
Inhibition of herpes simplex virus 1 gene expression and replication by RNase P-associated external guide sequences
Author(s) -
Jin Liu,
Luyao Shao,
Phong Trang,
Yan Zhu,
Michael A. Reeves,
Xu Sun,
Gia-Phong Vu,
Yu Wang,
Hongjian Li,
Chengchao Zheng,
Sangwei Lu,
Fenyong Liu
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep27068
Subject(s) - rnase p , biology , gene , messenger rna , gene expression , herpes simplex virus , rna , transfer rna , microbiology and biotechnology , viral replication , transcription (linguistics) , ribonuclease iii , ribonuclease , virus , virology , genetics , rna interference , linguistics , philosophy
An external guide sequence (EGS) is a RNA sequence which can interact with a target mRNA to form a tertiary structure like a pre-tRNA and recruit intracellular ribonuclease P (RNase P), a tRNA processing enzyme, to degrade target mRNA. Previously, an in vitro selection procedure has been used by us to engineer new EGSs that are more robust in inducing human RNase P to cleave their targeted mRNAs. In this study, we constructed EGSs from a variant to target the mRNA encoding herpes simplex virus 1 (HSV-1) major transcription regulator ICP4, which is essential for the expression of viral early and late genes and viral growth. The EGS variant induced human RNase P cleavage of ICP4 mRNA sequence 60 times better than the EGS generated from a natural pre-tRNA. A decrease of about 97% and 75% in the level of ICP4 gene expression and an inhibition of about 7,000- and 500-fold in viral growth were observed in HSV infected cells expressing the variant and the pre-tRNA-derived EGS, respectively. This study shows that engineered EGSs can inhibit HSV-1 gene expression and viral growth. Furthermore, these results demonstrate the potential for engineered EGS RNAs to be developed and used as anti-HSV therapeutics.