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* Department of Medicine and
Department of Neurosurgery, Division of Infectious Diseases, School of Medicine and
Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104
During sexual transmission of HIV in women, the first cells likely to be infected are submucosal CD4+ T cells and dendritic cells of the lower genital tract. HIV is segregated from these target cells by an epithelial cell layer that can be bypassed even when healthy and intact. To understand how HIV penetrates this barrier, we identified a host protein, gp340, that is expressed on genital epithelium and binds the HIV envelope via a specific protein-protein interaction. This binding allows otherwise subinfectious amounts of HIV to efficiently infect target cells and allows this infection to occur over a longer period of time after binding. Our findings suggest a mechanism of viral entry during heterosexual transmission where HIV is bound to intact genital epithelia, which then promotes the initial events of infection. Understanding this step in the initiation of infection will allow for the development of tools and methods for blocking HIV transmission.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants AI50484, DE14825, and AI060505. The Cooperative Human Tissue Network is funded by the National Cancer Institute.
2 Current address: Department of Basic Sciences, College of Dentistry, New York University, 345 East 24th Street, Room 904 S, New York, NY 10010.
3 Address correspondence and reprint requests to Dr. Drew Weissman, University of Pennsylvania, 522B Johnson Pavilion, Philadelphia, PA 19104. E-mail address: dreww{at}mail.med.upenn.edu
4 Abbreviations used in this paper: LC, Langerhans cell; DC, dendritic cell; Env, envelope protein; DC-SIGN, DC-specific intercellular adhesion molecule-grabbing integrin; MR, mannose receptor; SAG, salivary agglutinin; PHA-blasts, PHA- and IL-2-stimulated PBMCs; TCID50, 50% tissue culture-infective dose; STD, sexually transmitted disease; SRCR, scavenger receptor cysteine-rich.
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