These large viruses (diameter 125–200 nm) contain a linear genome of double-stranded DNA (125–240 kbp) and have a capsid with icosahedral symmetry surrounded by an outer lipid-containing envelope. Herpesviruses typically cause acute infections followed by latency and eventual recurrence in each host, including humans.
In humans, herpesviruses have been linked to several specific types of tumors. Herpesvirus EBV causes acute infectious mononucleosis when it infects B lymphocytes of susceptible humans. Normal human lymphocytes have a limited life span in vitro, but EBV can immortalize such lymphocytes into lymphoblast cell lines that grow indefinitely in culture.
EBV is etiologically linked to Burkitt lymphoma, a tumor most commonly found in children in central Africa; to nasopharyngeal carcinoma, more common in Cantonese Chinese and Alaskan Eskimos than other populations; to posttrans plant lymphoproliferative disorders in immunocompromised hosts; and to Hodgkin’s disease. These tumors usually contain EBV viral DNA (both integrated and episomal forms) and viral antigens.
EBV encodes a viral oncogene protein (LMP1) that mimics an activated growth factor receptor. LMP1 is able to trans form rodent fibroblasts and is essential for transformation of B lymphocytes. Several EBV-encoded nuclear antigens (EBNAs) are necessary for immortalization of B cells; EBNA1 is the only viral protein consistently expressed in Burkitt lymphoma cells. EBV is very successful at avoiding immune elimination; this may be due in part to the function of EBNA1 in inhibition of antigen processing to allow infected cells to escape killing by cytotoxic T lymphocytes.
Malaria may be a cofactor for African Burkitt lymphoma. Most of those tumors also show characteristic chromosomal translocations between the c-myc gene and immunoglobulin loci, leading to the constitutive activation of myc expression. Consumption of salted or dried fish may be a dietary cofactor in EBV-related nasopharyngeal carcinoma. EBV-associated posttransplant lymphoproliferative disorders are more common in highly immunosuppressed transplant patients and can be detected earlier by screening for EBV in the blood.
Kaposi sarcoma-associated herpesvirus, also known as human herpesvirus 8 (KSHV/HHV8), is not as ubiquitous as most other human herpesviruses. It is believed to be the cause of Kaposi sarcoma, primary effusion lymphoma, and multi centric Castleman disease, a lymphoproliferative disorder. KSHV has a number of genes related to cellular regulatory genes that may stimulate cellular proliferation and modify host defense mechanisms.
Some herpesviruses are associated with tumors in lower animals. Marek disease is a highly contagious lymphoproliferative disease of chickens that can be prevented by vaccination with an attenuated strain of Marek disease virus. The prevention of cancer by vaccination in this case establishes the virus as the causative agent and suggests the possibility of a similar approach to prevention of human tumors with a virus as a causative agent. Other examples of herpesvirus induced tumors in animals include lymphomas of certain types of monkeys and adenocarcinomas of frogs. The simian viruses cause inapparent infections in their natural hosts but induce malignant T-cell lymphomas when transmitted to other species of monkeys
