RNA editing of the human herpesvirus 8 kaposin transcript eliminates its transforming activity and is induced during lytic replication.
J Virol
; 81(24): 13544-51, 2007 Dec.
Article
em En
| MEDLINE
| ID: mdl-17913828
ABSTRACT
Human herpesvirus 8 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 Kaposi's sarcoma-associated herpesvirus infection, and yet it 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 117990, 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 117990 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 more than 60% of cDNAs derived from K12 RNA transcripts have G at coordinate 117990, 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.
Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Proteínas Virais
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Replicação Viral
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Regulação Viral da Expressão Gênica
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Transformação Celular Viral
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Edição de RNA
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Herpesvirus Humano 8
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Virol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos