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: Alex Ray, Vickie Marshall, Thomas Uldrick, Robert Leighty, Nazzarena Labo, Kathy Wyvill, Karen Aleman, Mark N Polizzotto, Richard F Little, Robert Yarchoan, Denise Whitby
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 205 Issue 11 Pg. 1665-76 (Jun 2012) ISSN: 1537-6613 [Electronic] United States
• PMID: 22448005 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• DNA, Viral
• MicroRNAs

Topics

• Castleman Disease (virology)
• Cluster Analysis
• DNA, Viral (chemistry, genetics)
• Female
• Herpesviridae Infections (virology)
• Herpesvirus 8, Human (genetics, isolation & purification)
• Humans
• Male
• MicroRNAs (genetics)
• Phylogeny
• Sequence Analysis
• Sequence Homology, Nucleic Acid