Journal article
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)
The Journal of biological chemistry, Vol.285(3), pp.2100-2112
01/15/2010
DOI: 10.1074/jbc.M109.030619
PMCID: PMC2804366
PMID: 19833723
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.
Details
- Title: Subtitle
- 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)
- Creators
- Nancy P. Y Chung - HIV Drug Resistance Program, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702Sabine K. J Breun - Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, D-04103 Leipzig, GermanyArman Bashirova - Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702, andJoerg G Baumann - Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, D-04103 Leipzig, GermanyThomas D Martin - HIV Drug Resistance Program, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702Jaideep M Karamchandani - HIV Drug Resistance Program, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702Jason W Rausch - HIV Drug Resistance Program, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702Stuart F. J Le Grice - HIV Drug Resistance Program, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702Li Wu - Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226Mary Carrington - Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702, andVineet N KewalRamani - HIV Drug Resistance Program, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.285(3), pp.2100-2112
- DOI
- 10.1074/jbc.M109.030619
- PMID
- 19833723
- PMCID
- PMC2804366
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
- Grant note
- HHSN261200800001E / National Institutes of Health
- Language
- English
- Date published
- 01/15/2010
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984002377902771
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