PDF(Pubmed)
Abstract：
Cytokinins (CKs) are a group of N6-substituted signaling molecules whose biosynthesis and metabolism have been documented in all kingdoms of life, including vertebrates. While their biological relevance in vertebrate systems continues to be elucidated, they have broadly been documented with therapeutic effects in exogenous applications. In this study, we evaluated the virostatic potential of four types of CKs including, N6-isopentenyladenine (iP), N6-isopentenyladenosine (iPR), N6-isopentenyladenosine-5\'monophosphate (iPMP), and 2-methylthiol-N6-isopentenyladenosine (2MeSiPR) against the ranavirus type species, frog virus 3 (FV3). Following concurrent treatment and infection, iP and iPR reduced viral replication by 33.8% and 59.6%, respectively, in plaque formation assays. A decrease in viral replication was also observed when CK exposure was limited to 12 h prior to infection, where iP and iPR reduced viral replication by 31% and 23.75%, respectively. Treatment with iP and iPR was also marked by 48% and 60% decreases in viral load over 72 h, respectively, as measured in single step growth curves. Plaque morphology was altered in vitro, as iP and iPR treatment increased plaque area by 83% and 112% with lytic zone formation also becoming more prevalent in corresponding treatments. Treatment with iPMP and 2MeSiPR resulted in no effect on viral kinetics in vitro. The results of this study are the first to provide evidence of CK antiviral activity against a DNA virus and highlight the importance of their structure for therapeutic investigations.
摘要：
细胞分裂素（CKs）是一组N6取代的信号分子，其生物合成和代谢已在所有生命王国中得到证明。包括脊椎动物.虽然它们在脊椎动物系统中的生物学相关性继续得到阐明，它们在外源性应用中具有广泛的治疗效果。在这项研究中,我们评估了四种类型的CKs的病毒抑制电位，包括，N6-异戊烯基腺嘌呤(iP),N6-异戊烯基腺苷(iPR)，N6-异戊烯基腺苷-5'一磷酸（iPMP），和2-甲基硫醇-N6-异戊烯基腺苷（2MeSiPR）对抗ranavirus型物种，青蛙病毒3（FV3）。同时治疗和感染后，iP和iPR使病毒复制减少了33.8%和59.6%，分别,在斑块形成测定中。当CK暴露限于感染前12小时时，也观察到病毒复制减少，其中iP和iPR减少了31%和23.75%的病毒复制，分别。在72小时内，用iP和iPR处理的病毒载量也减少了48％和60％，分别,以单步骤生长曲线测量。斑块形态在体外发生了改变，由于iP和iPR治疗增加了83％和112％的斑块面积，溶解区形成在相应的治疗中也变得更加普遍。用iPMP和2MeSiPR处理对体外病毒动力学没有影响。这项研究的结果是第一个提供针对DNA病毒的CK抗病毒活性的证据，并强调了其结构对治疗研究的重要性。
