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14th International AIDS ConferenceBarcelona, Spain — July 7-12, 2002 |
Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. MoOrA1002
BACKGROUND: Three unique patients (R1, R2, and R3) in the Baltimore ALIVE cohort progressed to AIDS very rapidly and disease progression was associated with rapid depletion of both CD4+ and CD8+ T cell populations. The HIV-1 isolated from these patients at serum conversion was characterized in vitro as Macrophage-tropic and syncytium-inducing (SI).
METHODS: The rapid decline of both CD4+ and CD8+ T cells (or loss of homeostasis of T cells) suggested that these isolates infect and impair the thymus functions efficiently. To test this hypothesis we characterized the coreceptor usage and tropism of these isolates in vitro and ex vivo, and examined their replication and pathogenicity in the human fetal thymus organ culture (HF-TOC) model.
RESULTS: Our data demonstrated that the three virus isolates replicated with a similar kinetics as typical X4 or R5 isolates in PBMC, but very efficiently in HF-TOC and/or mediated rapid thymocyte depletion. In addition, the results demonstrated that all three isolates depleted both CD4 and CD8 T cells in activated PBMC, and in the thymus model.
CONCLUSIONS: The results suggest that thymic-tropism of transmitted HIV-1 isolates may contribute to rapid disease progression to AIDS. Thus, the HF-TOC assay provides a relevant model to correlate disease progression to AIDS with the thymus tropism in replication or pathogenicity of the transmitted HIV isolates.
Presenting author: Lishan Su
1UNC-Chapel Hill, Chapel Hill, United States.
2Johns Hopkins University, Baltimore, United States.
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MoOrA1002
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