Abstract
DC-SIGN, a C-type lection expressed on dendritic cells, enhances HIV-1 infection in cis and in trans. HIV-1 circulating recombinant form (CRF) 07_BC viruses have been the predominant strain found among injection drug users in southern China and Taiwan. The goal of this study was to map the DC-SIGN-interactive domain on the gp120 of CRF07_BC. Pseudotyped viruses containing single (N233Q, N275Q, N330Q, N351Q, N355Q, N381Q, and N387Q), double (N233Q + N275Q, N233Q + N351Q, N275Q + N351Q), or triple (N233Q + N275Q + N351Q) N-glycan mutant gp120 were generated. Capture assays showed that the DC-SIGN-binding capacity of pseudoviruses with N275Q or N351Q decreased significantly. Rabbit antisera against synthetic peptides covering the N275 (R72 antiserum) or N351 (R77 antiserum) region blocked the interaction between wild-type gp120 and DC-SIGN in the capture assay. Furthermore, pseudotype viruses containing gp120 from five different CRF07_BC isolates were generated and R72 and R77 antisera blocked their interactions with DC-SIGN (80% for R72 and 40% for R77, respectively) in the capture assays. In conclusion, the N275 and N351 glycan sites on the CRF07_BC gp120 play an important role in mediating the interaction between gp120 and DC-SIGN. This information is valuable for developing both therapeutic and preventive agents for HIV-1 infection.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Blocking / immunology
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Antibodies, Blocking / pharmacology
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Binding Sites / genetics
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Binding Sites / immunology
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Cell Adhesion Molecules / immunology
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Cell Adhesion Molecules / metabolism*
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Cell Line
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China
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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HIV Envelope Protein gp120 / chemistry
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HIV Envelope Protein gp120 / genetics
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HIV Envelope Protein gp120 / immunology
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HIV Envelope Protein gp120 / metabolism*
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HIV Infections* / epidemiology
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HIV Infections* / immunology
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HIV Infections* / metabolism
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HIV Infections* / virology
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HIV-1 / genetics
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HIV-1 / immunology
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HIV-1 / isolation & purification
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HIV-1 / metabolism*
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Humans
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Immune Sera
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Immunoassay
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Lectins, C-Type / immunology
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Lectins, C-Type / metabolism*
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Models, Molecular
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Mutagenesis, Site-Directed
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Mutation
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Plasmids
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Polysaccharides / chemistry
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Polysaccharides / genetics
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Polysaccharides / immunology
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Polysaccharides / metabolism*
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Protein Binding / drug effects
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Protein Binding / genetics
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Protein Binding / immunology
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Rabbits
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Receptors, Cell Surface / immunology
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Receptors, Cell Surface / metabolism*
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Sequence Analysis, DNA
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Taiwan
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Transfection
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Virus Internalization / drug effects
Substances
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Antibodies, Blocking
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Cell Adhesion Molecules
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DC-specific ICAM-3 grabbing nonintegrin
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HIV Envelope Protein gp120
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Immune Sera
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Lectins, C-Type
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Polysaccharides
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Receptors, Cell Surface