Host cell surface receptors for Ebola virus glycoprotein

The host cell surface receptors for the Ebola virus glycoprotein (GP) are a diverse group of proteins that facilitate the initial attachment and internalization of the virus into host cells. Unlike many viruses that use a single specific cell surface receptor, Ebola virus (EBOV) utilizes multiple attachment factors, including T-cell immunoglobulin and mucin domain 1 (TIM-1), Tyro3/Axl/Mer (TAM) family receptors (particularly Axl), and various C-type lectins such as DC-SIGN and L-SIGN (Alvarez et al., 2002; Shimojima et al., 2007; Kondratowicz et al., 2011). These receptors interact with either the glycans on the viral GP or phosphatidylserine (PS) on the viral envelope, triggering macropinocytosis or other endocytic pathways to bring the virion into the cell (Hunt et al., 2011; Nanbo et al., 2010). Once internalized, the virus is trafficked to late endosomes where the GP is proteolytically processed by cathepsins to expose the binding site for the essential intracellular receptor, Niemann-Pick C1 (NPC1), which mediates membrane fusion and viral genome release (Carette et al., 2011; Cote et al., 2011). Targeting these cell surface receptors or the subsequent endosomal entry steps represents a significant therapeutic strategy to prevent viral infection and spread, with several small molecules and antibodies currently under investigation (Yuan et al., 2015; Stewart et al., 2019).

Other names

Ebola virus attachment factorsEBOV entry receptorsT-cell immunoglobulin and mucin domain 1 (TIM-1)Axl receptor tyrosine kinaseDC-SIGN (CD209)L-SIGN (CLEC4M)hMGL (CLEC10A)LSECtin (CLEC4G)Beta-1 integrin (ITGB1)Folate receptor alpha (FR-alpha)

Inhibition of viral attachment to cell surface factors, blocking of macropinocytosis-mediated internalization, and prevention of endosomal glycoprotein-receptor interactions.