The human γ-HVs are able to establish a lifelong, persistent infection that is largely clinically inapparent within the immunocompetent host. However, when these viruses are not kept in check, a variety of lymphoproliferative and neoplastic disorders result that will be detailed elsewhere within this volume. In brief, for HHV-8, also known as Kaposi's sarcoma-associated herpesvirus (KSHV), these neoplasias include Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL). HHV-4, or Epstein–Barr virus (EBV), has been etiologically associated with infectious mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma (NPC), Hodgkin's disease, hemophagocytic lymphohistiocytosis syndrome and some gastric cancers. Through coevolution with their hosts, these viruses have acquired a number of genes that act to set a fine balance between the uncontrolled, virally driven cellular proliferation seen in the immunocompromised host and complete elimination of infected cells by the immune responses. Several of these gene products cause selective suppression of normal immune system functioning and allow for an apathogenic, persistent infection.
Immune system overview
The immune system provides multiple mechanisms of protection from invading pathogens, whether viral, bacterial or parasitic. These immune responses include both broad spectrum, innate responses and highly specific, adaptive responses. Mechanisms of the innate response include the production of viral replication blocking interferons, opsonization and lysis by the complement cascade and natural antibodies, apoptosis, as well as clearance of infection by natural killer (NK) cells, macrophages, neutrophils and T-cells.