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Published on: April 17, 2017
Hepatitis C virus genomic RNA dimerization is mediated via a kissing complex intermediate
Sumangala Shetty1, Seungtaek Kim, Tetsuro Shimakami
1Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, Pennsylvania 15282, USA.
RNA (New York, N.Y.)
|April 3, 2010
Summary
Hepatitis C virus (HCV) genomic RNA dimerization is mediated by a conserved X55 region through a kissing complex intermediate. Core protein stabilizes this complex, impacting viral replication and infectious virus production.
Area of Science:
- Virology
- Molecular Biology
- RNA Biology
Background:
- Hepatitis C virus (HCV) infects over 200 million people globally, necessitating improved therapies.
- HCV's high mutation rate stems from its error-prone RNA polymerase.
- A highly conserved 55-nucleotide (nt) sequence (X55 RNA) in the 3'-untranslated region is crucial for viral RNA structure.
Purpose of the Study:
- To elucidate the mechanism of HCV genomic RNA dimerization.
- To characterize the role of the conserved X55 RNA region in this process.
Main Methods:
- Analysis of the X55 RNA region.
- Investigating RNA dimerization using in vitro assays.
- Assessing the impact of mutations on viral replication in transfected cells.
Main Results:
- HCV RNA dimerization involves a kissing complex intermediate, similar to HIV-1.
- The viral core protein stabilizes the dimer into an extended duplex conformation.
- Mutations disrupting dimerization reduced, but did not eliminate, viral RNA replication and infectious virus production.
Conclusions:
- The X55 RNA region is essential for HCV RNA dimerization.
- Core protein-mediated stabilization of the dimer is critical for viral propagation.
- Targeting RNA dimerization could be a potential therapeutic strategy for HCV.
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