Low-density lipoprotein receptor class A domain-containing 3 (LDLRAD3)

LDLRAD3 is a cell surface receptor belonging to the low-density lipoprotein receptor (LDLR) family and has been identified as the primary host cell receptor required for optimal attachment and entry of Venezuelan equine encephalitis virus (VEEV). VEEV utilizes this receptor to gain entry via receptor-mediated endocytosis, a critical step in its infection and subsequent pathogenesis in both murine (mouse) models and cell culture[5][6]. The interaction involves VEEV envelope glycoproteins E2 and E1 binding directly to regions within LDLRAD3, and loss-of-function mutations in contact residues of LDLRAD3 can abolish viral infectivity, confirming its essential role[5][6]. While other cell surface molecules, such as heparan sulfate, may mediate attachment in tissue culture-adapted strains, LDLRAD3 is the major, biologically relevant entry receptor in vivo[5][3]. Currently, no approved therapeutic drugs directly target LDLRAD3 or utilize it for patient selection or disease monitoring. Its safety profile as a therapeutic target is not fully elucidated, but as a host protein, interventions could risk broader effects on host physiology or cellular cholesterol/metabolism processes.

Other names

LDL receptor class A domain-containing protein 3LDLRAD3putative VEEV receptor

Acts as the cell surface attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV), mediating virus entry into host cells through receptor-mediated endocytosis