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Journal of Virology, May 2001, p. 4780-4791, Vol. 75, No. 10
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.10.4780-4791.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Cell-to-Cell Contact Results in a Selective Translocation of Maternal Human Immunodeficiency Virus Type 1 Quasispecies across a Trophoblastic Barrier by both Transcytosis and Infection

S. Lagaye,1,* M. Derrien,1,2 E. Menu,1,3 C. Coïto,2 E. Tresoldi,4 P. Mauclère,5 G. Scarlatti,4 G. Chaouat,3 F. Barré-Sinoussi,1 M. Bomsel,2 and the European Network for the Study of In Utero Transmission of HIV-1dagger

Institut Pasteur, Unité de Biologie des Rétrovirus, 75 724 Paris Cedex 15,1 INSERM U 131, Hôpital Antoine Béclère, 92 140 Clamart,3 and INSERM U 332, Institut Cochin de Génétique Moléculaire, 75014 Paris,2 France; Unit of Immunology, DIBIT, San Raffaele Scientific Institute, 20 132 Milan, Italy4; and Centre Pasteur du Cameroun, Yaoundé, Cameroon5

Received 23 October 2000/Accepted 22 February 2001

Mother-to-child transmission can occur in utero, mainly intrapartum and postpartum in case of breastfeeding. In utero transmission is highly restricted and results in selection of viral variant from the mother to the child. We have developed an in vitro system that mimics the interaction between viruses, infected cells present in maternal blood, and the trophoblast, the first barrier protecting the fetus. Trophoblastic BeWo cells were grown as a tight polarized monolayer in a two-chamber system. Cell-free virions applied to the apical pole neither crossed the barrier nor productively infected BeWo cells. In contrast, apical contact with human immunodeficiency virus (HIV)-infected peripheral blood mononuclear cells (PBMCs) resulted in transcytosis of infectious virus across the trophoblastic monolayer and in productive infection correlating with the fusion of HIV-infected PBMCs with trophoblasts. We showed that viral variants are selected during these two steps and that in one case of in utero transmission, the predominant maternal viral variant characterized after transcytosis was phylogenetically indistinguishable from the predominant child's virus. Hence, the first steps of transmission of HIV-1 in utero appear to involve the interaction between HIV type 1-infected cells and the trophoblastic layer, resulting in the passage of infectious HIV by transcytosis and by fusion/infection, both leading to a selection of virus quasispecies.

* Corresponding author. Present address: INSERM U342, Hôpital saint Vincent de Paul, 82, Avenue Denfert-Rochereau, 75014 Paris, France. Phone: 33-1-40-48-82-49. Fax: 33-1-40-48-83-52. E-mail: lagaye{at}icgm.cochin.inserm.fr.

dagger Participants of the European Network for In Utero Transmission of HIV-1 who contributed to this study include the following: B. Mognetti and M. Moussa (INSERM U 131, Clamart, France); P. Martin, A. Ayouba, and E. Tina (Centre Pasteur, Yaoundé, Cameroon); E. M. Fenyö and C. Tscherning (Karolinska Institute---Microbiology and Tumorbiology Center, Stockholm, Sweden); D. Dormont, P. Roques, and C. Depienne (CEA/CENFAR, Fontenay aux Roses, France); P. Gounon and A. Topilko (Institut Pasteur, Paris, France); and I. Athanassakis (Department of Biology, Division of Immunology, University of Crete, Heraklion, Greece).

Journal of Virology, May 2001, p. 4780-4791, Vol. 75, No. 10
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.10.4780-4791.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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