Molecular virology of Kaposi's sarcoma–associated herpesvirus

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Abstract
Kaposi's sarcoma–associated herpesvirus (KSHV), the most recently discovered human tumour virus, is the causative agent of Kaposi's sarcoma, primary effusion lymphoma and some forms of Castleman's disease. KSHV is a rhadinovirus, and like other rhadinoviruses, it has an extensive array of regulatory genes obtained from the host cell genome. These pirated KSHV proteins include homologues to cellular CD21, three different β–chemokines, IL–6, BCL–2, several different interferon regulatory factor homologues, Fas–ligand ICE inhibitory protein (FLIP), cyclin D and a G–protein–coupled receptor, as well as DNA synthetic enzymes including thymidylate synthase, dihydrofolate reductase, DNA polymerase, thymidine kinase and ribonucleotide reductases. Despite marked differences between KSHV and Epstein–Barr virus, both viruses target many of the same cellular pathways, but use different strategies to achieve the same effects. KSHV proteins have been identified which inhibit cell–cycle regulation checkpoints, apoptosis control mechanisms and the immune response regulatory machinery. Inhibition of these cellular regulatory networks appears to be a defensive means of allowing the virus to escape from innate antiviral immune responses. However, due to the overlapping nature of innate immune and tumour–suppressor pathways, inhibition of these regulatory networks can lead to unregulated cell proliferation and may contribute to virus–induced tumorigenesis.