Host cell surface receptors involved in Dengue virus entry (DENV entry receptors)

Dengue virus (DENV) entry into host cells is a complex, multi-step process involving several cell surface molecules that act as attachment factors or entry receptors. Initial tethering is frequently mediated by heparan sulfate proteoglycans (HSPGs) and C-type lectins, most notably DC-SIGN (CD209) on dendritic cells and L-SIGN (CD209L) on endothelial cells, which bind to the N-linked glycans of the DENV envelope (E) protein [PMID: 12502850, 25157315]. Subsequent to attachment, the virus utilizes receptors such as AXL, a member of the TAM family of receptor tyrosine kinases, and TIM-1 to facilitate internalization through a process known as apoptotic mimicry [PMID: 23472551]. Other proteins, including the chaperone GRP78 and the signaling receptor CLEC5A, are also involved in the entry or the induction of the pro-inflammatory response following infection [PMID: 18496526]. Because DENV can infect a wide range of cell types using different combinations of these receptors, they are considered significant therapeutic targets for the development of entry inhibitors. However, the redundancy of these entry pathways and the physiological importance of the host proteins present challenges for achieving high efficacy without significant toxicity.

Other names

Dengue virus entry receptorsDENV attachment factorsCD209 (DC-SIGN)CD209L (L-SIGN)AXL receptor tyrosine kinaseCLEC5ATIM-1 (HAVCR1)GRP78 (HSPA5)Heparan sulfate proteoglycans (HSPG)Mannose receptor (CD206)

Inhibition of viral attachment to host cells, blockade of receptor-mediated endocytosis, and interference with phosphatidylserine-mediated apoptotic mimicry to prevent viral internalization.