Complement Receptor 3 Mediates HIV-1 Transcytosis across an Intact Cervical Epithelial Cell Barrier: New Insight into HIV Transmission in Women
Christopher J. Day, Rachael L. Hardison, Belinda L. Spillings, Jessica Poole, Joseph A. Jurcisek, Johnson Mak, Michael P. Jennings, Jennifer L. Edwards
Abstract
In women, the lower female reproductive tract is the primary site for HIV infection. How HIV traverses the epithelium to infect CD4 T cells in the submucosa is ill-defined. Cervical epithelial cells have a protein called CR3 on their surface. We show that HIV-1 binds to CR3 with high affinity and that this interaction is necessary and sufficient for HIV adherence to, and transcytosis across, polarized, human primary cervical epithelial cells. This suggests a unique role for CR3 on epithelial cells in dually facilitating HIV-1 attachment and entry. The HIV-CR3 interaction may constitute an efficient pathway for HIV delivery to subepithelial lymphocytes following virus transmission across an intact cervical epithelial barrier. Strategies with potential to prevent transmission via this pathway are presented.