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. 1991 Aug 25;19(16):4459–4465. doi: 10.1093/nar/19.16.4459

Analysis of herpes simplex virus-induced mRNA destabilizing activity using an in vitro mRNA decay system.

C M Sorenson 1, P A Hart 1, J Ross 1
PMCID: PMC328634  PMID: 1653415

Abstract

Most host mRNAs are degraded soon after infection of cells with herpes simplex virus type 1 (HSV-1). This early shutoff or early destabilization response is induced by a virion component, the virion host shutoff (vhs) protein. HSV-1 mutants, vhs1 and vhs-delta Sma, which produce defective or inactive vhs protein, fail to induce early shutoff. We have used an in vitro mRNA decay system to analyze the destabilization process. Polysomes from uninfected human erythroleukemia cells, used as a source of target mRNAs, were mixed with polysomes or with post-polysomal supernatant (S130) from HSV-1- or mock-infected murine erythroleukemia cells. Normally stable gamma-globin mRNA was destabilized by approximately 15-fold with S130 from wild-type virus-infected cells but was not destabilized with S130 from mock-infected cells or from cells infected with either of the two HSV mutants. The virus-induced destabilizing activity had no significant effect on the in vitro half-lives of two normally unstable mRNAs, histone and c-myc. No destabilizing activity was detected in polysomes from infected cells. We conclude that a virus-induced destabilizer activity can function in vitro, is located in the S130 of infected cells, and accelerates the decay rates of some, but not all, polysome-associated host mRNAs.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baglioni C., De Benedetti A., Williams G. J. Cleavage of nascent reovirus mRNA by localized activation of the 2'-5'-oligoadenylate-dependent endoribonuclease. J Virol. 1984 Dec;52(3):865–871. doi: 10.1128/jvi.52.3.865-871.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bandziulis R. J., Swanson M. S., Dreyfuss G. RNA-binding proteins as developmental regulators. Genes Dev. 1989 Apr;3(4):431–437. doi: 10.1101/gad.3.4.431. [DOI] [PubMed] [Google Scholar]
  3. Blackburn P., Wilson G., Moore S. Ribonuclease inhibitor from human placenta. Purification and properties. J Biol Chem. 1977 Aug 25;252(16):5904–5910. [PubMed] [Google Scholar]
  4. Brawerman G. mRNA decay: finding the right targets. Cell. 1989 Apr 7;57(1):9–10. doi: 10.1016/0092-8674(89)90166-9. [DOI] [PubMed] [Google Scholar]
  5. Brewer G., Ross J. Poly(A) shortening and degradation of the 3' A+U-rich sequences of human c-myc mRNA in a cell-free system. Mol Cell Biol. 1988 Apr;8(4):1697–1708. doi: 10.1128/mcb.8.4.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carneiro M., Schibler U. Accumulation of rare and moderately abundant mRNAs in mouse L-cells is mainly post-transcriptionally regulated. J Mol Biol. 1984 Oct 5;178(4):869–880. doi: 10.1016/0022-2836(84)90316-4. [DOI] [PubMed] [Google Scholar]
  7. Cleveland D. W., Yen T. J. Multiple determinants of eukaryotic mRNA stability. New Biol. 1989 Nov;1(2):121–126. [PubMed] [Google Scholar]
  8. Dani C., Piechaczyk M., Audigier Y., El Sabouty S., Cathala G., Marty L., Fort P., Blanchard J. M., Jeanteur P. Characterization of the transcription products of glyceraldehyde 3-phosphate-dehydrogenase gene in HeLa cells. Eur J Biochem. 1984 Dec 3;145(2):299–304. doi: 10.1111/j.1432-1033.1984.tb08552.x. [DOI] [PubMed] [Google Scholar]
  9. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dixon R. A., Schaffer P. A. Fine-structure mapping and functional analysis of temperature-sensitive mutants in the gene encoding the herpes simplex virus type 1 immediate early protein VP175. J Virol. 1980 Oct;36(1):189–203. doi: 10.1128/jvi.36.1.189-203.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Everett R. D., Fenwick M. L. Comparative DNA sequence analysis of the host shutoff genes of different strains of herpes simplex virus: type 2 strain HG52 encodes a truncated UL41 product. J Gen Virol. 1990 Jun;71(Pt 6):1387–1390. doi: 10.1099/0022-1317-71-6-1387. [DOI] [PubMed] [Google Scholar]
  12. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  13. Fenwick M. L., Clark J. Early and delayed shut-off of host protein synthesis in cells infected with herpes simplex virus. J Gen Virol. 1982 Jul;61(Pt 50):121–125. doi: 10.1099/0022-1317-61-1-121. [DOI] [PubMed] [Google Scholar]
  14. Fenwick M. L., Everett R. D. Inactivation of the shutoff gene (UL41) of herpes simplex virus types 1 and 2. J Gen Virol. 1990 Dec;71(Pt 12):2961–2967. doi: 10.1099/0022-1317-71-12-2961. [DOI] [PubMed] [Google Scholar]
  15. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Grange T., de Sa C. M., Oddos J., Pictet R. Human mRNA polyadenylate binding protein: evolutionary conservation of a nucleic acid binding motif. Nucleic Acids Res. 1987 Jun 25;15(12):4771–4787. doi: 10.1093/nar/15.12.4771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Heintz N., Zernik M., Roeder R. G. The structure of the human histone genes: clustered but not tandemly repeated. Cell. 1981 Jun;24(3):661–668. doi: 10.1016/0092-8674(81)90092-1. [DOI] [PubMed] [Google Scholar]
  18. Herz C., Stavnezer E., Krug R., Gurney T., Jr Influenza virus, an RNA virus, synthesizes its messenger RNA in the nucleus of infected cells. Cell. 1981 Nov;26(3 Pt 1):391–400. doi: 10.1016/0092-8674(81)90208-7. [DOI] [PubMed] [Google Scholar]
  19. Hill T. M., Sadler J. R., Betz J. L. Virion component of herpes simplex virus type 1 KOS interferes with early shutoff of host protein synthesis induced by herpes simplex virus type 2 186. J Virol. 1985 Oct;56(1):312–316. doi: 10.1128/jvi.56.1.312-316.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Inglis S. C. Inhibition of host protein synthesis and degradation of cellular mRNAs during infection by influenza and herpes simplex virus. Mol Cell Biol. 1982 Dec;2(12):1644–1648. doi: 10.1128/mcb.2.12.1644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Krikorian C. R., Read G. S. In vitro mRNA degradation system to study the virion host shutoff function of herpes simplex virus. J Virol. 1991 Jan;65(1):112–122. doi: 10.1128/jvi.65.1.112-122.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kwong A. D., Frenkel N. Herpes simplex virus-infected cells contain a function(s) that destabilizes both host and viral mRNAs. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1926–1930. doi: 10.1073/pnas.84.7.1926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kwong A. D., Frenkel N. The herpes simplex virus virion host shutoff function. J Virol. 1989 Nov;63(11):4834–4839. doi: 10.1128/jvi.63.11.4834-4839.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kwong A. D., Kruper J. A., Frenkel N. Herpes simplex virus virion host shutoff function. J Virol. 1988 Mar;62(3):912–921. doi: 10.1128/jvi.62.3.912-921.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lazaridis I., Babich A., Nevins J. R. Role of the adenovirus 72-kDa DNA binding protein in the rapid decay of early viral mRNA. Virology. 1988 Aug;165(2):438–445. doi: 10.1016/0042-6822(88)90587-9. [DOI] [PubMed] [Google Scholar]
  26. London F. S., Brinker J. M., Ziaie Z., Kefalides N. A. Suppression of host mRNA in human smooth muscle cells by a virion competent factor in herpes simplex virus type 1. Lab Invest. 1990 Feb;62(2):189–195. [PubMed] [Google Scholar]
  27. Mayman B. A., Nishioka Y. Differential stability of host mRNAs in Friend erythroleukemia cells infected with herpes simplex virus type 1. J Virol. 1985 Jan;53(1):1–6. doi: 10.1128/jvi.53.1.1-6.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. McGeoch D. J., Dalrymple M. A., Davison A. J., Dolan A., Frame M. C., McNab D., Perry L. J., Scott J. E., Taylor P. The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol. 1988 Jul;69(Pt 7):1531–1574. doi: 10.1099/0022-1317-69-7-1531. [DOI] [PubMed] [Google Scholar]
  29. Nishioka Y., Silverstein S. Degradation of cellular mRNA during infection by herpes simplex virus. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2370–2374. doi: 10.1073/pnas.74.6.2370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Nishioka Y., Silverstein S. Requirement of protein synthesis for the degradation of host mRNA in Friend erythroleukemia cells infected wtih herpes simplex virus type 1. J Virol. 1978 Sep;27(3):619–627. doi: 10.1128/jvi.27.3.619-627.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Oroskar A. A., Read G. S. A mutant of herpes simplex virus type 1 exhibits increased stability of immediate-early (alpha) mRNAs. J Virol. 1987 Feb;61(2):604–606. doi: 10.1128/jvi.61.2.604-606.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Oroskar A. A., Read G. S. Control of mRNA stability by the virion host shutoff function of herpes simplex virus. J Virol. 1989 May;63(5):1897–1906. doi: 10.1128/jvi.63.5.1897-1906.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Pacha R. F., Meis R. J., Condit R. C. Structure and expression of the vaccinia virus gene which prevents virus-induced breakdown of RNA. J Virol. 1990 Aug;64(8):3853–3863. doi: 10.1128/jvi.64.8.3853-3863.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Pearson W. R., Lipman D. J. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. doi: 10.1073/pnas.85.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Peltz S. W., Brewer G., Groppi V., Ross J. Exonuclease activity that degrades histone mRNA is stable when DNA or protein synthesis is inhibited. Mol Biol Med. 1989 Jun;6(3):227–238. [PubMed] [Google Scholar]
  36. Peltz S. W., Brewer G., Kobs G., Ross J. Substrate specificity of the exonuclease activity that degrades H4 histone mRNA. J Biol Chem. 1987 Jul 5;262(19):9382–9388. [PubMed] [Google Scholar]
  37. Plotch S. J., Bouloy M., Ulmanen I., Krug R. M. A unique cap(m7GpppXm)-dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription. Cell. 1981 Mar;23(3):847–858. doi: 10.1016/0092-8674(81)90449-9. [DOI] [PubMed] [Google Scholar]
  38. Read G. S., Frenkel N. Herpes simplex virus mutants defective in the virion-associated shutoff of host polypeptide synthesis and exhibiting abnormal synthesis of alpha (immediate early) viral polypeptides. J Virol. 1983 May;46(2):498–512. doi: 10.1128/jvi.46.2.498-512.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Rice A. P., Roberts B. E. Vaccinia virus induces cellular mRNA degradation. J Virol. 1983 Sep;47(3):529–539. doi: 10.1128/jvi.47.3.529-539.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Ross J., Kobs G., Brewer G., Peltz S. W. Properties of the exonuclease activity that degrades H4 histone mRNA. J Biol Chem. 1987 Jul 5;262(19):9374–9381. [PubMed] [Google Scholar]
  41. Ross J., Kobs G. H4 histone messenger RNA decay in cell-free extracts initiates at or near the 3' terminus and proceeds 3' to 5'. J Mol Biol. 1986 Apr 20;188(4):579–593. doi: 10.1016/s0022-2836(86)80008-0. [DOI] [PubMed] [Google Scholar]
  42. Ross J. Messenger RNA turnover in eukaryotic cells. Mol Biol Med. 1988 Feb;5(1):1–14. [PubMed] [Google Scholar]
  43. Ross J., Pizarro A. Human beta and delta globin messenger RNAs turn over at different rates. J Mol Biol. 1983 Jul 5;167(3):607–617. doi: 10.1016/s0022-2836(83)80101-6. [DOI] [PubMed] [Google Scholar]
  44. Ruckman J., Parma D., Tuerk C., Hall D. H., Gold L. Identification of a T4 gene required for bacteriophage mRNA processing. New Biol. 1989 Oct;1(1):54–65. [PubMed] [Google Scholar]
  45. Schek N., Bachenheimer S. L. Degradation of cellular mRNAs induced by a virion-associated factor during herpes simplex virus infection of Vero cells. J Virol. 1985 Sep;55(3):601–610. doi: 10.1128/jvi.55.3.601-610.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Shapiro D. J., Blume J. E., Nielsen D. A. Regulation of messenger RNA stability in eukaryotic cells. Bioessays. 1987 May;6(5):221–226. doi: 10.1002/bies.950060507. [DOI] [PubMed] [Google Scholar]
  47. Shen-Ong G. L., Keath E. J., Piccoli S. P., Cole M. D. Novel myc oncogene RNA from abortive immunoglobulin-gene recombination in mouse plasmacytomas. Cell. 1982 Dec;31(2 Pt 1):443–452. doi: 10.1016/0092-8674(82)90137-4. [DOI] [PubMed] [Google Scholar]
  48. Shen S. H., Slightom J. L., Smithies O. A history of the human fetal globin gene duplication. Cell. 1981 Oct;26(2 Pt 2):191–203. doi: 10.1016/0092-8674(81)90302-0. [DOI] [PubMed] [Google Scholar]
  49. Sittman D. B., Graves R. A., Marzluff W. F. Structure of a cluster of mouse histone genes. Nucleic Acids Res. 1983 Oct 11;11(19):6679–6697. doi: 10.1093/nar/11.19.6679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Smibert C. A., Smiley J. R. Differential regulation of endogenous and transduced beta-globin genes during infection of erythroid cells with a herpes simplex virus type 1 recombinant. J Virol. 1990 Aug;64(8):3882–3894. doi: 10.1128/jvi.64.8.3882-3894.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Strom T., Frenkel N. Effects of herpes simplex virus on mRNA stability. J Virol. 1987 Jul;61(7):2198–2207. doi: 10.1128/jvi.61.7.2198-2207.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]

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