Kaposi sarcoma (KS)-associated herpesvirus microRNA sequence analysis and KS risk in a European AIDS-KS case control study

欧洲艾滋病-卡波西肉瘤 (KS) 病例对照研究中的卡波西肉瘤 (KS) 相关疱疹病毒 microRNA 序列分析和 KS 风险

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作者:Vickie Marshall, Elisa Martró, Nazzarena Labo, Alex Ray, Dian Wang, Georginia Mbisa, Rachel K Bagni, Natalia Volfovsky, Jordi Casabona, Denise Whitby; EURO-SHAKS Study Group

Background

We recently identified polymorphisms in Kaposi sarcoma-associated herpesvirus (KSHV)-encoded microRNA (miRNA) sequences from clinical subjects. Here, we examine whether any of these may contribute to KS risk in a European AIDS-KS case-control study.

Conclusions

Patients with KS were more likely to have detectable viral loads than were controls without disease. Despite high conservation in KSHV miRNA-encoded sequences, polymorphisms were observed, including some that have been reported elsewhere. Some polymorphisms could affect mature miRNA processing and appear to be associated with KS risk.

Methods

KSHV load in peripheral blood was determined by real-time quantitative polymerase chain reaction. Samples that had detectable viral loads were used to amplify the 2.8-kb miRNA encoding region plus a 646-bp fragment of the K12/T0.7 gene. Additionally, we characterized an 840-bp fragment of the K1 gene to determine KSHV subtypes.

Results

KSHV DNA was detected in peripheral blood mononuclear cells of 49.6% of case patients and 6.8% of controls, and viral loads tended to be higher in case patients. Sequences from the miRNA-encoding regions were conserved overall, but distinct polymorphisms were detected, some of which occurred in primary miRNAs, pre-miRNAs, or mature miRNAs. Conclusions: Patients with KS were more likely to have detectable viral loads than were controls without disease. Despite high conservation in KSHV miRNA-encoded sequences, polymorphisms were observed, including some that have been reported elsewhere. Some polymorphisms could affect mature miRNA processing and appear to be associated with KS risk.

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