MicroRNAs control herpesviral dormancy.

Tumor Virology Program, Greehey Children's Cancer Research Institute, Department of Pediatrics, Microbiology and Immunology, Medicine, and Molecular Medicine, and Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX USA.
Cell cycle (Georgetown, Tex.) (Impact Factor: 5.24). 04/2010; 9(7):1225-6. DOI: 10.4161/cc.9.7.11387
Source: PubMed
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    ABSTRACT: Given the propensity of viruses to co-opt cellular pathways and activities for their benefit, it is perhaps not surprising that several viruses have now been shown to reshape the cellular environment by reprogramming the host's RNA-interference machinery. In particular, microRNAs are produced by the various members of the herpesvirus family during both the latent stage of the viral life cycle and the lytic (or productive) stage. Emerging data suggest that viral microRNAs are particularly important for regulating the transition from latent to lytic replication and for attenuating antiviral immune responses.
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    ABSTRACT: All metazoan eukaryotes express microRNAs (miRNAs), roughly 22-nucleotide regulatory RNAs that can repress the expression of messenger RNAs bearing complementary sequences. Several DNA viruses also express miRNAs in infected cells, suggesting a role in viral replication and pathogenesis. Although specific viral miRNAs have been shown to autoregulate viral mRNAs or downregulate cellular mRNAs, the function of most viral miRNAs remains unknown. Here we report that the miR-K12-11 miRNA encoded by Kaposi's-sarcoma-associated herpes virus (KSHV) shows significant homology to cellular miR-155, including the entire miRNA 'seed' region. Using a range of assays, we show that expression of physiological levels of miR-K12-11 or miR-155 results in the downregulation of an extensive set of common mRNA targets, including genes with known roles in cell growth regulation. Our findings indicate that viral miR-K12-11 functions as an orthologue of cellular miR-155 and probably evolved to exploit a pre-existing gene regulatory pathway in B cells. Moreover, the known aetiological role of miR-155 in B-cell transformation suggests that miR-K12-11 may contribute to the induction of KSHV-positive B-cell tumours in infected patients.
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