title: Viral profiling identifies multiple subtypes of Kaposi's sarcoma.
abstract: Kaposi's sarcoma (KS), caused by KS-associated herpesvirus (KSHV), is the most common cancer among HIV-infected patients in Malawi and in the United States today. In Malawi, KSHV is endemic. We conducted a cross-sectional study of patients with HIV infection and KS with no history of chemo- or antiretroviral therapy (ART). Seventy patients were enrolled. Eighty-one percent had T1 (advanced) KS. Median CD4 and HIV RNA levels were 181 cells/mm(3) and 138,641 copies/ml, respectively. We had complete information and suitable plasma and biopsy samples for 66 patients. For 59/66 (89%) patients, a detectable KSHV load was found in plasma (median, 2,291 copies/ml; interquartile range [IQR], 741 to 5,623). We utilized a novel KSHV real-time quantitative PCR (qPCR) array with multiple primers per open reading frame to examine KSHV transcription. Seventeen samples exhibited only minimal levels of KSHV mRNAs, presumably due to the limited number of infected cells. For all other biopsy samples, the viral latency locus (LANA, vCyc, vFLIP, kaposin, and microRNAs [miRNAs]) was transcribed abundantly, as was K15 mRNA. We could identify two subtypes of treatment-naive KS: lesions that transcribed viral RNAs across the length of the viral genome and lesions that displayed only limited transcription restricted to the latency locus. This finding demonstrates for the first time the existence of multiple subtypes of KS lesions in HIV- and KS-treatment naive patients.
  
  
  OBJECTIVE
  KS is the leading cancer in people infected with HIV worldwide and is causally linked to KSHV infection. Using viral transcription profiling, we have demonstrated the existence of multiple subtypes of KS lesions for the first time in HIV- and KS-treatment-naive patients. A substantial number of lesions transcribe mRNAs which encode the viral kinases and hence could be targeted by the antiviral drugs ganciclovir or AZT in addition to chemotherapy.
authors.forename: Mina C
authors.initials: MC
authors.lastname: Hosseinipour
authors.affiliation: Department of Microbiology and Immunology, Curriculum in Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Sweet
authors.forename: Jie
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Kamuzu Central Hospital, Lilongwe, Malawi.
authors.forename: Dan
authors.initials: D
authors.lastname: Namarika
authors.affiliation: UNC Project, Lilongwe, Malawi.
authors.forename: Albert
authors.initials: A
authors.lastname: Mwafongo
authors.affiliation: Lighthouse Trust, Lilongwe, Malawi.
authors.forename: Michael
authors.initials: M
authors.lastname: Nyirenda
authors.affiliation: UNC Project, Lilongwe, Malawi.
authors.forename: Loreen
authors.initials: L
authors.lastname: Chiwoko
authors.affiliation: UNC Project, Lilongwe, Malawi.
authors.forename: Deborah
authors.initials: D
authors.lastname: Kamwendo
authors.forename: Irving
authors.initials: I
authors.lastname: Hoffman
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lee
authors.affiliation: Kamuzu Central Hospital, Lilongwe, Malawi.
authors.forename: Sam
authors.initials: S
authors.lastname: Phiri
authors.affiliation: Genedata, Basel, Switzerland.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Vahrson
authors.forename: Blossom
authors.initials: B
authors.lastname: Damania
authors.affiliation: ddittmer@med.unc.edu.
authors.forename: Dirk P
authors.initials: DP
authors.lastname: Dittmer
mesh_terms: D000328:Adult; D015992:Body Mass Index; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000145:classification* / Q000302:isolation & purification; D006801:Humans; D008295:Malawi / Q000453:epidemiology; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics; D012514:Sarcoma, Kaposi / Q000150:complications / Q000453:epidemiology / Q000821:virology*; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral