Speaker
Description
Following initial infection, HIV spreads to regional lymph nodes within 3–6 days, and systemic dissemination occurs within 6–25 days. However, these experimental findings do not align with the results of current HIV mathematical models, which show that while viral dissemination in the blood occurs within 6–25 days, the virus appears in the lymph nodes after a delay of 50 days. We hypothesize that this discrepancy occurs because current HIV mathematical models do not account for the presence of follicular dendritic cells (FDCs), which stabilize HIV and facilitate its import into the lymph nodes. FDCs are located in the center of the B cell follicle germinal center (GC). FDCs release chemokines to attract B and T cells into the GCs, thereby facilitating HIV infection. The HIV on FDCs composes a long-term reservoir, with a half-life of roughly 21-22 months. FDCs play a key role in supporting HIV, and mathematical models have been developed to understand viral dynamics in lymphoid tissue. However, these models either fail to account for the virus on FDCs or lack spatial dynamics, causing discrepancies with experimental data. This study presents a modified HIV model that includes FDCs and spatial dynamics. Using reaction-diffusion equations for HIV infection dynamics on the fully reconstructed 3D geometry of a murine lymph node with connectivity to blood and fluid lymph, we predict the distribution of free virus in FDCs, lymph, blood, and both uninfected and infected CD4+ T cells over time and space. Incorporating FDCs reduces the 50-day delay in virus presence in lymph nodes to 10 days, aligning the model with experimental findings. This improves the model's accuracy and provides valuable insights into HIV dynamics in lymph nodes, with potential research and treatment implications.
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