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- Title
Sequence analysis of Kaposi sarcoma-associated herpesvirus (KSHV) microRNAs in patients with multicentric Castleman disease and KSHV-associated inflammatory cytokine syndrome.
- Authors
Ray A; Marshall V; Uldrick T; Leighty R; Labo N; Wyvill K; Aleman K; Polizzotto MN; Little RF; Yarchoan R; Whitby D; Ray, Alex; Marshall, Vickie; Uldrick, Thomas; Leighty, Robert; Labo, Nazzarena; Wyvill, Kathy; Aleman, Karen; Polizzotto, Mark N; Little, Richard F
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Publication
Journal of Infectious Diseases, 2012, Vol 205, Issue 11, p1665
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jis249