CD209 gene

The CD209 gene(CD209 stands for Cluster of Differentiation 209) is a protein-coding gene located on chromosome 19p13.2. This gene encodes a C-type lectin that plays a role in cell adhesion and the recognition of pathogens. This receptor recognizes a broad spectrum of evolutionarily different pathogens, including leprosy and tuberculosis mycobacteria, the Ebola, hepatitis C, HIV-1 and dengue viruses as well as the acute respiratory syndrome coronavirus SARS-CoV. An important paralog of this gene is CLEC4M.

The CD209 protein is divided into four distinct domains: a C-terminal carbohydrate recognition domain, a flexible tandem repeat neck domain, a transmembrane region and an N-terminal cytoplasmic domain involved in internalization. The CD209 gene is closely related in both sequence and function to a neighboring gene, CLEC4M (Gene ID: 10332), also known as L-SIGN. The two genes differ in viral recognition and expression patterns, with this gene showing high expression on the surface of dendritic cells. Versch. Polymorphisms of the gene are associated with protection against HIV-1 infections, while single nucleotide polymorphisms in the promoter of this gene are associated with different resistance and susceptibility to and severity of infectious diseases (e.g. severe SARS infections).

Diseases associated with CD209 include dengue virus and human immunodeficiency virus type 1.

The encoded protein is a pathogen recognition receptor that is expressed on the surface of immature dendritic cells (DCs) and is involved in triggering the primary immune response. It is thought to mediate the endocytosis of pathogens, which are subsequently degraded in lysosomal compartments. The receptor returns to the cell membrane surface and the pathogen-derived antigens are presented to resting T cells via MHC class II proteins to initiate the adaptive immune response.

On dendritic cells (DCs), the CD209 protein is a receptor with high affinity for ICAM2(CD102)and ICAM3(CD50) by binding to mannose-like carbohydrates. May act as a DC rolling receptor that mediates transendothelial migration of DC precursors from blood to tissue by binding endothelial ICAM2. The CD209 protein appears to regulate DC-induced T cell proliferation by binding to ICAM3 on T cells in the immunological synapse formed between DC and T cells.

The CD209 protein:

• Acts as a binding receptor for HIV-1 and HIV-2.
• Acts as a binding receptor for Ebola virus.
• Acts as an attachment receptor for cytomegalovirus.
• Acts as a binding receptor for HCV.
• Acts as an attachment receptor for dengue virus.
• Acts as a binding receptor for measles virus.
• Acts as an attachment receptor for herpes simplex virus 1.
• Acts as a binding receptor for influenza virus A.
• Acts as a binding receptor for SARS-CoV.
• Acts as a binding receptor for Japanese encephalitis virus.
• Acts as an attachment receptor for Lassa virus (PubMed:23966408).
• Acts as an attachment receptor for Marburg virus.
• Acts as an attachment receptor for respiratory syncytial virus.
• Acts as an attachment receptor for Rift Valley fever virus and Uukuniemi virus.
• Acts as a binding receptor for West Nile virus.
• Likely recognizes N-linked high mannose oligosaccharides in a calcium-dependent manner in a variety of bacterial pathogen antigens, including Leishmania pifanoi LPG, Lewis-x antigen in Helicobacter pylori LPS, mannose in Klebsiella pneumonae LPS, di-mannose and tri-mannose in Mycobacterium tuberculosis ManLAM, and Lewis-x antigen in Schistosoma mansoni SEA (Barreiro LB et al. 2006). Recognition of M. tuberculosis by dendritic cells also occurs in part via this molecule (Carroll MV et al. 2010).

1. Barreiro LB et al. (2006) Promoter variation in the DC-SIGN-encoding gene CD209 is associated with tuberculosis. PLoS Med 3:e20
2. Carroll MV et al. (2010) Identification of four novel DC-SIGN ligands on Mycobacterium bovis BCG. Protein Cell 1:859-870)
3. Davis CW et al. (2006) West Nile virus discriminates between DC-SIGN and DC-SIGNR for cellular attachment and infection. J Virol 80:1290-301
4. Halary F et al. (2002) Human cytomegalovirus binding to DC-SIGN is required for dendritic cell infection and target cell trans-infection. Immunity 17:653-664.