Evidence that the mature form of the flavivirus nonstructural protein NS1 is a dimer

Winkler, Günther; Randolph, Valerie B.; Cleaves, Graham R.; Ryan, Terence E.; Stollar, Victor

doi:10.1016/0042-6822(88)90408-4

Cited by 209 publications

(206 citation statements)

References 32 publications

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“…Virus-infected Vero cells were found to secrete the viral structural proteins, E, C and M (the latter two migrating near the electrophoretic front) as well as the dimeric form of the non-structural-1 protein (NS1)2. These results are similar to those reported using BHK cells infected with DEN-2 (Winkler et al, 1988). In contrast, DEN-4-infected C6/36 cells secreted only viral structural proteins, but no form of the NS1.…”

Section: Correlation Of E Protein Binding With Cell Susceptibility Tosupporting

confidence: 80%

Correlation of E protein binding with cell susceptibility to dengue 4 virus infection

Anderson

King

Innis

1992

Journal of General Virology

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Section: Correlation Of E Protein Binding With Cell Susceptibility Tosupporting

confidence: 80%

Correlation of E protein binding with cell susceptibility to dengue 4 virus infection

Anderson

King

Innis

1992

Journal of General Virology

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“…NS1, a glycoprotein of approximately 40K to 50K, is expressed on the surface of virus-infected cells (Gould et al, 1985) and is secreted by infected Vero, but not C6/36 cells (Mason, 1989). The NSI protein exists primarily as a homodimer of approximately 90K which can be denatured to form a monomer of approximately 45K (Winkler et al, 1988). The role of NS1 in viral replication is as yet unknown.…”

Section: Introductionmentioning

confidence: 99%

Epitope Analysis of the Envelope and Non-structural Glycoproteins of Murray Valley Encephalitis Virus

Hall

Kay

Burgess

et al. 1990

Journal of General Virology

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Previous studies have shown that antibodies produced against strategic flavivirus epitopes play an important role in recovery and immunity. Definition of the conformation and location of these epitopes and the degree of their conservation among flaviviruses is important to understanding the humoral response to flavivirus infection. In this study we have examined epitopes recognized by 14 monoclonal antibodies (MAbs) produced to the envelope (E) and nonstructural (NS1) proteins of Murray Valley encephalitis virus (MVE). These antibodies were analysed for specificity, neutralization, haemagglutination inhibition (HI) and competitive binding. We have identified six distinct epitopes on the E protein which are located in four non-overlapping domains. MAbs to epitopes in one domain neutralized virus, were specific for MVE and Japanese encephalitis virus, and reacted with epitopes resistant to reduction. Two other E domains, one specific to MVE and the other shared by all flaviviruses, also contained neutralization sites and were stabilized by disulphide bonds. The fourth domain on E was conserved among the flaviviruses, sensitive to SDS denaturation and did not induce neutralizing antibody. Studies with MVE NS 1 MAbs revealed that they were mostly type-specific, unreactive with conserved epitopes, and unreactive in HI and neutralization tests. The six epitopes identified on NS 1 did not overlap and represent antigenic domains either resistant or sensitive to reduction. Immunoblotting of viral proteins in MVE-infected C6/36 cells revealed two distinct forms of NS1 and high Mr proteins of 97K and 108K that represented disulphide-linked heterodimers of E and NS1.

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“…The protein, possibly modified by GPI, also associates to lipid rafts at the plasma membrane and mediates a signaling pattern common to GPI-anchored proteins in the presence of specific antibodies (17)(18)(19). NS1 is eventually secreted by DENV-infected mammalian cells (20)(21)(22) and released in the blood stream of infected individuals (23,24). The protein is detectable in plasma from the onset of fever up to the first days of convalescence at concentrations that can exceed several micrograms per milliliter (23)(24)(25).…”

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

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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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Evidence that the mature form of the flavivirus nonstructural protein NS1 is a dimer

Cited by 209 publications

References 32 publications

Correlation of E protein binding with cell susceptibility to dengue 4 virus infection

Correlation of E protein binding with cell susceptibility to dengue 4 virus infection

Epitope Analysis of the Envelope and Non-structural Glycoproteins of Murray Valley Encephalitis Virus

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

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