Professional antigen presenting cells in human herpesvirus 8 infection

Abstract

Professional antigen presenting cells (APC), i.e., dendritic cells (DC), monocytes/macrophages, and B lymphocytes, are critically important in the recognition of an invading pathogen and presentation of antigens to the T cell-mediated arm of immunity. Human herpesvirus 8 (HHV-8) is one of the few human viruses that primarily targets these APC for infection, altering their cytokine profiles, manipulating their surface expression of MHC molecules, and altering their ability to activate HHV-8-specific T cells. This could be why T cell responses to HHV-8 antigens are not very robust. Of these APC, only B cells support complete, lytic HHV-8 infection. However, both complete and abortive virus replication cycles in APC could directly affect viral pathogenesis and progression to Kaposi's sarcoma (KS) and HHV-8-associated B cell cancers. In this review, we discuss the effects of HHV-8 infection on professional APC and their relationship to the development of KS and B cell lymphomas.

Keywords: B lymphocytes; CD4 and CD8 T lymphocytes; Kaposi's sarcoma; dendritic cells; human herpesvirus 8; monocytes/macrophages; multicentric Castleman's disease; primary effusion lymphoma.

Figure 1

HHV-8 targets B cell subpopulations for infection. The B cell target for HHV-8 infection is unknown. However, evidence suggests that naïve and/or IgM memory B cell subsets are susceptible to HHV-8 infection. HHV-8 is endocytosed after binding to cell surface entry receptors. The virus then enters latency (left) or initiates lytic replication (Rappocciolo et al., 2008). Latently infected cells drive differentiation toward a plasmablast phenotype that is responsive to the proliferative cytokine, IL-6. The alternative pathway is the entry of HHV-8 into the lytic cycle to begin transcription of lytic-associated proteins in activated B cells (red outline). The lytic cycle may stop prior to virion production, resulting in an abortive replicative cycle as seen in DC, endothelial cells, and fibroblasts. The virus in these cells likely enters latency or may result in B cell apoptosis. Some cells, however, will support full lytic cycle replication, resulting in lytic protein synthesis, and increases in viral DNA that correspond to infectious HHV-8 progeny and subsequent release through cell lysis.