Evidence that multiple defects in murine DC-SIGN inhibit a functional interaction with pathogens.
Certain viruses, bacteria, fungi and parasites target dendritic cells through the interaction with the cellular attachment factor DC-SIGN, making this C-type lectin an attractive target for therapeutic intervention. Studies on DC-SIGN function would be greatly aided by the establishment of a mouse model, however, it is unclear if the murine (m) homologue of human (h) DC-SIGN also binds to pathogens. Here, we investigated the interaction of mDC-SIGN, also termed CIRE, with the Ebolavirus glycoprotein (EBOV-GP), a ligand of hDC-SIGN. We found that mDC-SIGN neither binds EBOV-GP nor enhances infection by reporterviruses pseudotyped with EBOV-GP. Analysis of chimeras between mDC-SIGN and hDC-SIGN provided evidence that determinants in the carbohydrate recognition domain and in the neck domain of mDC-SIGN inhibit a functional interaction with EBOV-GP. Moreover, mDC-SIGN was found be monomeric, suggesting that lack of multimerization, which is believed to be required for efficient pathogen recognition by hDC-SIGN, might be one factor that prevents binding of mDC-SIGN to EBOV-GP. Our results suggest that mDC-SIGN on murine dendritic cells is not an adequate model for pathogen interactions with hDC-SIGN.
Gramberg
Thomas
T
Institute for Clinical and Molecular Virology, University Erlangen-Nürnberg, 91054 Erlangen, Germany.
Caminschi
Irina
I
Wegele
Anja
A
Hofmann
Heike
H
Pöhlmann
Stefan
S
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D019281:Dimerization; D029043:Ebolavirus / Q000378:metabolism* / Q000472:pathogenicity*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013045:Species Specificity; D014764:Viral Proteins / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin