Secreted complement regulatory protein clusterin interacts with dengue virus nonstructural protein 1

Kurosu, Takeshi; Chaichana, Panjaporn; Yamate, Masanobu; Anantapreecha, Surapee; Ikuta, Kazuyoshi

doi:10.1016/j.bbrc.2007.08.137

Cited by 94 publications

(74 citation statements)

References 25 publications

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“…Moreover, the nutritional status of children seems to have an impact on the risk of developing fatal DHF/DSS (57, 58). The NS1 lipoprotein particle also has in common with HDLs the ability to bind factors of the complement system (29)(30)(31)(32), and can thereby modulate host innate-immune response either as part of a viral escape mechanism or as a means to exacerbate inflammation (59,60).…”

Section: Discussionmentioning

confidence: 99%

“…Preincubation of hepatocytes with soluble NS1 enhances subsequent infection by a homologous strain of DENV (28). In addition, both soluble and cell-surface-associated NS1 are capable of modulating complement activation pathways through the formation of immune complexes or binding to host proteins, such as the regulatory protein factor H, complement factor C4, or clusterin (29)(30)(31)(32).…”

mentioning

confidence: 99%

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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%

mentioning

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

show abstract

“…After translation as a single polyprotein, it is cleaved by host and viral proteases to produce 3 structural (C, prM, and E) and 7 nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins (11,12). NS1 is a multifunctional glycoprotein that is involved in viral replication (13)(14)(15)(16) and modulation of the immune response (17)(18)(19)(20)(21)(22). The key role NS1 plays in RNA replication has been shown previously, with mutations or deletions in the NS1 gene resulting in a lack of detectable RNA replication.…”

mentioning

confidence: 99%

NS1′ Colocalizes with NS1 and Can Substitute for NS1 in West Nile Virus Replication

Young

Melian

Khromykh

2013

J Virol

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NS1= is a C-terminally extended form of the NS1 protein produced only by encephalitic flaviviruses from the Japanese encephalitis virus serogroup. Here we show that West Nile virus (WNV) NS1= and NS1 localize to the same cellular compartments when expressed from plasmid DNAs and also colocalize to viral RNA replication sites in infected cells. Using complementation analysis with NS1-deleted WNV cDNA, we demonstrated that NS1= is able to substitute for the crucial function of NS1 in virus replication. West Nile virus (WNV) is a mosquito-borne flavivirus within the Japanese encephalitis virus (JEV) serogroup. This serogroup also includes other encephalitic flaviviruses, such as JEV, Murray Valley encephalitis virus, and St. Louis encephalitis virus (1). The natural transmission cycle of WNV is between birds and mosquitoes, primarily the Culex species; however, it can cause incidental infections in humans. Since the outbreak of the more pathogenic WNV NY99 strain in New York in 1999 (2), WNV has emerged as a major cause of arboviral encephalitis in the United States (3). WNV strains can be divided into two distinct lineages, lineage 1 and lineage 2. Lineage 1 includes both WNV NY99 and Kunjin (WNV KUN ) (4), the prevalent strain within Australia (5). Despite high sequence similarity to the WNV NY99 strain (ϳ98% on the amino acid level) (6), most WNV KUN strains are highly attenuated, with only a small number of human infections and no fatalities reported (5, 7). Since its isolation in early 1960s, WNV KUN has been used extensively as a model for WNV infection (8, 9).The WNV KUN genome is a single-stranded positive-sense RNA of 11,022 nucleotides (10-12). After translation as a single polyprotein, it is cleaved by host and viral proteases to produce 3 structural (C, prM, and E) and 7 nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins (11,12). NS1 is a multifunctional glycoprotein that is involved in viral replication (13-16) and modulation of the immune response (17-22). The key role NS1 plays in RNA replication has been shown previously, with mutations or deletions in the NS1 gene resulting in a lack of detectable RNA replication. This function can be complemented in trans by the expression of NS1 (14, 15).An additional nonstructural protein, NS1=, is produced exclusively by the members of the JEV serogroup due to the presence of a Ϫ1 programmed ribosomal frameshift at the beginning of the adjacent NS2A gene (23)(24)(25). This frameshift, occurring in 30 to 50% of translation events (23,26), results in the formation of a 52-amino-acid C-terminally extended form of NS1. Although a role in neurovirulence has previously been demonstrated (23), no specific functions for NS1= in viral replication or virus-host interactions have been identified. In the present study, we show that the NS1= protein colocalizes with NS1 in viral RNA replication sites in the endoplasmic reticulum (ER) of infected cells and can substitute for the function of NS1 in viral replication.Plasmid DNA-derived expression of NS1 and NS...

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“…Nonstructural-1 (NS1) and pre-membrane (prM) proteins of dengue virus bind to clusterin (CLU). This association of clusterin with NS1 and PrM may free C7, so helping in the formation of terminal complement complex (TCC) [17]. In severe dengue infection large amounts of C3a have been detected, enlightening its role in dengue pathogenesis.…”

Section: Role Of Complement Activation In Dfmentioning

confidence: 99%

Dengue Virus: Host-Pathogen Interactions and Emerging Role of DNA Vaccines

Atif

Raheel

Imran

et al. 2016

JHVRV

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Dengue virus infections are a major cause of mortality and morbidity in Southeast Asia, South and Central America with 24'000 deaths annually. Two factors are accountable for the severe outcomes of Dengue Hemorrhagic Fever (DHF); one is the virulence of the virus and second is the cross-reactivity of various dengue serotypes with the immune system of the host. Rapid rise in the levels of various cytokines, particularly Tumor Necrosis Factor-alpha (TNF-α), Interleukin-2 (IL-2), Interleukin-6 (IL-6), Interleukin-8 (IL-8) have a major role in inducing distinctive clinical presentations of DHF. These range from simple plasma leakage to hemorrhagic problems and even shock. Another hallmark of DHF is the presence of cross reactive primary antibodies which produce an intense immune response in secondary infection resulting in immune mediated pathology seen in DHF. There have been many attempts made in the past for the development of a suitable vaccine for dengue fever. Vaccination using plasmid DNA against dengue fever is an active area of research. In this review the role of different cells in the multiplication of dengue virus and viral interactions with the immune system have been discussed. Special emphasis is given to the nature of DNA vaccines in general developmental efforts of a dengue fever vaccine.

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Secreted complement regulatory protein clusterin interacts with dengue virus nonstructural protein 1

Cited by 94 publications

References 25 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

NS1′ Colocalizes with NS1 and Can Substitute for NS1 in West Nile Virus Replication

Dengue Virus: Host-Pathogen Interactions and Emerging Role of DNA Vaccines

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