Pre-NS1 folds and is N-glycosylated

Stable Identifier
R-HSA-9919011
Type
Reaction [uncertain]
Species
Homo sapiens
Related Species
Dengue virus type 2
Compartment
ReviewStatus
5/5
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Pre-NS1 protein, while being folded, is glycosylated at Asn-130 and Asn-207 (Asn-905 and Asn-982 in the polyprotein, respectively). This process involves the alpha-glucosidase activity of the oligosaccharyltransferase (OST) complex, which initially adds high-mannose precursor glycans to these sites, followed by α-glucosidase trimming. In mature secreted NS1, the glycan at Asn-130 is typically processed to a complex glycan type, while Asn-207 retains high-mannose glycans (Prior & Wright, 1994; Somnuke et al., 2011; Wang et al., 2019; Hafirassou et al., 2017; reviewed in Idris et al., 2016; Yap et al., 2017; Feng et al., 2022). The chaperone HSPA5 (GRP78) is required for folding of glycosylated NS1 (Songprakhon et al., 2018; Denolly et al., 2023). Other chaperones binding to NS1 include calnexin (CALX), calreticulin (CALR), and the protein disulfide isomerases 1 (P4HB, PDIA1), and 3 (PDIA3) (Hafirassou et al., 2017; Denolly et al., 2023).
Literature References
PubMed ID Title Journal Year
29845540 Mechanisms of Antiviral Activity of Iminosugars Against Dengue Virus

Miller, JL, Tyrrell, BE, Zitzmann, N

Adv Exp Med Biol 2018
35436420 Glycosylation of viral proteins: Implication in virus-host interaction and virulence

Feng, T, Zhang, J, Chen, Z, Pan, W, Chen, Z, Yan, Y, Dai, J

Virulence 2022
31356638 Endocytosis of flavivirus NS1 is required for NS1-mediated endothelial hyperpermeability and is abolished by a single N-glycosylation site mutation

Wang, C, Puerta-Guardo, H, Biering, SB, Glasner, DR, Tran, EB, Patana, M, Gomberg, TA, Malvar, C, Lo, NTN, Espinosa, DA, Harris, E

PLoS Pathog 2019
24877997 Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial

Low, JG, Sung, C, Wijaya, L, Wei, Y, Rathore, APS, Watanabe, S, Tan, BH, Toh, L, Chua, LT, Hou, Y, Chow, A, Howe, S, Chan, WK, Tan, KH, Chung, JS, Cherng, BP, Lye, DC, Tambayah, PA, Ng, LC, Connolly, J, Hibberd, ML, Leo, YS, Cheung, YB, Ooi, EE, Vasudevan, SG

Lancet Infect Dis 2014
21429549 N-linked glycosylation of dengue virus NS1 protein modulates secretion, cell-surface expression, hexamer stability, and interactions with human complement

Somnuke, P, Hauhart, RE, Atkinson, JP, Diamond, MS, Avirutnan, P

Virology 2011
29281836 A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors

Hafirassou, ML, Meertens, L, Umana-Diaz, C, Labeau, A, Dejarnac, O, Bonnet-Madin, L, Kümmerer, BM, Delaugerre, C, Roingeard, P, Vidalain, PO, Amara, A

Cell Rep 2017
33462580 Ivermectin Accelerates Circulating Nonstructural Protein 1 (NS1) Clearance in Adult Dengue Patients: A Combined Phase 2/3 Randomized Double-blinded Placebo Controlled Trial

Suputtamongkol, Y, Avirutnan, P, Mairiang, D, Angkasekwinai, N, Niwattayakul, K, Yamasmith, E, Saleh-Arong, FA, Songjaeng, A, Prommool, T, Tangthawornchaikul, N, Puttikhunt, C, Hunnangkul, S, Komoltri, C, Thammapalo, S, Malasit, P

Clin Infect Dis 2021
27068162 Glycosylation of dengue virus glycoproteins and their interactions with carbohydrate receptors: possible targets for antiviral therapy

Idris, F, Muharram, SH, Diah, S

Arch Virol 2016
28791003 Dengue Virus Glycosylation: What Do We Know?

Yap, SSL, Nguyen-Khuong, T, Rudd, PM, Alonso, S

Front Microbiol 2017
30102148 Human glucose-regulated protein 78 modulates intracellular production and secretion of nonstructural protein 1 of dengue virus

Songprakhon, P, Limjindaporn, T, Perng, GC, Puttikhunt, C, Thaingtamtanha, T, Dechtawewat, T, Saitornuang, S, Uthaipibull, C, Thongsima, S, Yenchitsomanus, PT, Malasit, P, Noisakran, S

J Gen Virol 2018
8176380 Glycosylation mutants of dengue virus NS1 protein

Pryor, MJ, Wright, PJ

J Gen Virol 1994
37702492 Dengue virus NS1 secretion is regulated via importin-subunit β1 controlling expression of the chaperone GRp78 and targeted by the clinical drug ivermectin

Denolly, S, Guo, H, Martens, M, Płaszczyca, A, Scaturro, P, Prasad, V, Kongmanas, K, Punyadee, N, Songjaeng, A, Mairiang, D, Pichlmair, A, Avirutnan, P, Bartenschlager, R

mBio 2023
Participants
Participates
Event Information
Catalyst Activity

dolichyl-diphosphooligosaccharide-protein glycotransferase activity of OST complex [endoplasmic reticulum membrane]

This event is regulated
Disease
Name Identifier Synonyms
dengue disease DOID:12205 breakbone fever, Dengue Fever, classic dengue
Cross References
Mondo
Authored
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