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Journal of Virology, January 2007, p. 395-405, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01303-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Cell-Free Human Immunodeficiency Virus Type 1 Transcytosis through Primary Genital Epithelial Cells{triangledown}

Michael D. Bobardt,1 Udayan Chatterji,1 Suganya Selvarajah,1 Bernadette Van der Schueren,2 Guido David,2 Bruce Kahn,3 and Philippe A. Gallay1*

Department of Immunology, The Scripps Research Institute, La Jolla, California 92037,1 Center for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, B-3000 Leuven, Belgium,2 Department of Obstetrics and Gynecology, Scripps Clinic, La Jolla, California 920373

Received 20 June 2006/ Accepted 11 October 2006

Although the transport of human immunodeficiency virus type 1 (HIV-1) through the epithelium is critical for HIV-1 colonization, the mechanisms controlling this process remain obscure. In the present study, we investigated the transcellular migration of HIV-1 as a cell-free virus through primary genital epithelial cells (PGECs). The absence of CD4 on PGECs implicates an unusual entry pathway for HIV-1. We found that syndecans are abundantly expressed on PGECs and promote the initial attachment and subsequent entry of HIV-1 through PGECs. Although CXCR4 and CCR5 do not contribute to HIV-1 attachment, they enhance viral entry and transcytosis through PGECs. Importantly, HIV-1 exploits both syndecans and chemokine receptors to ensure successful cell-free transport through the genital epithelium. HIV-1-syndecan interactions rely on specific residues in the V3 of gp120 and specific sulfations within syndecans. We found no obvious correlation between coreceptor usage and the capacity of the virus to transcytose. Since viruses isolated after sexual transmission are mainly R5 viruses, this suggests that the properties conferring virus replication after transmission are distinct from those conferring cell-free virus transcytosis through the genital epithelium. Although we found that cell-free HIV-1 crosses PGECs as infectious particles, the efficiency of transcytosis is extremely poor (less than 0.02% of the initial inoculum). This demonstrates that the genital epithelium serves as a major barrier against HIV-1. Although one cannot exclude the possibility that limited passage of cell-free HIV-1 transcytosis through an intact genital epithelium occurs in vivo, it is likely that the establishment of infection via cell-free HIV-1 transmigration is a rare event.

* Corresponding author. Mailing address: Department of Immunology, The Scripps Research Institute, IMM-9, 10550 North Torrey Pines Road, La Jolla, CA 92037. Phone: (858) 784-8180. Fax: (858) 784-8227. E-mail: gallay{at}scripps.edu.

{triangledown} Published ahead of print on 18 October 2006.

Journal of Virology, January 2007, p. 395-405, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01303-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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