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Journal of Virology, December 2001, p. 12028-12038, Vol. 75, No. 24
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.24.12028-12038.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

cis Expression of DC-SIGN Allows for More Efficient Entry of Human and Simian Immunodeficiency Viruses via CD4 and a Coreceptor

Benhur Lee,1,2,* George Leslie,3 Elizabeth Soilleux,4 Una O'Doherty,3 Sarah Baik,1 Ernest Levroney,1 Karen Flummerfelt,1 William Swiggard,3 Nicholas Coleman,4 Michael Malim,3 and Robert W. Doms3,*

Department of Microbiology, Immunology & Molecular Genetics, UCLA School of Medicine1 and UCLA AIDS Institute,2 Los Angeles, California 90095; Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 191043; and Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Center, Cambridge CB2 2XZ, United Kingdom4

Received 24 July 2001/Accepted 18 September 2001

DC-SIGN is a C-type lectin expressed on dendritic cells and restricted macrophage populations in vivo that binds gp120 and acts in trans to enable efficient infection of T cells by human immunodeficiency virus type 1 (HIV-1). We report here that DC-SIGN, when expressed in cis with CD4 and coreceptors, allowed more efficient infection by both HIV and simian immunodeficiency virus (SIV) strains, although the extent varied from 2- to 40-fold, depending on the virus strain. Expression of DC-SIGN on target cells did not alleviate the requirement for CD4 or coreceptor for viral entry. Stable expression of DC-SIGN on multiple lymphoid lines enabled more efficient entry and replication of R5X4 and X4 viruses. Thus, 10- and 100-fold less 89.6 (R5/X4) and NL4-3 (X4), respectively, were required to achieve productive replication in DC-SIGN-transduced Jurkat cells when compared to the parental cell line. In addition, DC-SIGN expression on T-cell lines that express very low levels of CCR5 enabled entry and replication of R5 viruses in a CCR5-dependent manner, a property not exhibited by the parental cell lines. Therefore, DC-SIGN expression can boost virus infection in cis and can expand viral tropism without affecting coreceptor preference. In addition, coexpression of DC-SIGN enabled some viruses to use alternate coreceptors like STRL33 to infect cells, whereas in its absence, infection was not observed. Immunohistochemical and confocal microscopy data indicated that DC-SIGN was coexpressed and colocalized with CD4 and CCR5 on alveolar macrophages, underscoring the physiological significance of these cis enhancement effects.


* Corresponding author. Mailing address for Benhur Lee: Department of Microbiology, Immunology & Molecular Genetics, UCLA, 3825 Molecular Sciences Building, 609 Charles E. Young Dr. East, Los Angeles, CA 90095-1489. Phone: (310) 794-2132. Fax: (310) 267-2580. E-mail: benhurL{at}microbio.ucla.edu. Mailing address for Robert W. Doms: Department of Microbiology, University of Pennsylvania, 225 Johnson Pavilion, 36th and Hamilton Walk, Philadelphia, PA 19104. Phone: (215) 898-0890. Fax: (215) 898-9557. E-mail: doms{at}mail.med.upenn.edu.


Journal of Virology, December 2001, p. 12028-12038, Vol. 75, No. 24
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.24.12028-12038.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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