Sequence analysis of Kaposi sarcoma–associated herpesvirus (KSHV) microRNAs in patients with multicentric Castleman disease and KSHV-associated …
A Ray, V Marshall, T Uldrick, R Leighty… - The Journal of …, 2012 - academic.oup.com
The Journal of infectious diseases, 2012•academic.oup.com
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 …
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 …
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 χ2 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.
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