Human herpesviruses: Malignant lymphoma

The human gammaherpesviruses, Epstein-Barr virus (EBV, or HHV4) and Kaposi sarcoma-associated herpesvirus (KSHV, or HHV8), are associated with lymphoma. EBV was first discovered in the 1960s in association with Burkitt lymphomas arising in sub-Saharan Africa, while the discovery of KSHV in 1994 was associated with Kaposi sarcoma tumors and driven by the AIDS epidemic. While EBV infection is ubiquitous, KSHV is restricted to certain populations. EBV-associated lymphoproliferative diseases are likewise more common than KSHV-associated lymphoproliferative disease. These two herpesviruses nonetheless share many characteristics. Particularly relevant to lymphoma and lymphoproliferative disease is the ability of these two viruses to infect and establish a reservoir of infection in lymphocytes. Whereas some herpesviruses establish latency in nondividing terminally differentiated cells such as neurons, the gammaherpesviruses establish latency in lymphocytes. The gammaherpesviruses have evolved mechanisms for persisting as extrachromosomal genomes in dividing cells. These cells may be driven to proliferate or be protected from cell death pathways by viral gene expression. The result may be a self-limited lymphoproliferation that establishes or maintains a reservoir of latently infected cells or, under certain circumstances, a malignant lymphoproliferation.