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Journal of Virology, August 2002, p. 7812-7821, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7812-7821.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Differential Transmission of Human Immunodeficiency Virus Type 1 by Distinct Subsets of Effector Dendritic Cells

Rogier W. Sanders,1 Esther C. de Jong,2,3 Christopher E. Baldwin,1 Joost H. N. Schuitemaker,2 Martien L. Kapsenberg,2,3 and Ben Berkhout1*

Department of Human Retrovirology,,1 Department of Cell Biology and Histology,2 Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands3

Received 14 November 2001/ Accepted 4 May 2002

Dendritic cells (DC) support human immunodeficiency virus type 1 (HIV-1) transmission by capture of the virus particle in the mucosa and subsequent transport to the draining lymph node, where HIV-1 is presented to CD4+ Th cells. Virus transmission involves a high-affinity interaction between the DC-specific surface molecule DC-SIGN and the viral envelope glycoprotein gp120 and subsequent internalization of the virus, which remains infectious. The mechanism of viral transmission from DC to T cells is currently unknown. Sentinel immature DC (iDC) develop into Th1-promoting effector DC1 or Th2-promoting DC2, depending on the activation signals. We studied the ability of these effector DC subsets to support HIV-1 transmission in vitro. Compared with iDC, virus transmission is greatly upregulated for the DC1 subset, whereas DC2 cells are inactive. Increased transmission by DC1 correlates with increased expression of ICAM-1, and blocking studies confirm that ICAM-1 expression on DC is important for HIV transmission. The ICAM-1-LFA-1 interaction is known to be important for immunological cross talk between DC and T cells, and our results indicate that this cell-cell contact is exploited by HIV-1 for efficient transmission.

* Corresponding author. Mailing address: Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. Phone: 31 20 5664822. Fax: 31 20 5669064. E-mail: b.berkhout{at}amc.uva.nl.

Journal of Virology, August 2002, p. 7812-7821, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7812-7821.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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