A Review of the Epidemiology and the Mechanisms Underlying KSHV ‐induced Malignancies

Abstract

Kaposi's sarcoma herpesvirus (KSHV), also called human herpesvirus‐8 (HHV‐8), is believed to be the infectious causative agent of Kaposi's sarcoma and two other rare acquired immune deficiency syndrome (AIDS)‐associated neoplastic diseases. KSHV is relatively frequent in some countries of the Mediterranean area, and quite common in sub‐Saharan and South Africa, but rare in most other parts of the world. The virus is transmitted through sexual contact among adults. However, in endemic countries, the mode of transmission is most probably via behavioural practices using saliva from mother to child and between siblings. KSHV persists in infected cells in a latent episomal form expressing only a small number of genes to escape immune surveillance. These genes play a significant role in viral persistence and development of malignancy. A small number of KSHV‐infected cells undergo spontaneous lytic reactivation to ensure the production of new virions and provide inflammatory cytokines that participate in development of cancer. Key concepts: KSHV is a γ2‐herpesvirus (Rhadinovirus) that causes Kaposi sarcoma, Primary effusion lymphoma and Multicentric Castleman's disease mainly in immunocompromised individuals, e.g. AIDS patients. Similarly to the other herpesviruses KSHV has two phases of replication, latent and lytic. In malignancies, the virus is detected mainly in latent state, where only few proteins are expressed. Small number of infected cells undergo spontaneous lytic reactivation producing both, new virions for infecting new cells and inflammatory cytokines, which contribute to tumourigenesis through a paracrine mechanism. KSHV expresses several genes that play a role in inhibition of apoptosis (vFLIP, vBCL2), progression of cell cycle (vCYC, LANA), stimulation of cytokine production and angiogenesis (vGPCR, vFLIP, vIL‐6, K15). The prevalence of KSHV is low in most parts of the world, but higher in Mediterranean area and highest in Africa. KSHV‐induced malignancies are rare even in areas with high KSHV prevalence. KSHV is transmitted mainly by sexual contact among adults and via behavioural practices using saliva from mother to child and between siblings in endemic countries.