Molecular virology of Kaposi's sarcoma-associated herpesvirus.
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 beta-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 app ears 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.
Moore
P S
PS
School of Public Health and Department of Pathology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA. psm9@columbia.edu
Chang
Y
Y
D000818:Animals; D002453:Cell Cycle; D004854:Herpesvirus 4, Human / Q000235:genetics; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000276:immunology; D006801:Humans; D012514:Sarcoma, Kaposi / Q000276:immunology / Q000821:virology*; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism
D014764:Viral Proteins