Emerging Themes from EBV and KSHV microRNA Targets.docVIP

Viruses 2012, 4, 1687-1710; doi:10.3390/v4091687 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Emerging Themes from EBV and KSHV microRNA Targets Dhivya Ramalingam ?, Philippe Kieffer-Kwon ?, and Joseph M. Ziegelbauer * HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; E-Mails: dhivya.ramalingam@ (D.R.); philippe.kieffer-kwon@ (P.K.-K.) ? Both authors contributed equally to this work * Author to whom correspondence should be addressed; E-Mail: ziegelbauerjm@; Tel. +1-301-594-6634. Received: 31 July 2012; in revised form: 22 August 2012 / Accepted: 3 September 2012 / Published: 21 September 2012 Abstract: EBV and KSHV are both gamma-herpesviruses which express multiple viral microRNAs. Various methods have been used to investigate the functions of these microRNAs, largely through identification of microRNA target genes. Surprisingly, these related viruses do not share significant sequence homology in their microRNAs. A number of reports have described functions of EBV and KSHV microRNA targets, however only three experimentally validated target genes have been shown to be targeted by microRNAs from both viruses. More sensitive methods to identify microRNA targets have predicted approximately 60% of host targets could be shared by EBV and KSHV microRNAs, but by targeting different sequences in the host targets. In this review, we explore the similarities of microRNA functions and targets of these related viruses. Keywords: EBV; KSHV; HHV4; HHV8; miRNAs; microRNAs  Viruses 2012, 4 1688 1. Introduction Approximately twenty percent of human cancers are associated with various infectious agents [1]. Two such agents are Epstein-Barr virus (EBV/human herpesvirus 4) and Kaposi’s sarcoma-associated herpesvirus (KSHV/human herpesvirus 8). Other viruses directly linked to human cancers include hepatitis B virus (HBV), hepatitis C