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Updated: May 10, 2026

MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
Selective degradation of host MicroRNAs by an intergenic HCMV noncoding RNA accelerates virus production
Sanghyun Lee1, Jaewon Song, Sungchul Kim
1National Creative Research Initiatives Center for Antigen Presentation, Seoul 151-747, Republic of Korea.
Abstract:
Virulence of human cytomegalovirus (HCMV) clinical isolates correlates with carriage of a 15 kb segment in the UL/b' region of the viral genome, which is absent from attenuated strains. The mechanisms by which this segment contributes to HCMV virulence remain obscure. We observed that intergenic RNA sequences within the 15 kb segment function as a microRNA (miRNA) decay element (miRDE) and direct the selective, sequence-specific turnover of mature miR-17 and miR-20a encoded within the host miR-17-92 cluster. Unlike canonical miRNA-mRNA interactions, the miRNA-miRDE interactions did not repress miRDE expression. miRNA binding site mutations retargeted miRDE to other miR-17-92 cluster miRNAs, which are otherwise resistant to miRDE-mediated decay. miRDE function was required to accelerate virus production in the context of lytic HCMV infection. These results indicate a role for viral noncoding RNA in regulating cellular miRNAs during HCMV pathogenesis and suggest that noncoding RNAs may play a role in mature miRNA turnover.
Insights
Human cytomegalovirus (HCMV) uses a viral RNA element to degrade specific host microRNAs (miRNAs), enhancing viral replication. This discovery reveals a novel mechanism of viral pathogenesis involving noncoding RNA regulation.
Area of Science:
- Virology
- Molecular Biology
- RNA Biology
Background:
- Human cytomegalovirus (HCMV) virulence is linked to a specific genomic segment.
- The mechanism by which this segment influences virulence is not well understood.
Purpose of the Study:
- To investigate the function of a 15 kb segment in HCMV virulence.
- To elucidate the role of viral noncoding RNA in regulating host microRNAs.
Main Methods:
- Analysis of intergenic RNA sequences within the HCMV 15 kb segment.
- Investigating the interaction between viral RNA and host microRNAs (miRNAs).
- Assessing the impact of these interactions on viral production during lytic infection.
Main Results:
- Viral RNA sequences function as miRNA decay elements (miRDEs), selectively degrading mature miR-17 and miR-20a.
- Mutations in miRNA binding sites altered miRDE targeting to other cluster miRNAs.
- miRDE activity was essential for accelerated virus production in lytic HCMV infection.
Conclusions:
- Viral noncoding RNA regulates cellular miRNAs during HCMV infection.
- Noncoding RNAs may play a significant role in the turnover of mature miRNAs.
- This interaction contributes to HCMV pathogenesis and virulence.
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