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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10142857 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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