Antiviral effect of an oligo(nucleoside methylphosphonate) complementary to the splice junction of herpes simplex virus type 1 immediate early pre-mRNAs 4 and 5.
Antiviral effect of an oligo(nucleoside methylphosphonate) complementary to the splice junction of herpes simplex virus type 1 immediate early pre-mRNAs 4 and 5.
复制标题
与 1 型单纯疱疹病毒立即早期前 mRNA 4 和 5 的剪接点互补的寡核苷酸（甲基膦酸核苷）的抗病毒作用。
DOI：
10.1073/pnas.83.9.2787
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发表时间：
1986
影响因子：
11.1
通讯作者：
Ts'o,PO
中科院分区：
文献类型：
--
作者：
Smith,CC;Aurelian,L;Reddy,MP;Miller,PS;Ts'o,PO
选择性抑制单纯疱疹病毒1型(HSV-1)的即刻早期(IE)基因可抑制病毒的生长。HSV-1感染细胞在感染前(1-24小时)或感染时用与HSV-1 IE Pre-mRNA4和5的受体剪接连接互补的寡核苷酸(TpCCTCCTG)处理HSV-1感染细胞，可引起剂量依赖的病毒复制抑制。在25微米和75微米低聚物处理的细胞中，病毒滴度分别下降了50%和90%；在300微米时，观察到病毒产量下降了99%。病毒DNA合成减少70%-75%，病毒蛋白合成减少90%，包括其他IE物种和病毒功能蛋白(主要DNA结合130 kDa)和结构蛋白(糖蛋白GB)。在相同的浓度范围内，d(TpCCTCCTG)对未感染细胞的蛋白质合成和生长率的影响很小(0-30%)，低于40%。提示低聚核苷甲基膦酸酯S在抗病毒化疗中可能具有一定的疗效。
Selective inhibition of regulatory immediate early (IE) genes of herpes simplex virus type 1 (HSV-1) should inhibit virus growth. Treatment of HSV-1-infected cells with the oligo(nucleoside methylphosphonate) d(TpCCTCCTG) (deoxynucleoside methylphosphonate residues in italic), which is complementary to the acceptor splice junction of HSV-1 IE pre-mRNA 4 and 5, before (1-24 hr) or at the time of infection caused a dose-dependent inhibition in virus replication. Virus titers were decreased 50% and 90% in cells treated with 25 microM and 75 microM oligomer, respectively; at 300 microM, a 99% reduction in virus production was observed. Viral DNA synthesis was reduced 70-75% and there was a 90% reduction in synthesis of viral proteins, including other IE species and viral functional (130-kDa major DNA-binding) and structural (glycoprotein gB) proteins. In the same concentration range, d(TpCCTCCTG) caused a minimal reduction (0-30%) in protein synthesis and growth rates (less than 40%) of uninfected cells. The data suggest that oligo(nucleoside methylphosphonate)s may be effective in antiviral chemotherapy.