Vaginal transmission of cell-associated HIV-1 in the mouse is blocked by a topical, membrane-modifying agent
Kristen V. Khanna, … , Leonard Shultz, Richard B. Markham
Kristen V. Khanna, … , Leonard Shultz, Richard B. Markham
Published January 15, 2002
Citation Information: J Clin Invest. 2002;109(2):205-211. https://doi.org/10.1172/JCI13236.
View: Text | PDF
Article

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

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.

Authors

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

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
Progesterone treatment of C.B-17 SCID mice thins the vaginal epithelium....
Progesterone treatment of C.B-17 SCID mice thins the vaginal epithelium. Female C.B-17 scid/scid mice, or BALB/c mice (not shown) were given either saline or 2.5 mg Depo-Provera and euthanized after 7 days. Tissues were collected and processed as described in Methods. Tissue sections shown are hematoxylin and eosin–stained vaginal epithelium from (a) an untreated mouse in estrus (×120), (b) a progestin-treated mouse (×120), (c) normal human vagina (×50), and (d) normal human cervix (×160). While there are striking differences between the progestin-treated vaginal epithelium of a SCID mouse and the untreated, stratified, squamous vaginal epithelium (murine), the similarities in morphology and cellular architecture are apparent between the thin, columnar, progestin-treated, murine vaginal epithelium and the human, columnar, cervical epithelium.