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PMID: 2550925 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Site specificity of the inhibitory effects of oligo(nucleoside methylphosphonate)s complementary to the acceptor splice junction of herpes simplex virus type 1 immediate early mRNA 4.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 86 ·No. 18 ·1989-09-00 ·Pages 6868-72

Kulka M, Smith CC, Aurelian L, Fishelevich R, Meade K, Miller P, Ts'o PO

Abstract

Oligo(nucleoside methylphosphonate)s complementary to the splice junction of herpes simplex virus type 1 immediate early pre-mRNAs 4 and 5 caused specific inhibition of herpes simplex virus type 1 growth. The dodecamer d(TpTCCTCCTGCGG) (deoxynucleoside methylphosphonate residues in italic) caused 50% and 98% decreases in herpes simplex virus type 1 titers at concentrations of 15 microM and 100 microM, respectively. d(TpTCCTCCTGCGG) inhibited viral but not cellular protein synthesis and decreased splicing of immediate early pre-mRNAs 4 and 5. Inhibition was highly sequence specific. A psoralen derivative of d(TpTCCTCCTGCGG) that can covalently bind to complementary sequences after exposure to 365-nm irradiation caused 90-98% inhibition of virus growth in cells treated with oligomer (5 microM) and irradiated at 1-3 hr postinfection. The data suggest that oligo(nucleoside methylphosphonate)s of appropriate sequence and derivatization may be effective as antiviral agents.

MeSH Terms
Animals Base Sequence Cell Line Exons Genes, Viral Introns Molecular Sequence Data Oligonucleotides/pharmacology Organophosphonates/pharmacology Protein Biosynthesis RNA Splicing/drug effects RNA, Messenger/drug effects,genetics RNA, Viral/drug effects,genetics Simplexvirus/drug effects,genetics,growth & development Ultraviolet Rays Vero Cells
Chemicals
Oligonucleotides Organophosphonates RNA, Messenger RNA, Viral
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kulka M
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201.
Smith C C
Aurelian L
Fishelevich R
Meade K
Miller P
Ts'o P O
References (30)
30 references, click to expand
  1. Regulation of herpesvirus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins.
    J Virol. 1974 Jul;14(1):8-19 PMID: 4365321
  2. Photochemical cross-linking of psoralen-derivatized oligonucleoside methylphosphonates to rabbit globin messenger RNA.
    Biochemistry. 1988 Dec 27;27(26):9113-21 PMID: 2468360
  3. Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide.
    Proc Natl Acad Sci U S A. 1978 Jan;75(1):280-4 PMID: 75545
  4. Incomplete splicing and deficient accumulation of the fiber messenger RNA in monkey cells infected by human adenovirus type 2.
    J Mol Biol. 1980 May 15;139(2):221-42 PMID: 7411632
  5. Biochemical and biological effects of nonionic nucleic acid methylphosphonates.
    Biochemistry. 1981 Mar 31;20(7):1874-80 PMID: 7013804
  6. DNA sequence of an immediate-early gene (IEmRNA-5) of herpes simplex virus type I.
    Nucleic Acids Res. 1982 Feb 11;10(3):979-91 PMID: 6278443
  7. Detailed structural analysis of two spliced HSV-1 immediate-early mRNAs.
    Nucleic Acids Res. 1982 Apr 10;10(7):2241-56 PMID: 6283473
  8. The junctions between the repetitive and the short unique sequences of the herpes simplex virus genome are determined by the polypeptide-coding regions of two spliced immediate-early mRNAs.
    J Gen Virol. 1984 Mar;65 ( Pt 3):451-66 PMID: 6321634
  9. Inhibition of thymidine kinase gene expression by anti-sense RNA: a molecular approach to genetic analysis.
    Cell. 1984 Apr;36(4):1007-15 PMID: 6323013
  10. Expression of immediate-early genes in herpes simplex virus type 1-infected XC cells: lack of ICP22 (68K) polypeptide.
    J Gen Virol. 1984 Aug;65 ( Pt 8):1331-40 PMID: 6086819
  11. In vitro transcription of herpes simplex virus genes: identification of a new initiation site and second intervening sequence in the immediate-early RNA-5 gene.
    J Virol. 1985 Jan;53(1):235-42 PMID: 2981342
  12. Injected anti-sense RNAs specifically block messenger RNA translation in vivo.
    Proc Natl Acad Sci U S A. 1985 Jan;82(1):144-8 PMID: 3855537
  13. Herpes simplex virus 1 mutant deleted in the alpha 22 gene: growth and gene expression in permissive and restrictive cells and establishment of latency in mice.
    J Virol. 1985 Aug;55(2):338-46 PMID: 2991560
  14. Hybridization arrest of globin synthesis in rabbit reticulocyte lysates and cells by oligodeoxyribonucleoside methylphosphonates.
    Biochemistry. 1985 Oct 22;24(22):6139-45 PMID: 4084511
  15. 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.
    Proc Natl Acad Sci U S A. 1986 May;83(9):2787-91 PMID: 3010316
  16. Solid-phase syntheses of oligodeoxyribonucleoside methylphosphonates.
    Biochemistry. 1986 Sep 9;25(18):5092-7 PMID: 3768335
  17. Construction and properties of a viable herpes simplex virus 1 recombinant lacking coding sequences of the alpha 47 gene.
    J Virol. 1986 Nov;60(2):807-12 PMID: 3022015
  18. Inhibition of vesicular stomatitis virus protein synthesis and infection by sequence-specific oligodeoxyribonucleoside methylphosphonates.
    Biochemistry. 1986 Oct 7;25(20):6268-75 PMID: 3024704
  19. Antisense RNA injections in fertilized frog eggs reveal an RNA duplex unwinding activity.
    Cell. 1987 Feb 27;48(4):599-605 PMID: 2434240
  20. Antisense RNA of proto-oncogene c-fos blocks renewed growth of quiescent 3T3 cells.
    Mol Cell Biol. 1987 Feb;7(2):639-49 PMID: 3547078
  21. The regulation of transcription of viral and cellular genes by herpesvirus immediate-early gene products (review).
    Anticancer Res. 1987 Jul-Aug;7(4A):589-604 PMID: 3310848
  22. Phosphorothioate analogs of oligodeoxynucleotides: inhibitors of replication and cytopathic effects of human immunodeficiency virus.
    Proc Natl Acad Sci U S A. 1987 Nov;84(21):7706-10 PMID: 3499613
  23. Selective inhibition of the cytopathic effect of type A influenza viruses by oligodeoxynucleotides covalently linked to an intercalating agent.
    Nucleic Acids Res. 1987 Dec 10;15(23):9909-19 PMID: 3697085
  24. Antisense RNA inhibits endogenous gene expression in mouse preimplantation embryos: lack of double-stranded RNA "melting" activity.
    Proc Natl Acad Sci U S A. 1988 Feb;85(3):831-5 PMID: 2448782
  25. Human promyelocytic leukemia HL-60 cell proliferation and c-myc protein expression are inhibited by an antisense pentadecadeoxynucleotide targeted against c-myc mRNA.
    Proc Natl Acad Sci U S A. 1988 Feb;85(4):1028-32 PMID: 3277186
  26. Interaction of origin binding protein with an origin of replication of herpes simplex virus 1.
    Proc Natl Acad Sci U S A. 1988 May;85(9):2959-63 PMID: 2834723
  27. Interaction of psoralen-derivatized oligodeoxyribonucleoside methylphosphonates with single-stranded DNA.
    Biochemistry. 1988 May 3;27(9):3197-203 PMID: 3390429
  28. Inhibition of human immunodeficiency virus replication by antisense oligodeoxynucleotides.
    Proc Natl Acad Sci U S A. 1988 Aug;85(15):5507-11 PMID: 3041414
  29. Inhibition of human immunodeficiency virus by using an oligonucleoside methylphosphonate targeted to the tat-3 gene.
    J Virol. 1988 Oct;62(10):3914-7 PMID: 2458490
  30. Regulation of herpesvirus macromolecular synthesis. V. Properties of alpha polypeptides made in HSV-1 and HSV-2 infected cells.
    Virology. 1977 Apr;77(2):733-49 PMID: 193259
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.86.18.6868
Published
1989-09-00
Pages
6868-72
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC297951
Subset
IM
Grants
NCI NIH HHS · CA 42762 · United States
NIGMS NIH HHS · GM 31927 · United States
External Links
PubMed source DOI: 10.1073/pnas.86.18.6868 PMC Full Text View journal details
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