Kaposi's sarcoma associated herpes virus (KSHV/HHV 8): epidemiology, molecular biology and tissue distribution.

Introduction Although first described in 1872, Kaposi's sarcoma remains a neoplasm of uncertain histiogenesis.' The lesion is considered by some experts to be a vascular neoplasm and by others, a reactive vasoformative condition. Currently, the debate still rages over the precise cell of origin of Kaposi's sarcoma-that is, whether it is of lymphatic or true endothelial cell origin. Clinically, Kaposi's sarcoma is often multifocal and the spindle cells of these individual lesions have been shown to be clonal in origin.2 It is also known that Kaposi's sarcoma lesions can regress spontaneously, especially when immunosuppressive treatment is discontinued, thereby suggesting that the growth of Kaposi's sarcoma is controlled by host factors. In addition, at least one group has observed regression of Kaposi's sarcoma lesions when patients are treated with the anti-herpes viral drug Foscarnet.3 The role of cytokines has also been explored, as has the contribution of the HIV Tat protein which may act in a synergistic manner (see later). Epidemiological evidence suggests an infectious aetiology for Kaposi's sarcoma, which is supported by the clustering of the disease in well-defined populations (men with AIDS and homosexual men) and its relation to immunosuppression.4 Many agents have been investigated as possible aetiological factors, including human papilloma virus, cytomegalovirus and Epstein-Barr virus (EBV), but no convincing association has ever been established. Kaposi's sarcoma associated herpes virus (KSHV)/human herpes virus type 8 (HHV8) In 1994, Chang et ar documented the presence of a previously undescribed virus in Kaposi's sarcoma tissue samples (fig 1). This Kaposi's sarcoma associated herpes virus (HHV8) was discovered using representation difference analysis which permits the discrimination of DNA sequences which are present in tumour tissue from ones that are absent in normal DNA from the same patient. The newly described virus shows similarity to two other gamma herpes viruses-herpes virus saimiri (HVS) and EBV.6 Viral genetic analysis demonstrates that the agent is a gamma II herpes virus (genus Rhadinovirus) and is the first member of this genus known to infect humans (fig 2). HHV8 has been partially sequenced recently and many regions show sequence homology at the DNA level to both EBV and HVS.