17th International AIDS Conference Mexico City, Mexico - August 13 - 18, 2008

DEVELOPMENT AND CHARACTERIZATION OF A HUMANIZED-CERVICOVAGINAL MURINE MODEL FOR THE STUDY OF HIV-1 TRANSMISSION AND INFECTION

Int Conf AIDS. 2008 Aug 13-18;17 Abstract No. MoAa0104

T. Kish-Catalone
DeSales University, Department of Natural Science, Center Valley, United States

BACKGROUND: A small animal model for the study of human immunodeficiency virus-1 (HIV-1) in human target cells is critical for the advancement of therapeutic and preventative strategies. The NOD/SCID-hu immunocompromised murine model reconstituted with human peripherial blood mononuclear cells (PBMC) is currently being developed for the preclinical safety and efficacy assessment of biologically active anti-HIV-1 agents. The objective of this study was to demonstrate microbicide-induced inflammation and toxicity, the recruitment of human PBMC into the cervicovaginal epithelia, and the utility of this model for determining the relationship between cervicovaginal toxicity and susceptibility to infection.

METHODOLOGY: Human PBMC were successfully engrafted into NOD/SCID animals using an intraperitoneal injection of 5 × 10⁷ PBMC. Animals were analyzed by fluorescence-activated cell sorter (FACS) analyses for evidence of specific immune cell populations in the blood circulation. Animals were also sacrificed at two-week intervals for 2 months post-injection and cervicovaginal tissues were harvested for immunohistochemical analyses of specific human immune cell populations.

RESULTS: Past studies demonstrated the presence of human immume cell populations in the peripheral blood of NOD/SCID-hu mice reconstituted with human PBMC. Immunohistochemical methods also detected infiltration of human CD45+ cells in the mouse spleens and for at least 2 months after reconstitution. In addition, examinations were conducted monitoring trafficking of human immune cell populations into the murine cervicovaginal mucosa.

CONCLUSION: The NOD/SCID human xenograft model may provide a unique small animal system for the study of HIV-1 transmission in tissue with human immune target cells, and for examining initial cell populations involved in the establishment of HIV-1 infection. Further, this model can be developed as an inexpensive, large-scale screening tool for assessing pre-clinical microbicide-induced damage to the cervicovaginal mucosa and for determining the efficacy of candidate compounds in an anatomically representative system.

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2008-08-13
MoAa0104

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