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.
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.
Marzi
Andrea
A
Institute of Virology, Nikolaus-Fiebiger-Center for Molecular Medicine, Erlangen, Germany.
Möller
Peggy
P
Hanna
Sheri L
SL
Harrer
Thomas
T
Eisemann
Jutta
J
Steinkasserer
Alexander
A
Becker
Stephan
S
Baribaud
Frédéric
F
Pöhlmann
Stefan
S
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D029043:Ebolavirus / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology; D014764:Viral Proteins / Q000502:physiology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D014764:Viral Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human