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HIV-1 transmission by dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is regulated by determinants in the carbohydrate recognition domain that are absent in liver/lymph node-SIGN (L-SIGN)

 
: Chung, Nancy P.Y.; Breun, Sabine; Bashirova, Arman; Baumann, Jörg; Martin, Thomas D.; Karamchandani, Jaideep M.; Rausch, Jason; Grice, Stuart le; Wu, Li; Carrington, Mary; Kewalramani, Vineet

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The Journal of biological chemistry 285 (2010), No.3, pp.2100-2112
ISSN: 0021-9258
ISSN: 1083-351X
English
Journal Article
Fraunhofer IZI ()
Humanes Immundefizienzvirus; C-Typ Lektine; DC-SIGN; L-SIGN; carbohydrate recognition domain (CRD)

Abstract
In this study, we identify determinants in dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) necessary for human immunodeficiency virus, type 1 (HIV-1), transmission. Although human B cell lines expressing DC-SIGN efficiently capture and transmit HIV-1 to susceptible target cells, cells expressing the related molecule liver/lymph node-specific ICAM-3-grabbing nonintegrin (L-SIGN) do not. To understand the differences between DC-SIGN and L-SIGN that affect HIV-1 interactions, we developed Raji B cell lines expressing different DC-SIGN/L-SIGN chimeras. Testing of the chimeras demonstrated that replacement of the DC-SIGN carbohydrate-recognition domain (CRD) with that of L-SIGN was sufficient to impair virus binding and prevent transmission. Conversely, the ability to bind and transmit HIV-1 was conferred to L-SIGN chimeras containing the DC-SIGN CRD. We identified Trp-258 in the DC-SIGN CRD to be essential for HIV-1 transmission. Although introduction of a K270W mutation at the same position in L-SIGN was insufficient for HIV-1 binding, an L-SIGN mutant molecule with K270W and a C-terminal DC-SIGN CRD subdomain transmitted HIV-1. These data suggest that DC-SIGN structural elements distinct from the oligosaccharide-binding site are required for HIV-1 glycoprotein selectivity.

: http://publica.fraunhofer.de/documents/N-139738.html