School of Public Health, University of California, Berkeley, CA 94720, USA.
Program in Comparative Biochemistry, University of California, Berkeley, CA 94720, USA.
Molecules. 2023 Apr 21;28(8):3619. doi: 10.3390/molecules28083619.
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.
卡波氏肉瘤，一种艾滋病定义性疾病，是由卡波氏肉瘤相关疱疹病毒（KSHV）引起的，该病毒是一种致癌病毒。在这项研究中，我们设计了源自核糖核酸酶 P（RNase P）催化 RNA 的核酶，针对编码 KSHV 早期复制和转录激活剂（RTA）的 mRNA，该激活剂对于 KSHV 基因表达至关重要。功能核酶 F-RTA 可有效地在体外切割 RTA mRNA 序列。在细胞中，通过表达核酶 F-RTA 将 KSHV 的产生抑制了 250 倍，并且 RTA 的表达抑制了 92-94％。相比之下，对照核酶的表达几乎没有影响 RTA 的表达或病毒的产生。进一步的研究表明，由于 F-RTA 促进了 RTA 表达的抑制，因此总体上 KSHV 的早期和晚期基因表达以及病毒的生长均降低了。我们的研究结果表明，RNase P 核酶首次具有用于抗 KSHV 治疗的潜力。
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