title: Induction of hyaluronan production by oncogenic KSHV and the contribution to viral pathogenesis in AIDS patients.
abstract: Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), malignancies arising primarily in immunocompromised patients particularly AIDS-patients, which still lack effective therapy. Hyaluronan (HA) is a large glucuronic acid and has been found closely related to multiple functions in cancer cells, although its role in viral oncogenesis remains largely unknown. Here we provide first evidence that KSHV de novo infection induces HA production from primary endothelial cells through upregulation of HA synthase gene 1 (Has1) and a multifunctional glycoprotein, CD147. Further data demonstrate that KSHV-induced HA production requires viral latent protein, LANA (in particular functional domain A) and MAPK/ERK signaling activities. In functions, HA production is necessary for KSHV/LANA-induced primary endothelial cell invasion, a hallmark feature for KS development. For clinical relevance, our data indicate that the KSHV+ group has higher levels of HA and Has1 activities in its plasma than the KSHV- group of cohort HIV-infected patients. Together, our findings provide innovative insights into the mechanisms of oncogenic virus activation of HA production and its role in virus-associated malignancy pathogenesis, which may help to develop novel therapeutic strategies by targeting HA and related signaling.
authors.affiliation: Research Center for Translational Medicine and Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China; Department of Medicine, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, 1700 Tulane Ave., New Orleans, LA 70112, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Dai
authors.affiliation: Research Center for Translational Medicine and Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China.
authors.forename: Yihan
authors.initials: Y
authors.lastname: Chen
authors.forename: Karlie
authors.initials: K
authors.lastname: Bonstaff
authors.forename: Lisa
authors.initials: L
authors.lastname: Doyle
authors.affiliation: Departments of Regenerative Medicine & Cell Biology, Medical University of South Carolina and Hollings Cancer Center, Charleston, SC 29425, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Toole
authors.affiliation: Department of Medicine, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, 1700 Tulane Ave., New Orleans, LA 70112, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Parsons
authors.affiliation: Research Center for Translational Medicine and Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China; Departments of Microbiology/Immunology/Parasitology, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, 1700 Tulane Ave., New Orleans, LA 70112, USA. Electronic address: zqin@lsuhsc.edu.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Qin
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism* / Q000821:virology*; D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000378:metabolism; D051926:Basigin / Q000378:metabolism; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006678:HIV / Q000378:metabolism / Q000472:pathogenicity; D019288:Herpesvirus 8, Human / Q000378:metabolism* / Q000472:pathogenicity*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000821:virology; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; C497886:BSG protein, human; D009687:Nuclear Proteins; C109540:latency-associated nuclear antigen; D051926:Basigin; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C523794:HAS1 protein, human; D000076002:Hyaluronan Synthases
keywords: CD147; Hyaluronan; KSHV; LANA
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