title: Viral interleukin-6: role in Kaposi's sarcoma-associated herpesvirus: associated malignancies.
abstract: Viral interleukin-6 (vIL-6) is a product of Kaposi's sarcoma-associated herpesvirus (KSHV) expressed in latently infected cells and to a higher degree during viral replication. A distinctive feature of vIL-6 is the ability to directly bind and activate gp130 signaling in the absence of other receptor subunits. Secretion of vIL-6 is generally poor, but vIL-6 can activate gp130 from inside the cell. Due to the wide cell distribution of gp130, vIL-6 has the potential to induce a wide range of biological effects. Expression of vIL-6 is variable in KSHV-associated Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD), and in a newly described MCD-like systemic inflammatory syndrome observed in human immunodeficiency virus-positive patients. PEL effusions usually contain vIL-6 at high concentrations; since vIL-6 induces vascular endothelial growth factor, vIL-6 likely contributes to vascular permeability and formation of PEL effusions. Lymph nodes affected with MCD contain vIL-6-positive cells, and vIL-6 levels rise in conjunction with flares of the disease and likely contribute to symptoms of inflammation. The development of vIL-6 inhibitors is a potentially important advance in the treatment of KSHV-associated malignancies where vIL-6 is expressed.
authors.affiliation: Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Sakakibara
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tosato
mesh_terms: D000818:Animals; D005871:Castleman Disease / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D054685:Lymphoma, Primary Effusion / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D012514:Sarcoma, Kaposi / Q000378:metabolism* / Q000473:pathology / Q000821:virology
chemical_list: D015850:Interleukin-6