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.

Brief Report: De Novo Human Herpesvirus 8 Tumors Induced by Rituximab in Autoimmune or Inflammatory Systemic Diseases

“…Development of KS after treatment with RTX has been observed in HIV-associated multicentric Castleman's disease, but data are scarce regarding KS induced by RTX treatment in patients with autoimmune diseases, vasculitis, or humoral transplant rejection. Humoral immunity against HHV-8 infection has been described with minimal data on the role of HHV-8-neutralizing antibodies (13). The main target cells of HHV-8 are B cells and endothelial cells.…”

KSHV reduces autophagy in THP-1 cells and in differentiating monocytes by decreasing CAST/calpastatin and ATG5 expression

“…39 Furthermore, previous studies by our and other's laboratories have shown that KSHV inhibits monocytes differentiation into DCs. 43,68,69 Based on this knowledge, we next evaluated whether KSHV would reduce CAST and ATG5 also in primary monocytes and whether the impairment of their in vitro differentiation would be due to the autophagy inhibition.…”

Primary effusion lymphoma involving cerebrospinal fluid, deep cervical lymph nodes and adenoids. Report of a case supporting the lymphatic connection between brain and lymph nodes

“…In healthy persons the immune activation and specific responses to HHV8 infection are able to control the virus, but immunosupression from HIV‐1 infection or other causes underlies the development of HHV‐associated diseases (Kaposi sarcoma, PEL and Castleman's diseases). Latently infected naïve and IgM memory B cells are thought to be driven to a preterminal plasma cell stage of differentiation in PEL …”