma membrane of cells. Antibodies targeting cell surface-associated NS1 can be protective in vivo in a manner dependent on Fc effector functions. We describe here the crystal structure of a C-terminal fragment (residues 172-352) of West Nile (WNV) and Dengue virus NS1 proteins at 1...
March 18, 2014: Proceedings of the National Academy of Sciences of the United States of America
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