DC-SIGN plays a stronger role than DCIR in mediating HIV-1 capture and transfer

Wei Jin; Chang Li; Tao Du; Kai Hu; Xin Huang; Qinxue Hu

doi:10.1016/j.virol.2014.04.016

DC-SIGN plays a stronger role than DCIR in mediating HIV-1 capture and transfer

Virology. 2014 Jun:458-459:83-92. doi: 10.1016/j.virol.2014.04.016. Epub 2014 May 8.

Authors

Wei Jin¹, Chang Li¹, Tao Du², Kai Hu², Xin Huang¹, Qinxue Hu³

Affiliations

¹ State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, 44 Xiaohongshan Zhongqu, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, 44 Xiaohongshan Zhongqu, Wuhan 430071, China.
³ State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, 44 Xiaohongshan Zhongqu, Wuhan 430071, China; Center for Infection and Immunity, St George׳s University of London, London SW17 0RE, UK. Electronic address: qhu@wh.iov.cn.

PMID: 24928041
DOI: 10.1016/j.virol.2014.04.016

Abstract

The C-type lectin receptors (CLRs) expressed on dendritic cells (DCs), in particular DC-SIGN and DCIR, likely play an important role in HIV-1 early infection. Here, we systematically compared the capture and transfer capability of DC-SIGN and DCIR using a wide range of HIV-1 isolates. Our results indicated that DC-SIGN plays a stronger role than DCIR in DC-mediated HIV-1 capture and transfer. This was further strengthened by the data from transient and stable transfectants, showing that DC-SIGN had better capability, compared with DCIR in HIV-1 capture and transfer. Following constructing and analyzing a series of soluble DC-SIGN and DCIR truncates and chimeras, we demonstrated that the neck domain, but not the CRD, renders DC-SIGN higher binding affinity to gp120 likely via the formation of tetramerization. Our findings provide insights into CLR-mediated HIV-1 capture and transfer, highlighting potential targets for intervention strategies against gp120-CLR interactions.

Keywords: C-type lectin receptor; Capture; DC-SIGN; DCIR; HIV-1; Transfer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Binding Sites
Cell Adhesion Molecules / genetics
Cell Adhesion Molecules / metabolism*
Cells, Cultured
Dendritic Cells
Gene Expression Regulation
Gene Knockdown Techniques
Genetic Engineering
HIV Envelope Protein gp120 / genetics
HIV Envelope Protein gp120 / metabolism
HIV-1 / metabolism*
Humans
Lectins, C-Type / genetics
Lectins, C-Type / metabolism*
Membrane Glycoproteins / genetics
Membrane Glycoproteins / metabolism*
Receptors, Cell Surface / genetics
Receptors, Cell Surface / metabolism*
Receptors, Immunologic / genetics
Receptors, Immunologic / metabolism*

Substances

CLEC4A protein, human
Cell Adhesion Molecules
DC-specific ICAM-3 grabbing nonintegrin
HIV Envelope Protein gp120
Lectins, C-Type
Membrane Glycoproteins
Receptors, Cell Surface
Receptors, Immunologic
gp120 protein, Human immunodeficiency virus 1