Influence of polymorphism in dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related (DC-SIGNR) gene on HIV-1 trans-infection |
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Authors: | Dayong Zhu Yoshihiro Kitamura |
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Affiliation: | a Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan b Research Center for Asian Infectious Diseases, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan c China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Olympic Park of Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Bejing 100101, China |
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Abstract: | The dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and DC-SIGN-related (DC-SIGNR) molecules on the cell surface are known to enhance human immunodeficiency virus type 1 (HIV-1) infection by capturing the virions and transmitting them to CD4+ T-cell, a process termed trans-infection. The neck region and carbohydrate recognition domain of the two proteins are important for efficient binding to the HIV-1 envelope protein. DC-SIGNR is polymorphic in Exons 4 and 5 that encode the neck region and carbohydrate recognition domain, respectively; the former contains a variable number of tandem repeats, and the latter the SNP (rs2277998). Since it remains unclear whether the DC-SIGNR polymorphism is related to the risk of HIV-1 infection, we tested possible effects of the polymorphism on HIV-1 trans-infection efficiency, by constructing six kinds of cDNAs encoding DC-SIGNR variants with various numbers of repeat units and various SNP. We were able to express the variants on the surface of Raji cells, a human B cell line. Flow cytometry showed that all the tested DC-SIGNR molecules were efficiently expressed on the cell surface at various levels; the assay for HIV trans-infection efficacy showed that all the tested variants had that activity with different efficacy levels. We found a correlation between the HIV trans-infection efficiency and the mean fluorescent intensity of DC-SIGNR expression (R2 = 0.95). Thus, our results suggest that the variation of the tested DC-SIGNR genotypes affects the efficacy of trans-infection by affecting the amounts of the protein expressed on the cell surface. |
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Keywords: | Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related Polymorphism Trans-infection Human immunodeficiency virus |
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