FR AA 0101
Visualizing initial SIV infection in female macaque models
Presented by Katharina Rothwangl (United States).
K. Rothwangl1, R. Veazey2, T. Hope1
1Northwestern Universities, Cellular and Molecular Biology, Chicago, United States, 2Tulane National Primate Research Center, Covington, United States
Background: Male to female transmission of HIV-1 is a complex process where the female genital tract is exposed to the virus, which crosses mucosal and epithelial barriers to establish infection. How HIV-1 initially establishes this early infection is poorly understood.
Methods: A female macaque model was utilized to track early infection events and to identify infected cells within the genital tract. Macaques were inoculated intra-vaginally with SIV vectors expressing fluorescent markers. The use of these replication deficient vectors enable us to specifically identify the first infected cells within the vaginal vault. Four days following inoculation, macaques were necropsied and the genital tracts were excised. The entire genital tract was imaged and stained for cellular markers and SIV vector infection.
Results: To date we have imaged five macaques and used three distinct SIV vectors. Our current efforts have revealed potential foci of infection within the genital tracts of infected macaques. These foci appear more frequently in the thinned vaginal epithelium of the Depo Provera treated macaque. The infected cells have a morphology and staining pattern consistent with CD4+ T cells. We are continuing this work to define the nature of these transduced cells within the Depo Provera vaginal challenge macaque model.
Conclusions: We have potentially identified the initial infected cells within the female macaque genital tissue. We speculate these foci may be responsible for establishing infection in sexual transmission. Identification of the initial targets of infection after sexual exposure will be invaluable in the development of protective interventions such as vaccines and microbicides.