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

Kristen V. Khanna, Kevin J. Whaley, Larry Zeitlin, Thomas R. Moench, Karim Mehrazar, Richard A. Cone, Zhaohao Liao, James Hildreth, Timothy E. Hoen, Leonard Shultz, Richard B. Markham

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

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 β-cyclodextrin (β-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.

Original languageEnglish (US)
Pages (from-to)205-211
Number of pages7
JournalJournal of Clinical Investigation
Volume109
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Khanna, K. V., Whaley, K. J., Zeitlin, L., Moench, T. R., Mehrazar, K., Cone, R. A., Liao, Z., Hildreth, J., Hoen, T. E., Shultz, L., & Markham, R. B. (2002). Vaginal transmission of cell-associated HIV-1 in the mouse is blocked by a topical, membrane-modifying agent. Journal of Clinical Investigation, 109(2), 205-211. https://doi.org/10.1172/JCI200213236