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Journal of Virology, November 2005, p. 13519-13527, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13519-13527.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Sugar-Binding Proteins Potently Inhibit Dendritic Cell Human Immunodeficiency Virus Type 1 (HIV-1) Infection and Dendritic-Cell-Directed HIV-1 Transfer

Stuart G. Turville,{dagger} Kurt Vermeire, Jan Balzarini, and Dominique Schols*

Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium

Received 28 January 2005/ Accepted 9 August 2005

Both endocytic uptake and viral fusion can lead to human immunodeficiency virus type 1 (HIV-1) transfer to CD4+ lymphocytes, either through directional regurgitation (infectious transfer in trans [I-IT]) or through de novo viral production in dendritic cells (DCs) resulting in a second-phase transfer to CD4+ lymphocytes (infectious second-phase transfer [I-SPT]). We have evaluated in immature monocyte-derived DCs both pathways of transfer with regard to their susceptibilities to being blocked by potential microbicidal compounds, including cyanovirin (CNV); the plant lectins Hippeastrum hybrid agglutinin, Galanthus nivalis agglutinin, Urtica dioica agglutinin, and Cymbidium hybrid agglutinin; and the glycan mannan. I-IT was a relatively inefficient means of viral transfer compared to I-SPT at both high and low levels of the viral inoculum. CNV was able to completely block I-IT at 15 µg/ml. All other compounds except mannan could inhibit I-IT by at least 90% when used at doses of 15 µg/ml. In contrast, efficient inhibition of I-SPT was remarkably harder to achieve, as 50% effective concentration levels for plant lectins and CNV to suppress this mode of HIV-1 transfer increased significantly. Thus, our findings indicate that I-SPT may be more elusive to targeting by antiviral drugs and stress the need for drugs affecting the pronounced inhibition of the infection of DCs by HIV-1.


* Corresponding author. Mailing address: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Phone: 32-16-337373. Fax: 32-16-337340. E-mail: Dominique.schols{at}rega.kuleuven.be.

{dagger} Present address: Center for Biomedical Research, Population Council, New York, NY 10021.


Journal of Virology, November 2005, p. 13519-13527, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13519-13527.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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