Viral Replication and Pathogenicity
Session Day and Time: Thursday 1:30 - 3:30 pm
Room: Hall A
Background: Emergence of X4 HIV strains occurs late in the course of HIV infection, suggesting that a selective pressure interferes with the switch from CCR5 to CXCR4 coreceptor tropism. We hypothesized that SDF-1 production could be involved in this process, and to this aim we have analyzed the expression of SDF-1 in lymph nodes and cultured dendritic cells.
Methods: Characterization of SDF-1 producing cells in paraffin-embedded and frozen sections in normal tonsils and lymph nodes from HIV-infected patients at different clinical stages was analyzed by immunohistochemistry and in situ hybridization techniques, using specific antibodies against SDF-1, CD1a, and dendritic cells antigens. Expression of SDF-1 was assessed in an in vitro model of dendritic cell differentiation using flow cytometry, western blot, and RT-PCR techniques.
Results: SDF-1 was widely expressed in endothelial cells and also by dendritic cells (CD1a+) in tonsil cripts and in the parafollicular compartment of lymph nodes. SDF-1 expression was documented in differentiated dendritic cells in vitro. In contrast, neither resting nor activated T-cells produced SDF-1.
Conclusions: These results suggest that the presence of SDF-1 producing cells in the parafollicular T-cell region and the SDF expression in endothelial and dendritic cells could account for the low propagation of X4 HIV strains in early stages of infection in which lymphoid organs structure is still conserved.