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

Marzi, Andrea; Möller, Peggy; Hanna, Sheri L.; Harrer, Thomas; Eisemann, Jutta; Steinkasserer, Alexander; Becker, Stephan; Baribaud, Frédéric; Pöhlmann, Stefan

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 DCSIGN 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 attachmentpromoting factor that boosts entry into B cell lines susceptible to low levels of EBOV GP-mediated infection.