title: Contribution of viral mimics of cellular genes to KSHV infection and disease.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV, also named Human herpesvirus 8 HHV-8) is the cause of Kaposi sarcoma (KS), the most common malignancy in HIV-infected individuals worldwide, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). KSHV is a double-stranded DNA virus that encodes several homologues of cellular proteins. The structural similarity between viral and host proteins explains why some viral homologues function as their host counterparts, but sometimes at unusual anatomical sites and inappropriate times. In other cases, structural modification in the viral proteins can suppress or override the function of the host homologue, contributing to KSHV-related diseases. For example, viral IL-6 (vIL-6) is sufficiently different from human IL-6 to activate gp130 signaling independent of the α subunit. As a consequence, vIL-6 can activate many cell types that are unresponsive to cellular IL-6, contributing to MCD disease manifestations. Here, we discuss the molecular biology of KSHV homologues of cellular products as conduits of virus/host interaction with a focus on identifying new strategies for therapy of KS and other KSHV-related diseases.
authors.affiliation: Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan. sakakibara@ragtime.biken.osaka-u.ac.jp.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Sakakibara
authors.affiliation: Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20982, USA. tosatog@mail.nih.gov.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tosato
mesh_terms: D005871:Castleman Disease / Q000209:etiology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006566:Herpesviridae Infections / Q000150:complications* / Q000235:genetics / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D054685:Lymphoma, Primary Effusion / Q000209:etiology*; D016328:NF-kappa B / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000209:etiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53