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- Title
RNase P Ribozymes Inhibit the Replication of Human Cytomegalovirus by Targeting Essential Viral Capsid Proteins.
- Authors
Zhu Yang; Yu Wang; Trang, Phong; Jingxue Sheng; Fenyong Liu; Li Zhu; Jun Ye; Jianguo Wu; Ke Zen; Reeves, Michael
- Abstract
An engineered RNase P-based ribozyme variant, which was generated using the in vitro selection procedure, was used to target the overlapping mRNA region of two proteins essential for human cytomegalovirus (HCMV) replication: capsid assembly protein (AP) and protease (PR). In vitro studies showed that the generated variant, V718-A, cleaved the target AP mRNA sequence efficiently and its activity was about 60-fold higher than that of wild type ribozyme M1-A. Furthermore, we observed a reduction of 98%-99% in AP/PR expression and an inhibition of 50,000 fold in viral growth in cells with V718-A, while a 75% reduction in AP/PR expression and a 500-fold inhibition in viral growth was found in cells with M1-A. Examination of the antiviral effects of the generated ribozyme on the HCMV replication cycle suggested that viral DNA encapsidation was inhibited and as a consequence, viral capsid assembly was blocked when the expression of AP and PR was inhibited by the ribozyme. Thus, our study indicates that the generated ribozyme variant is highly effective in inhibiting HCMV gene expression and blocking viral replication, and suggests that engineered RNase P ribozyme can be potentially developed as a promising gene-targeting agent for anti-HCMV therapy.
- Subjects
RIBONUCLEASE P; CATALYTIC RNA; HUMAN cytomegalovirus; CAPSIDS; PROTEOLYTIC enzymes; MESSENGER RNA
- Publication
Viruses (1999-4915), 2015, Vol 7, Issue 7, p3345
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v7072775