title: Sequence analysis of Kaposi sarcoma-associated herpesvirus (KSHV) microRNAs in patients with multicentric Castleman disease and KSHV-associated inflammatory cytokine syndrome.
abstract: BACKGROUND
  Kaposi sarcoma-associated herpesvirus (KSHV) encodes 12 pre-microRNAs that yield 25 mature microRNAs. We previously reported phylogenetic analysis of the microRNA-coding region of KSHV from Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD) patients. We observed a high level of conservation for most sequences but also a divergent cluster of 5 KSHV sequences, including 2 from MCD patients.
  
  
  METHODS
  KSHV microRNA sequences from 23 MCD patients and 7 patients with a newly described KSHV-associated inflammatory cytokine syndrome (KICS) were examined by amplification, cloning, and sequencing of a 646-bp fragment of K12/T0.7 encoding microRNA-K12-10 and microRNA-K12-12 and a 2.8-kbp fragment containing the remaining 10 pre-microRNAs.
  
  
  RESULTS
  Phylogenetic analysis showed a distinct variant cluster consisting exclusively of MCD and KICS patients in all trees. Pearson χ(2) analysis revealed that 40 single-nucleotide polymorphisms (SNPs) at various loci were significantly associated with MCD and KICS risk. Cluster analysis of these SNPs generated several combinations of 3 SNPs as putative indicators of MCD and KICS risk.
  
  
  CONCLUSIONS
  These findings show that MCD and KICS patients frequently have unusual KSHV microRNA sequences and suggest an association between the observed sequence variation and risk of MCD and KICS.
authors.affiliation: National Cancer Institute, Frederick, MD, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Ray
authors.forename: Vickie
authors.initials: V
authors.lastname: Marshall
authors.forename: Thomas
authors.initials: T
authors.lastname: Uldrick
authors.forename: Robert
authors.initials: R
authors.lastname: Leighty
authors.forename: Nazzarena
authors.initials: N
authors.lastname: Labo
authors.forename: Kathy
authors.initials: K
authors.lastname: Wyvill
authors.forename: Karen
authors.initials: K
authors.lastname: Aleman
authors.forename: Mark N
authors.initials: MN
authors.lastname: Polizzotto
authors.forename: Richard F
authors.initials: RF
authors.lastname: Little
authors.forename: Robert
authors.initials: R
authors.lastname: Yarchoan
authors.forename: Denise
authors.initials: D
authors.lastname: Whitby
mesh_terms: D005871:Castleman Disease / Q000821:virology*; D016000:Cluster Analysis; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005260:Female; D006566:Herpesviridae Infections / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D010802:Phylogeny; D017421:Sequence Analysis; D012689:Sequence Homology, Nucleic Acid
chemical_list: D004279:DNA, Viral; D035683:MicroRNAs