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与单纯疱疹病毒1型立即早期mRNA 4、5和1互补的寡核苷酸甲基膦酸酯的协同抗病毒活性。

Synergistic antiviral activities of oligonucleoside methylphosphonates complementary to herpes simplex virus type 1 immediate-early mRNAs 4, 5, and 1.

作者信息

Kulka M, Smith C C, Levis J, Fishelevich R, Hunter J C, Cushman C D, Miller P S, Ts'o P O, Aurelian L

机构信息

Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201.

出版信息

Antimicrob Agents Chemother. 1994 Apr;38(4):675-80. doi: 10.1128/AAC.38.4.675.

DOI:10.1128/AAC.38.4.675
PMID:8031030
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC284524/
Abstract

An oligonucleoside methylphosphonate (ONMP) complementary to the splice acceptor site of immediate-early (IE) pre-mRNAs 4 and 5 (IE4,5SA) inhibits herpes simplex virus type 1 (HSV-1) growth in vitro and in infected animals. The antiviral effect appears to be due to inhibition of IE pre-mRNA 4 and 5 splicing and/or IE4 gene expression (M. Kulka, M. Wachsman, S. Miura, R. Fishelevich, P. S. Miller, P. O. P. Ts'o, and L. Aurelian, Antiviral Res. 20:115-130, 1993). We describe the potentiation of antiviral activity when we targeted two IE genes with different ONMPs. A psoralen derivative of an ONMP complementary to the IE mRNA 1 (IE1) translation initiation site (IE1TI) covalently bound a 2.8-kb transcript that hybridized with a 20-base oligonucleotide complementary to the 5' leader sequence of IE1 but not a 20-base oligonucleotide complementary to the first intron of IE1. IE1TI inhibited IE1 gene expression and virus replication in cells infected with HSV-1 in vitro. Inhibition was specific because it was not observed with oligomers mutated in two (IE1TImu1) or four (IE1TImu2) central residues or in cells infected with an IE1 deletion mutant (HSV-1 dl1403). IE1TI potentiated the antiviral activity of IE4,5SA (synergistic effect), while potentiation was not observed when IE4,5SA was mixed with IE1TImu1. A similar synergistic effect was seen when IE1TI was mixed with an ONMP complementary to the translation initiation site of IE mRNA 4 but not with an ONMP complementary to the translation initiation site of IE mRNA 5. These findings suggest that synergistic antiviral activity is mediated by targeting at least two IE genes (IE1 and IE4).

摘要

一种与单纯疱疹病毒1型（HSV-1）立即早期（IE）前体mRNA 4和5的剪接受体位点（IE4,5SA）互补的寡核苷酸甲基膦酸酯（ONMP）在体外和感染动物体内均能抑制HSV-1的生长。这种抗病毒作用似乎是由于抑制了IE前体mRNA 4和5的剪接和/或IE4基因的表达（M. Kulka、M. Wachsman、S. Miura、R. Fishelevich、P. S. Miller、P. O. P. Ts'o和L. Aurelian，《抗病毒研究》20:115 - 130，1993）。我们描述了用不同的ONMP靶向两个IE基因时抗病毒活性的增强。一种与IE mRNA 1（IE1）翻译起始位点（IE1TI）互补的ONMP的补骨脂素衍生物共价结合了一个2.8 kb的转录本，该转录本与一个与IE1的5'前导序列互补的20碱基寡核苷酸杂交，但不与与IE1的第一个内含子互补的20碱基寡核苷酸杂交。IE1TI在体外抑制了感染HSV-1的细胞中IE1基因的表达和病毒复制。这种抑制是特异性的，因为在两个（IE1TImu1）或四个（IE1TImu2）中心残基发生突变的寡聚物中未观察到这种抑制，在感染IE1缺失突变体（HSV-1 dl1403）的细胞中也未观察到。IE1TI增强了IE4,5SA的抗病毒活性（协同效应），而当IE4,5SA与IE1TImu1混合时未观察到增强作用。当IE1TI与一个与IE mRNA 4的翻译起始位点互补的ONMP混合时也观察到了类似的协同效应，但与一个与IE mRNA 5的翻译起始位点互补的ONMP混合时未观察到。这些发现表明协同抗病毒活性是通过靶向至少两个IE基因（IE1和IE4）介导的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4741/284524/ed60710dc809/aac00370-0047-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4741/284524/ed60710dc809/aac00370-0047-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4741/284524/ed60710dc809/aac00370-0047-a.jpg

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1
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J Biol Chem. 1954 Jun;208(2):477-88.
2
Processing of the herpes simplex virus regulatory protein alpha 22 mediated by the UL13 protein kinase determines the accumulation of a subset of alpha and gamma mRNAs and proteins in infected cells.由UL13蛋白激酶介导的单纯疱疹病毒调节蛋白α22的加工过程决定了感染细胞中α和γ mRNA及蛋白亚群的积累。
Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6701-5. doi: 10.1073/pnas.90.14.6701.
3
Inhibitors of thymidylate synthase and dihydrofolate reductase potentiate the antiviral effect of acyclovir.
J Virol. 1995 Mar;69(3):1925-31. doi: 10.1128/JVI.69.3.1925-1931.1995.
4
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Antimicrob Agents Chemother. 1995 May;39(5):1157-61. doi: 10.1128/AAC.39.5.1157.
胸苷酸合成酶和二氢叶酸还原酶抑制剂可增强阿昔洛韦的抗病毒作用。
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4
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5
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7
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