This Article Full Text (PDF) Other Versions of this Article: JVI.01521-07v1 81/24/13544    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gandy, S. Z. Articles by Casey, J. L. Search for Related Content PubMed PubMed Citation Articles by Gandy, S. Z. Articles by Casey, J. L.

 Previous Article  |  Next Article 

J. Virol. doi:10.1128/JVI.01521-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

RNA Editing of the HHV-8 Kaposin Transcript Eliminates Its Transforming Activity and Is Induced During Lytic Replication

Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC 20007

^* To whom correspondence should be addressed. Email: caseyj{at}georgetown.edu.

	Abstract

Human herpesvirus 8 (HHV8) is the etiologic agent associated with Kaposi's sarcoma and primary effusion lymphoma (PEL). The K12 RNA, which produces as many as three variants of the kaposin protein, as well as a microRNA, is the most abundant transcript expressed in latent KSHV infection, yet is also induced during lytic replication. The portion of the transcript that includes the microRNA and the kaposin A sequence has been shown to have tumorigenic potential. Genome coordinate 117,990, which is within this transcript, has been found to be heterogeneous - primarily in RNAs, but also among viral DNA sequences. This sequence heterogeneity affects an amino acid in kaposins A and C and the microRNA. The functional effects of this sequence heterogeneity have not been studied, and its origin has not been definitively settled; both RNA editing and heterogeneity at the level of the viral genome have been proposed. Here, we show that transcripts containing A at position 117,990 are tumorigenic, while those with G at this position are not. Using a highly sensitive quantitative assay, we observed that, in PEL cells under conditions where over 60% of cDNAs derived from K12 RNA transcripts have G at 117,990. In contrast, there is no detectable G in the viral DNA sequence at this position, only A. This result is consistent with RNA editing by one of the host RNA adenosine deaminases (ADARs). Indeed, we observed that purified human ADAR1 efficiently edits K12 RNA in vitro. Remarkably, the amount of editing correlated with the replicative state of the virus; editing levels were nearly 10-fold higher in cells treated to induce lytic viral replication. These results suggest that RNA editing controls the function of one segment of the kaposin transcript, such that it has transforming activity during latent replication and possibly another, as yet undetermined, function during lytic replication.