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5th International Workshop on HIV Drug Resistance & Treatment Strategies4-8 June 2001, Scottsdale, Arizona |
OBJECTIVE: To develop an animal model of vaginal transmission of HIV-1 for the evaluation of vaginal microbicides.
METHODS: Vaginal infection was performed in SCID mice reconstituted with 4×107 human peripheral blood lymphocytes PBL (hu-PBL-SCID) by a non-invasive vaginal administration of human PBLs previously infected in vitro with a non-syncytium (NSI) strain of HIV-1 (SF162). We also examined in vivo lymphocyte migration using fluorescently labelled human lymphocytes. Percentage of CD4+ T cells, plasma viral load and p24 antigen detection were evaluated by using FACS analysis, the Amplicor HIV-1 monitor kit and ELISA, respectively. Polymerase chain reaction (PCR) analysis was performed on DNA extracted from spleen and lymph nodes. For in vivo migration of labelled lymphocytes, the mice were sacrificed after 4, 24 and 48 h, vagina and local lymph nodes were removed, snap frozen with OCT, sectioned, and examined by fluorescent microscopy and FACS.
RESULTS: HIV transmission was established by using NSI virus-infected cells inoculated vaginally, as shown by FACS, HIV-viral load, p24, and PCR results. Labelled cells were easily located within the vaginal tissues after 4 h. However, few or no cells could be identified after 24 or 48 h at the vaginal level, whereas the labelled cells could be detected at the level of regional lymph nodes.
CONCLUSION: Because of its simplicity and practical features compared to other animal models, the vaginal HIV-infected hu-SCID mouse model may prove useful to test the activity of compounds against cell associated HIV and, possibly, other sexually transmitted diseases.
PRESENTING AUTHOR: S Vella
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