Women are at risk of infection from HIV-positive male partners not only because they can become exposed to free viral particles, but also because infected cells, primarily macrophages and T cells, occur in the semen of infected men.
The relative importance of cell-associated and cell-free virus for male-to-female transmission of AIDS has been controversial, and even the route by which cell-associated virus reaches new target cells is far from clear.
Arguing that these difficulties reflect the absence of a suitable in vivo model system for this route, Khanna et al. have explored the course of infection following exposure to cell-associated HIV in the mouse.
Normal mouse leukocytes are unaffected by the presence of HIV, but the authors show that female SCID mice reconstituted with human leukocytes can be infected after intravaginal inoculation with peripheral blood leukocytes (PBLs) derived from HIV-positive individuals.
In this system, free virus is not transmitted, but PBL-associated HIV can be found in the female animal's lymph nodes within several hours of inoculation with infected cells. Within two weeks, this cell-associated virus is transmitted to previously uninfected cells. Khanna et al. find that transmission depends on pretreatment with progesterone, which thins the vaginal epithelium, raising the possibility that hormone treatment or cyclical changes in hormones could affect the efficiency of infection by cell-associated virus in women as well.
The authors also show that cyclodextrin, an agent that disrupts lipid rafts in cell membranes, prevents HIV transmission in this system. Several mechanisms for this effect could be envisioned and, while these remain to be resolved, the finding establishes that the mouse model system can be exploited to test the effects of various drugs on cell-associated HIV transmission.
Journal of Clinical Investigation