Newly synthesized dengue-2 virus nonstructural protein NS1 is a soluble protein but becomes partially hydrophobic and membrane-associated after dimerization

Winkler, Günther; Maxwell, Stephen E.; Ruemmler, Christine; Stollar, Victor

doi:10.1016/0042-6822(89)90544-8

Cited by 216 publications

(214 citation statements)

References 20 publications

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“…Because recombinant NS1, lacking the putative GPIanchor signal present in the downstream NS2A coding region (17,19), shows no difference in lipid-binding capacity in comparison with native NS1, a GPI modification cannot account for NS1 attachment to membranes. Early studies following the folding process of NS1 in the endoplasmic reticulum (ER) indicated that the NS1 monomer is water-soluble and becomes membraneassociated once the protein dimerizes (44). We propose that lipidbinding sites form during the dimerization process itself, possibly Data are expressed in nanomoles.…”

Section: Discussionmentioning

confidence: 99%

Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein

Gutsche

Coulibaly

Voss

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

270

294

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Dengue virus (DENV) causes the major arboviral disease of the tropics, characterized in its severe forms by signs of hemorrhage and plasma leakage. DENV encodes a nonstructural glycoprotein, NS1, that associates with intracellular membranes and the cell surface. NS1 is eventually secreted as a soluble hexamer from DENV-infected cells and circulates in the bloodstream of infected patients. Extracellular NS1 has been shown to modulate the complement system and to enhance DENV infection, yet its structure and function remain essentially unknown. By combining cryoelectron microscopy analysis with a characterization of NS1 amphipathic properties, we show that the secreted NS1 hexamer forms a lipoprotein particle with an open-barrel protein shell and a prominent central channel rich in lipids. Biochemical and NMR analyses of the NS1 lipid cargo reveal the presence of triglycerides, bound at an equimolar ratio to the NS1 protomer, as well as cholesteryl esters and phospholipids, a composition evocative of the plasma lipoproteins involved in vascular homeostasis. This study suggests that DENV NS1, by mimicking or hijacking lipid metabolic pathways, contributes to endothelium dysfunction, a key feature of severe dengue disease.arbovirus | dengue hemorrhagic fever | amphiphilic proteins | secretion

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Section: Discussionmentioning

confidence: 99%

Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein

Gutsche

Coulibaly

Voss

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

270

294

View full text Add to dashboard Cite

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“…Dengue NS1 is a highly conserved 46-kDa nonstructural glycoprotein that both exists as an intracellular, membraneassociated and as an extracellular form secreted from DENVinfected mammalian cells (Winkler et al 1989). Clinical observations have shown that dengue NS1 antigen can be detected in the circulation during DENV infection and it elicits a specific immune response (Monath and Heonz 1996).…”

Section: Vector-borne and Zoonotic Diseasesmentioning

confidence: 99%

Evaluation of Nonstructural 1 Antigen Assays for the Diagnosis and Surveillance of Dengue in Singapore

Pok

Lai

Sng

et al. 2010

Vector-Borne and Zoonotic Diseases

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Early and accurate diagnosis of dengue is imperative for disease surveillance, which helps in the control of dengue in endemic countries. In this study, we evaluated the performance of three commercially available dengue nonstructural 1 (NS1) antigen assays (Bio-Rad PlateliaÔ Dengue NS1 Antigen ELISA, PanBio Dengue Early ELISA, and Bio-Rad Dengue NS1 Antigen Strip test) and compared them with reverse-transcription polymerase chain reaction (RT-PCR) and other commercially available serological assays for the diagnosis of dengue. The analysis showed RT-PCR to be the most sensitive and specific (100%) diagnostic method during the first 3 days of fever. The overall sensitivity of dengue NS1 antigen assays within the same period was 81.7%, indicating their potential role as a cost-effective and convenient alternative method to RT-PCR for the diagnosis of dengue fever in a primary healthcare setting. However, reduced sensitivity in detecting secondary dengue infections was one of the drawbacks of dengue NS1 antigen assays. Nonetheless, it remains a useful assay for the early detection of dengue and hence could play an important role in routine surveillance efforts to control dengue outbreaks in Singapore.

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“…It is a glycoprotein of 354 amino acids. In the host cell, the NS1 protein is expressed in three forms: an endoplasmic reticulum (ER)-resident form, a membrane-anchored form, and a secreted form (sNS1) (Winkler et al, 1989;Welsch et al, 2009), the latter being responsible for this observed anti-NS1 antibody production.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of B cell epitopes of dengue virus NS1 protein using bioinformatics approach

Pushpakumara¹,

Premarathne²,

Goonasekara³

2016

J. Natn. Sci. Foundation Sri Lanka

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Linear B cell epitopes of the dengue virus nonstructural protein 1 (NS1) were predicted using three B cell epitope prediction tools, Ellipro, Bepipred and SVMTrip. Fifty sequences from each dengue serotype, representing a wide geographic area and a time span, were aligned using MEGA 6 software. The predictions were evaluated by comparing the results among the three tools and with currently available data on assay positive immunogenic epitopes of dengue NS1. A total of 22 regions on the NS1 protein ranging 6 to 21 amino acids in size were predicted as epitopes with a high probability score by the three prediction tools. Many were found to be predicted as epitopes by more than one tool, showing a good agreement in the predictions by the three tools. Further, many of the epitopes overlapped with, or partially constituted regions on the NS1 protein, which have by various biochemical assays. Each of the 22 epitopes and the whole NS1 protein were then characterised for their percentages of conservation and phylogenetic relationship among and within each dengue serotypes, using IEDB and MEGA 6 analysis tools. Three epitopes were found to be highly conserved within the serotype but highly variable among the 04 dengue serotypes, suggesting that they could be used as possible among the four dengue serotypes, showing a potential use as B cell epitopes of dengue NS1 with therapeutic potential. B cell epitopes, bioinformatics, dengue, NS1 protein, phylogenetics. INTRODUCTIONDengue is one of the major public health concerns worldwide. Over 2.5 billion people, almost over 40 % of the world's population are at risk from dengue. The World Health Organisation (WHO) currently estimates that there may be 50 -100 million dengue infections worldwide every year. The number of cases is increasing and the disease is also spreading to new areas (Guzman et al., 2010). Developing a vaccine against dengue has been challenging, one reason being due to cross immunity to other dengue serotypes leading to enhancement of the disease upon subsequent infections (Thisyakorn & Dengvaxia, a live attenuated tetravalent chimeric vaccine, USA, was registered for use in endemic areas. After assessment for its safety, the WHO Strategic Advisory Group of Experts on Immunisation has recommended its vaccination in countries with high endemicity at national or subnational level. Its recommendation for immunisation is currently under assessment by the WHO (http://www.who.int/immunization/research/development/ dengue_vaccines/en/).The dengue virus has a genome of approximately 11,000 bases that encodes a single large polyprotein, which is subsequently cleaved into several structural and non-structural mature peptides. The polyprotein 418 P.D. Pushpakumara et al.

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Newly synthesized dengue-2 virus nonstructural protein NS1 is a soluble protein but becomes partially hydrophobic and membrane-associated after dimerization

Cited by 216 publications

References 20 publications

Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein

Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein

Evaluation of Nonstructural 1 Antigen Assays for the Diagnosis and Surveillance of Dengue in Singapore

Characterisation of B cell epitopes of dengue virus NS1 protein using bioinformatics approach

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