Vaginal transmission of cell-associated HIV-1 in the mouse is blocked by a topical, membrane-modifying agent

• Published in: The Journal of clinical investigation Vol. 109; no. 2; pp. 205 - 211
• Main Authors: Khanna, Kristen V, Whaley, Kevin J, Zeitlin, Larry, Moench, Thomas R, Mehrazar, Karim, Cone, Richard A, Liao, Zhaohao, Hildreth, James E K, Hoen, Timothy E, Shultz, Leonard, Markham, Richard B
• Format: Journal Article
• Language: English
• Published: United States 01.01.2002
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Topical; Animals; b-Cyclodextrin; beta-Cyclodextrins; Cell Movement; Cyclodextrins - administration & dosage; Cyclodextrins - adverse effects; Cyclodextrins - pharmacology; Disease Models, Animal; Epithelium; Excipients - administration & dosage; Excipients - adverse effects; Excipients - pharmacology; Female; HeLa Cells; HIV Infections - prevention & control; HIV Infections - transmission; HIV Infections - virology; HIV-1 - physiology; Human immunodeficiency virus 1; Humans; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - transplantation; Leukocytes, Mononuclear - virology; Lymph Nodes; Mice; Mice, SCID; Peritoneal Cavity; Progesterone - pharmacology; Vagina - virology
• ISSN: 0021-9738
• DOI: 10.1172/JCI0213236

Because both HIV-1 virions and HIV-infected cells are present in the semen and cervical mucus of infected individuals, HIV-1 prevention strategies must consider both cell-free and cell-associated virus. Antibodies that target HIV-1 virions have been shown to prevent vaginal transmission of cell-free virus in macaques, but since cell-associated transmission has not been reliably demonstrated in this model system, no strategies to prevent such transmission have been tested. We have employed a mouse model in which SCID mice carry human peripheral blood leukocytes (HuPBLs). In these mice, vaginal transmission of cell-associated, but not cell-free, HIV-1 transmission occurs, mediated by transepithelial migration of HIV-infected cells. Topical application of beta-cyclodextrin (beta-CD), a cholesterol-sequestering agent that interferes with cell migration and budding of virus from lipid rafts, blocks transmission of cell-associated HIV-1. The HuPBL-SCID model of vaginal HIV-1 transmission should prove useful for investigating cell-associated HIV-1 transmucosal HIV-1 transmission, as well as for screening reagents for their potential efficacy in preventing sexual HIV-1 transmission.