Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes
Fig 5
Model of FDC HIV retention, transfer to T cells and sCD21-Ig purging.
Schematic model. HIV is captured and subsequently cycled by complement receptor 2 (CD21) on the follicular dendritic cell (FDC). The HIV virion resides in the protective recycling endosome of the FDC. Upon emerging from the endosome at the cell surface, HIV can infect surrounding T follicular helper (Tfh) cells that have been attracted to the FDC by a CXCL13 gradient. Infection occurs through binding of CD4 and either CXC-chemokine receptor 4 (CXCR4) or CC-chemokine receptor 5 (CCR5) as a co-receptor by gp120. The soluble CD21 receptor fusion protein (sCD21-Ig) competes with the CD21 on the FDC for binding of complement C3d on the virion. This facilitates the release of the virion and makes it available for degradation by other cells. To prevent infection of T cells at this stage the treatment should be combined with broadly neutralizing antibodies (bNab).