Marzi A, Möller P, Hanna SL, Harrer T, Eisemann J, Steinkasserer A, Becker S, Baribaud F, Pöhlmann S (2007): Analysis of the interaction of Ebola virus glycoprotein with DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin) and its homologue DC-SIGNR
J. Infect. Dis. 196 (Suppl. 2): S237-246.

Background. The lectin DC‐SIGN (dendritic cell–specific intercellular adhesion molecule 3–grabbing nonintegrin) augments Ebola virus (EBOV) infection. However, it its unclear whether DC‐SIGN promotes only EBOV attachment (attachment factor function, nonessential) or actively facilitates EBOV entry (receptor function, essential).

Methods. We investigated whether DC‐SIGN on B cell lines and dendritic cells acts as an EBOV attachment factor or receptor.

Results. Engineered DC‐SIGN expression rendered some B cell lines susceptible to EBOV glycoprotein (EBOV GP)–driven infection, whereas others remained refractory, suggesting that cellular factors other than DC‐SIGN are also required for susceptibility to EBOV infection. Augmentation of entry was independent of efficient DC‐SIGN internalization and might not involve lectin‐mediated endocytic uptake of virions. Therefore, DC‐SIGN is unlikely to function as an EBOV receptor on B cell lines; instead, it might concentrate virions onto cells, thereby allowing entry into cell lines expressing low levels of endogenous receptor(s). Indeed, artificial concentration of virions onto cells mirrored DC‐SIGN expression, confirming that optimization of viral attachment is sufficient for EBOV GP–driven entry into some B cell lines. Finally, EBOV infection of dendritic cells was only partially dependent on mannose‐specific lectins, such as DC‐SIGN, suggesting an important contribution of other factors.

Conclusions. Our results indicate that DC‐SIGN is not an EBOV receptor but, rather, is an attachment‐promoting factor that boosts entry into B cell lines susceptible to low levels of EBOV GP–mediated infection.