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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/8/3619 |
| _version_ | 1797604097991376896 |
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| author | Yujun Liu Yuan-Chuan Chen Bin Yan Fenyong Liu |
| author_facet | Yujun Liu Yuan-Chuan Chen Bin Yan Fenyong Liu |
| author_sort | Yujun Liu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T04:41:30Z |
| format | Article |
| id | doaj.art-6ae5b7db7dc84c65b66c51d4a75cf1a2 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T04:41:30Z |
| publishDate | 2023-04-01 |
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| series | Molecules |
| spelling | doaj.art-6ae5b7db7dc84c65b66c51d4a75cf1a22023-11-17T20:41:35ZengMDPI AGMolecules1420-30492023-04-01288361910.3390/molecules28083619Suppressing Kaposi’s Sarcoma-Associated Herpesvirus Lytic Gene Expression and Replication by RNase P RibozymeYujun Liu0Yuan-Chuan Chen1Bin Yan2Fenyong Liu3School of Public Health, University of California, Berkeley, CA 94720, USAProgram in Comparative Biochemistry, University of California, Berkeley, CA 94720, USASchool of Public Health, University of California, Berkeley, CA 94720, USASchool of Public Health, University of California, Berkeley, CA 94720, USAKaposi’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.https://www.mdpi.com/1420-3049/28/8/3619Kaposi sarcoma-associated herpesvirusherpesvirusantiviralgene therapyRNase Pribozyme |
| spellingShingle | Yujun Liu Yuan-Chuan Chen Bin Yan Fenyong Liu Suppressing Kaposi’s Sarcoma-Associated Herpesvirus Lytic Gene Expression and Replication by RNase P Ribozyme Molecules Kaposi sarcoma-associated herpesvirus herpesvirus antiviral gene therapy 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 | Kaposi sarcoma-associated herpesvirus herpesvirus antiviral gene therapy RNase P ribozyme |
| url | https://www.mdpi.com/1420-3049/28/8/3619 |
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