Kaposi’s Sarcoma-Associated Herpesvirus Subversion of the Anti-Inflammatory Response in Human Skin Cells Reveals Correlates of Latency and Disease Pathogenesis

Figure 9

Hypothetical model of immunophysiologic mechanisms that control transmission of KSHV from latently infected cellular reservoirs to cells within skin. (1) Chronic activation of NF-κB in the skin induces expression of adhesion molecules on the surfaces of endothelial cells, increased vascular permeability, and secretion of inflammatory cytokines and chemokines by melanocytes and other resident cells of the skin, (2) recruitment of immune cells and other KSHV-infected monocytes to the vascular endothelium, and (3) extravasation of infected cells from the blood vessels into the underlying dermis, where virus may be transmitted to vascular endothelial cells through cell-to-cell contact or other mechanisms. (4) Accumulation of cell-free and KSHV-infected cells at the superficial dermis, where they interact with and infect resident melanocytes and keratinocytes in the basal membrane.