CLEC4A binds HIV and HCV glycoproteins

Stable Identifier
Reaction [binding]
Homo sapiens
Related Species
Human immunodeficiency virus 1, Hepatitis C virus genotype 2a
Locations in the PathwayBrowser
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CLEC4A (C-type lectin domain family 4 member A/Dendritic cell immunoreceptor (DCIR)) is expressed by all CD14+ monocytes, CD15+ granulocytes, all dendrite cell (DC) subsets and B cells in peripheral blood. The extracellular domain of CLEC4A has an EPS motif which recognises carbohydrates but the definitive carbohydrate ligands have not been defined. However, it has been identified as an attachment factor for HIV on DCs and hepatitis C virus (HCV) glycoprotein E2 on plasmacytoid dendritic cells (pDCs) (Lambert et al. 2008, Florentin et al. 2012, Kerscher et al. 2013).
Unlike the other Dectin-2 family members, CLEC4A has a long cytoplasmic tail with a classical immunoreceptor tyrosine based inhibitory signalling motif (ITIMs) (Flornes et al. 2004). CLEC4A with its ITIM motif mediates inhibitory signalling through activation of the phosphatases SHP1 and SHP2 (Kanazawa et al 2003, Meyer-Wentrup et al. 2009). Activation of CLEC4A on DCs or pDCs leads to inhibition of TLR8-mediated IL12 and TNF production, and TLR9-induced IFN-alpha production (Lambert et al. 2011, Meyer-Wentrup et al. 2008).
In humans, polymorphisms of CLEC4A have been associated with susceptibility to rheumatoid arthritis (Lorentzen et al. 2007).

Literature References
PubMed ID Title Journal Year
23053572 HCV glycoprotein E2 is a novel BDCA-2 ligand and acts as an inhibitor of IFN production by plasmacytoid dendritic cells

Baumert, TF, Soumelis, V, Hirsch, I, Stranska, R, Dental, C, Olive, D, Firaguay, G, Florentin, J, Gondois-Rey, F, Nun├Ęs, JA, Thumann, C, Aouar, B

Blood 2012
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