Autopsy Study Defines Composition and Dynamics of the HIV-1 Reservoir after Allogeneic Hematopoietic Stem Cell Transplantation with CCR5Δ32/Δ32 Donor Cells.

Allo-HSCT with CCR5Δ32/Δ32 donor cells is the only curative HIV-1 intervention. We investigated the impact of allo-HSCT on the viral reservoir in PBMCs and post-mortem tissue in two patients. IciS-05 and IciS-11 both received a CCR5Δ32/Δ32 allo-HSCT. Before allo-HSCT, ultrasensitive HIV-1 RNA quantification; HIV-1-DNA quantification; co-receptor tropism analysis; deep-sequencing and viral characterization in PBMCs and bone marrow; and post-allo-HSCT, ultrasensitive RNA and HIV-1-DNA quantification were performed. Proviral quantification, deep sequencing, and viral characterization were done in post-mortem tissue samples. Both patients harbored subtype B CCR5-tropic HIV-1 as determined genotypically and functionally by virus culture. Pre-allo-HSCT, HIV-1-DNA could be detected in both patients in bone marrow, PBMCs, and T-cell subsets. Chimerism correlated with detectable HIV-1-DNA LTR copies in cells and tissues. Post-mortem analysis of IciS-05 revealed proviral DNA in all tissue biopsies, but not in PBMCs. In patient IciS-11, who was transplanted twice, no HIV-1-DNA could be detected in PBMCs at the time of death, whereas HIV-1-DNA was detectable in the lymph node. In conclusion, shortly after CCR5Δ32/Δ32, allo-HSCT HIV-1-DNA became undetectable in PBMCs. However, HIV-1-DNA variants identical to those present before transplantation persisted in post-mortem-obtained tissues, indicating that these tissues play an important role as viral reservoirs.

Various Tastes of Sugar: The Potential of Glycosylation in Targeting and Modulating Human Immunity via C-Type Lectin Receptors.

C-type lectin receptors (CLRs) are important in several immune regulatory processes. These receptors recognize glycans expressed by host cells or by pathogens. Whereas pathogens are recognized through their glycans, which leads to protective immunity, aberrant cellular glycans are now increasingly recognized as disease-driving factors in cancer, auto-immunity, and allergy. The vast variety of glycan structures translates into a wide spectrum of effects on the immune system ranging from immune suppression to hyper-inflammatory responses. CLRs have distinct expression patterns on antigen presenting cells (APCs) controlling their role in immunity. CLRs can also be exploited to selectively target specific APCs, modulate immune responses and enhance antigen presentation. Here we will discuss the role of glycans and their receptors in immunity as well as potential strategies for immune modulation. A special focus will be given to different dendritic cell subsets as these APCs are crucial orchestrators of immune responses in infections, cancer, auto-immunity and allergies. Furthermore, we will highlight the potential use of nanoscale lipid bi-layer structures (liposomes) in targeted immunotherapy.