Dengue virion E protein binds CD209 on dendritic cells

Stable Identifier
R-HSA-9918501
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Dengue virus type 2
Compartment
plasma membrane
ReviewStatus
5/5
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Dengue virion E protein binds CD209 on dendritic cells
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After having infected skin keratinocytes via an unknown receptor (Duangkhae et al., 2018), Dengue virus infection of human dendritic cells (DC) involves binding of the viral envelope (E) protein to CD209 (DC-SIGN) (Tassanetrithep et al. 2003). Genetic variations in CD209 may influence susceptibility or resistance to dengue virus infection, as well as disease progression and severity (Sakuntabhai et al., 2005; reviewed in Xavier-Carvalho et al. 2017). The CD209 receptor is expressed in DCs, where it can mediate pathogen endocytosis; CD209 mRNA expression in human CD34+ progenitor-derived DCs and peripheral blood mononuclear cells (PBMCs) can be influenced by cell maturation/activation state. CD209 is also found in human placental macrophages, endothelial cells of placental vascular channels, and THP-1 monocytes (Mummidi et al., 2001; reviewed in Cruz-Oliveira et al., 2015). CD209 stays bound to the virion during endocytosis in human DC-SIGN expressing cell lines and primary human DCs (Liu et al., 2017, using DENV-1 West Pac 74 strain).

On human primary monocytes/macrophages, a CD14-dependent mechanism involving CD14-associated structures may facilitate viral entry (Chen et al., 1999), and Macrophage Mannose Receptor 1 (MRC1) mediates DENV entry (all four serotypes investigated) (Miller et al., 2008; Lo et al., 2016). On DCs and other leukocytes the CMRF35-like molecule 8 (CD300A) receptor acts as DENV coreceptor by binding phosphatidylserine and phosphatidylethanolamine on the virion (Carnec et al., 2015). Other host factors are heparan sulfate (Chen et al., 1997, shown in Vero cells) and ganglioside GM1a, which functions as a coreceptor/attachment factor for DENV1 (PVP159 strain) and DENV2 (NGC strain) in mammalian cell systems (Vero and BHK21 cells) (Tantirimudalige et al., 2022). Possible but unclear receptors are integrins like ITGAV:ITGB3 which is a known factor in West Nile Virus (WNV) infection (Schmidt et al., 2013). A role of integrins in Dengue entry has some support (reviewed in Oliveira & Peron, 2019).

Part of the assembled virions are immature, in that prM was not fully cleaved during virion assembly. These virions are only infectious if cleavage by furin happens on the cell surface or during passage through endosomes (reviewed in Rodenhuis-Zybert et al., 2011).
Literature References
PubMed ID Title Journal Year
12682107 DC-SIGN (CD209) mediates dengue virus infection of human dendritic cells

Tassaneetrithep, B, Burgess, TH, Granelli-Piperno, A, Trumpfheller, C, Finke, J, Sun, W, Eller, MA, Pattanapanyasat, K, Sarasombath, S, Birx, DL, Steinman, RM, Schlesinger, S, Marovich, MA

J Exp Med 2003
9256277 Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate

Chen, Y, Maguire, T, Hileman, RE, Fromm, JR, Esko, JD, Linhardt, RJ, Marks, RM

Nat Med 1997
21388812 Partial maturation: an immune-evasion strategy of dengue virus?

Rodenhuis-Zybert, IA, Wilschut, J, Smit, JM

Trends Microbiol 2011
18266465 The mannose receptor mediates dengue virus infection of macrophages

Miller, JL, de Wet, BJ, Martinez-Pomares, L, Radcliffe, CM, Dwek, RA, Rudd, PM, Gordon, S

PLoS Pathog 2008
29106931 Interplay between Keratinocytes and Myeloid Cells Drives Dengue Virus Spread in Human Skin

Duangkhae, P, Erdos, G, Ryman, KD, Watkins, SC, Falo, LD, Marques, ETA, Barratt-Boyes, SM

J Invest Dermatol 2018
25725010 Receptors and routes of dengue virus entry into the host cells

Cruz-Oliveira, C, Freire, JM, Conceição, TM, Higa, LM, Castanho, MA, Da Poian, AT

FEMS Microbiol Rev 2015
31063609 Viral receptors for flaviviruses: Not only gatekeepers

Oliveira, LG, Peron, JPS

J Leukoc Biol 2019
27832191 Dengue Virus Infection Is through a Cooperative Interaction between a Mannose Receptor and CLEC5A on Macrophage as a Multivalent Hetero-Complex

Lo, YL, Liou, GG, Lyu, JH, Hsiao, M, Hsu, TL, Wong, CH

PLoS One 2016
15838506 A variant in the CD209 promoter is associated with severity of dengue disease

Sakuntabhai, A, Turbpaiboon, C, Casadémont, I, Chuansumrit, A, Lowhnoo, T, Kajaste-Rudnitski, A, Kalayanarooj, SM, Tangnararatchakit, K, Tangthawornchaikul, N, Vasanawathana, S, Chaiyaratana, W, Yenchitsomanus, PT, Suriyaphol, P, Avirutnan, P, Chokephaibulkit, K, Matsuda, F, Yoksan, S, Jacob, Y, Lathrop, GM, Malasit, P, Desprès, P, Julier, C

Nat Genet 2005
10074110 Bacterial lipopolysaccharide inhibits dengue virus infection of primary human monocytes/macrophages by blockade of virus entry via a CD14-dependent mechanism

Chen, YC, Wang, SY, King, CC

J Virol 1999
26468529 The Phosphatidylserine and Phosphatidylethanolamine Receptor CD300a Binds Dengue Virus and Enhances Infection

Carnec, X, Meertens, L, Dejarnac, O, Perera-Lecoin, M, Hafirassou, ML, Kitaura, J, Ramdasi, R, Schwartz, O, Amara, A

J Virol 2016
29133029 Host genetics and dengue fever

Xavier-Carvalho, C, Cardoso, CC, de Souza Kehdy, F, Pacheco, AG, Moraes, MO

Infect Genet Evol 2017
28128492 Beyond attachment: Roles of DC-SIGN in dengue virus infection

Liu, P, Ridilla, M, Patel, P, Betts, L, Gallichotte, E, Shahidi, L, Thompson, NL, Jacobson, K

Traffic 2017
23658209 Integrins modulate the infection efficiency of West Nile virus into cells

Schmidt, K, Keller, M, Bader, BL, Korytář, T, Finke, S, Ziegler, U, Groschup, MH

J Gen Virol 2013
11337487 Extensive repertoire of membrane-bound and soluble dendritic cell-specific ICAM-3-grabbing nonintegrin 1 (DC-SIGN1) and DC-SIGN2 isoforms. Inter-individual variation in expression of DC-SIGN transcripts

Mummidi, S, Catano, G, Lam, L, Hoefle, A, Telles, V, Begum, K, Jimenez, F, Ahuja, SS, Ahuja, SK

J Biol Chem 2001
36209827 The ganglioside GM1a functions as a coreceptor/attachment factor for dengue virus during infection

Tantirimudalige, SN, Raghuvamsi, PV, Sharma, KK, Wei Bao, JC, Anand, GS, Wohland, T

J Biol Chem 2022
Participants
Input
Output
Participates
as an event of
This event is regulated
Positively by
Regulator
HSPGs [plasma membrane] (Homo sapiens)
Regulator
MRC1 [plasma membrane] (Homo sapiens)
Regulator
CD14 [plasma membrane] (Homo sapiens)
Regulator
CD300A [plasma membrane] (Homo sapiens)
Regulator
GM1a [plasma membrane]
Disease
Name Identifier Synonyms
dengue disease DOID:12205 breakbone fever, Dengue Fever, classic dengue
Cross References
Mondo
Authored
Orlic-Milacic, M  (2024-08-15)
Reviewed
Mansur, DS  (2025-10-29)
Roque Ascenção, F  (2025-10-29)
Created
Orlic-Milacic, M  (2024-08-15)
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