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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 and transc...

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Detalles Bibliográficos
Autores principales: Liu, Yujun, Chen, Yuan-Chuan, Yan, Bin, Liu, Fenyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10142857/
https://www.ncbi.nlm.nih.gov/pubmed/37110852
http://dx.doi.org/10.3390/molecules28083619
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author Liu, Yujun
Chen, Yuan-Chuan
Yan, Bin
Liu, Fenyong
author_facet Liu, Yujun
Chen, Yuan-Chuan
Yan, Bin
Liu, Fenyong
author_sort Liu, Yujun
collection PubMed
description 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.
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spelling pubmed-101428572023-04-29 Suppressing Kaposi’s Sarcoma-Associated Herpesvirus Lytic Gene Expression and Replication by RNase P Ribozyme Liu, Yujun Chen, Yuan-Chuan Yan, Bin Liu, Fenyong Molecules Article 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. MDPI 2023-04-21 /pmc/articles/PMC10142857/ /pubmed/37110852 http://dx.doi.org/10.3390/molecules28083619 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Yujun
Chen, Yuan-Chuan
Yan, Bin
Liu, Fenyong
Suppressing Kaposi’s Sarcoma-Associated Herpesvirus Lytic Gene Expression and Replication by RNase P Ribozyme
title Suppressing Kaposi’s Sarcoma-Associated Herpesvirus Lytic Gene Expression and Replication by RNase P Ribozyme
title_full Suppressing Kaposi’s Sarcoma-Associated Herpesvirus Lytic Gene Expression and Replication by RNase P Ribozyme
title_fullStr Suppressing Kaposi’s Sarcoma-Associated Herpesvirus Lytic Gene Expression and Replication by RNase P Ribozyme
title_full_unstemmed Suppressing Kaposi’s Sarcoma-Associated Herpesvirus Lytic Gene Expression and Replication by RNase P Ribozyme
title_short Suppressing Kaposi’s Sarcoma-Associated Herpesvirus Lytic Gene Expression and Replication by RNase P Ribozyme
title_sort suppressing kaposi’s sarcoma-associated herpesvirus lytic gene expression and replication by rnase p ribozyme
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10142857/
https://www.ncbi.nlm.nih.gov/pubmed/37110852
http://dx.doi.org/10.3390/molecules28083619
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