Influence of polymorphism in dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related (DC-SIGNR) gene on HIV-1 trans-infection.
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 (R(2)=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.
Zhu
Dayong
D
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. zhu@ims.u-tokyo.ac.jp
Kawana-Tachikawa
Ai
A
Iwamoto
Aikichi
A
Kitamura
Yoshihiro
Y
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D005091:Exons; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D020080:Tandem Repeat Sequences
C433029:CLEC4M protein, human; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface