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Journal of Virology, January 2002, p. 32-40, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.32-40.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Binding of LFA-1 (CD11a) to Intercellular Adhesion Molecule 3 (ICAM-3; CD50) and ICAM-2 (CD102) Triggers Transmigration of Human Immunodeficiency Virus Type 1-Infected Monocytes through Mucosal Epithelial Cells

Marie-Paule Carreno,^1* Nicolas Chomont,¹ Michel D. Kazatchkine,^1,2 Theano Irinopoulou,² Corrine Krief,¹ Ali-Si Mohamed,² Laurent Andreoletti,² Mathieu Matta,² and Laurent Belec^1,2

Unité 430, Hôpital Broussais, Institut National de la Santé et de la Recherche Médicale,¹ Université Pierre et Marie Curie (Paris VI), Paris, France²

Received 25 May 2001/ Accepted 19 September 2001

Transmigration of human immunodeficiency virus (HIV)-infected mononuclear cells through the genital mucosa is one of the possible mechanisms of sexual transmission of HIV. Here, we investigated the transmigration of cell-associated R5-tropic HIV type 1 (HIV-1) through a tight monolayer of human epithelial cells in vitro. We show that this process is dependent on an initial interaction between Lß2 integrin CD11a/CD18 on infected monocytic cells and intercellular adhesion molecule 2 (ICAM-2; CD102) and ICAM-3 (CD50) on the apical membrane of epithelial cells. The CD50 and CD102 ligands were overexpressed on epithelial cells when the cells were activated by proinflammatory cytokines in the cellular microenvironment. An accumulation of proviral DNA was found in the transmigrated cells, clearly reflecting the preferential transepithelial migration of HIV-1-infected cells under proinflammatory conditions. Our observations provide new insights supporting the hypothesis that HIV-infected mononuclear cells contained in genital secretions from infected individuals may cross the epithelial genital mucosa of an exposed receptive sexual partner, particularly under inflammatory conditions of damaged genital tissue. Understanding the fundamental aspects of the initial HIV entry process during sexual transmission remains a critical step for preventing human infection and developing further vaccinal strategies and virucidal agents.

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* Corresponding author. Mailing address: INSERM U430, 96, rue Didot, 75674 Paris Cedex 14, France. Phone: 33 1 43 95 95 67. Fax: 33 1 45 45 90 59. E-mail: marie-paule.carreno{at}brs.ap-hop-paris.fr.

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Journal of Virology, January 2002, p. 32-40, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.32-40.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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