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J Infect Dis. 2007 Nov 15;196:S237-46. doi: 10.1086/520607.

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.

The Journal of infectious diseases

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

Affiliations

  1. Institute of Virology, Nikolaus-Fiebiger-Center for Molecular Medicine, Erlangen, Germany.

PMID: 17940955 PMCID: PMC7110133 DOI: 10.1086/520607

Abstract

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.

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