Herpes simplex virus type 2 growth and latency reactivation by cocultivation are inhibited with antisense oligonucleotides complementary to the translation initiation site of the large subunit of ribonucleotide reductase (RR1).
Herpes simplex virus type 2 growth and latency reactivation by cocultivation are inhibited with antisense oligonucleotides complementary to the translation initiation site of the large subunit of ribonucleotide reductase (RR1).
复制标题
与核糖核苷酸还原酶 (RR1) 大亚基翻译起始位点互补的反义寡核苷酸可抑制 2 型单纯疱疹病毒的生长和共培养潜伏期再激活。
DOI：
10.1089/oli.1.2000.10.77
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Smith,CC
中科院分区：
文献类型：
--
作者：
Aurelian,L;Smith,CC
Antisense oligonucleotides complementary to the translation initiation site of the herpes simplex virus type 2 (HSV-2) large subunit of ribonucleotide reductase (RR1) were studied for their ability to inhibit RR1 expression, HSV-2 growth, and its reactivation from latently infected ganglia. The oligomers caused a significant decrease (90%–97% inhibition) in HSV-2 RR1 expression and inhibited HSV-2 growth, with IC50and IC90values of 0.11 and 1.0 μM, respectively. The titers of HSV-2 mutants that are respectively deleted in the PK (ICP10ΔPK) or RR (ICP10ΔRR) domains of RR1 were also significantly (500–20,000-fold) decreased, indicating that the antisense oligomers interfere with the independent contributions of the two RR1 functions (PK and RR) toward virus growth. Inhibition was sequence specific, as evidenced by the failure of a two-base mutant (RRlTImu) to inhibit protein expression and HSV-2 growth. Furthermore, the antisense oligomers inhibited HSV-2 reactivation by cocultivation of latently infected ganglia (0/8). Virus was reactivated from ganglia cultured without oligomers, in the presence of unrelated oligomers (6/8), or in the presence of the two-base mutant RR1TImu(5/8) (p< 0.007 by two-tailed Fisher exact test). HSV-2 growth was not inhibited by antisense oligonucleotides complementary to the splice junction of HSV-2 immediate-early (IE) pre-mRNA 4 and 5 (IE4,5SA) or the translation initiation site of IE mRNA 4 (IE4TI), although the respective HSV-1-specific oligomers inhibit HSV-1 growth.
