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 3

Options: View larger image (or click on image) Download as PowerPoint
Human cells do not populate the HuPBL-SCID mouse vagina. HuPBMCs were tr...
Human cells do not populate the HuPBL-SCID mouse vagina. HuPBMCs were transplanted into the peritoneal cavity of progesterone-treated, female HuPBL-SCID mice. Tissue sections of the vagina, spleen, and peritoneal mesentery taken 7 days later were hybridized with a human pan-centromere probe to detect human cells. Whereas abundant human cells were found in the peritoneal mesentery (a), and occasionally in the spleen (not shown), no human cells were detected in the vaginal tissues (b). No human cells were detected in an additional negative control, a mouse that did not receive a HuPBL transplant (not shown).