Suppressing Kaposi's Sarcoma-Associated Herpesvirus Lytic Gene Expression and Replication by RNase P Ribozyme

Kaposi's sarcoma, an AIDS-defining illness, is caused by Kaposi's sarcoma-associated herpesvirus (KSHV), an oncogenic virus. In this study, we engineered ribozymes derived from ribonuclease P (RNase P) catalytic RNA with targeting against the mRNA encoding KSHV immediate early replication...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2023-04, Vol.28 (8), p.3619
Main Authors: Liu, Yujun, Chen, Yuan-Chuan, Yan, Bin, Liu, Fenyong
Format: Article
Language:English
Subjects:
antiviral
Care and treatment
Catalytic RNA
Cloning
Enzymes
Gene Expression
Gene Expression Regulation, Viral
gene therapy
Genetic aspects
Health aspects
Herpes viruses
herpesvirus
Herpesvirus 8, Human - genetics
Herpesvirus 8, Human - metabolism
Herpesviruses
Immediate-Early Proteins - metabolism
Infections
Kaposi sarcoma-associated herpesvirus
Kaposi's sarcoma
Kaposis sarcoma
Kinases
Mutation
Proteins
Replication
Ribonuclease P
Ribonuclease P - genetics
Ribonuclease P - metabolism
ribozyme
Ribozymes
RNA, Catalytic - genetics
RNA, Catalytic - metabolism
RNA, Messenger - genetics
RNase P
Sarcoma
Trans-Activators - genetics
Transfer RNA
Viral infections
Virus Latency
Virus Replication - genetics
Viruses
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Description
Summary:Kaposi's sarcoma, an AIDS-defining illness, is caused by Kaposi's sarcoma-associated herpesvirus (KSHV), an oncogenic virus. In this study, we engineered ribozymes derived from ribonuclease P (RNase P) catalytic RNA with targeting against the mRNA encoding KSHV immediate early replication and transcription activator (RTA), which is vital for KSHV gene expression. The functional ribozyme F-RTA efficiently sliced the RTA mRNA sequence in vitro. In cells, KSHV production was suppressed with ribozyme F-RTA expression by 250-fold, and RTA expression was suppressed by 92-94%. In contrast, expression of control ribozymes hardly affected RTA expression or viral production. Further studies revealed both overall KSHV early and late gene expression and viral growth decreased because of F-RTA-facilitated suppression of RTA expression. Our results indicate the first instance of RNase P ribozymes having potential for use in anti-KSHV therapy.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules28083619