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Herpes simplex virus type 1 propagation in HeLa cells interrupted by Nelumbo nucifera

  • Published:
Journal of Biomedical Science

Summary

Inhibitory effects of ethanolic extracts from 10 Chinese herbs on herpes simplex virus type 1 (HSV-1) replication were investigated. By a bioassay-guided fractionation procedure, NN-B-5 was identified from seeds of N. nucifera. NN-B-5 significantly blocked HSV-1 multiplication in HeLa cells without apparent cytotoxicity. To elucidate the point in HSV-1 replication where arrest occurred, a set of key regulatory events leading to the viral multiplication was examined, including HSV-1 DNA synthesis and viral immediate early gene expressions. Data from polymerase chain reaction and Southern blotting showed that there were impairments of HSV-1 DNA replication in HeLa cells treated with NN-B-5. Results indicated that the production and mRNA transcription of infected cell protein (ICP) 0 and ICP4 were decreased in NN-B-5 treated HeLa cells. Results of an electrophoretic mobility shift assay demonstrated that NN-B-5 interrupted the formation of α-trans-induction factor/C1/Oct-1/GARAT multiprotein/DNA complexes. The mechanisms of antiviral action of NN-B-5 seem to be mediated, at least in part, through inhibition of immediate early transcripts, such as ICP0 and ICP4 mRNA and then blocking of all downstream viral products accumulation and progeny HSV-1 production.

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References

  1. Roizman B, Sears AE (1996) Herpes Simplex Virus and Their Replication. In: Fields BN, Knipe DM, Howley PM, (eds) Fundamental Virology. Lippincott-Raven Publishers, Philadelphia, pp. 2231–2295

    Google Scholar 

  2. Pass RF, Long WK, Whitley RJ, Soong SJ, Diethelm AG, Reynolds DW, Alford CA Jr. (1978) Productive infection with cytomegalovirus and herpes simplex virus in renal transplant recipients: role of source kidney. J Infect Dis 137:556–563

    PubMed  CAS  Google Scholar 

  3. Waggoner-Fountain LA, Grossman LB (2004) Herpes simplex virus. Pediatr Rev 25:86–93

    Article  PubMed  Google Scholar 

  4. Stranska R, van Loon AM, Bredius RG, Polman M, Nienhuis E, Beersma MF, Lankester AC, Schuurman R (2004) Sequential switching of DNA polymerase and thymidine kinase-mediated HSV-1 drug resistance in an immunocompromised child. Antivir Ther 9:97–104

    PubMed  Google Scholar 

  5. Chen H, Teng L, Li JN, Park R, Mold DE, Gnabre J, Hwu JR, Tseng WN, Huang RC (1998) Antiviral activities of methylated nordihydroguaiaretic acids. 2. Targeting herpes simplex virus replication by the mutation insensitive transcription inhibitor tetra-O-methyl-NDGA. J Med Chem 41:3001–3007

    Article  PubMed  CAS  Google Scholar 

  6. Mann SL, Meyers JD, Holmes KL, Corey L (1984) Prevalence and incidence of herpesvirus infections among homosexually active men. J Infect Dis 149:1026–1027

    PubMed  CAS  Google Scholar 

  7. Corey L, Wald A, Celum CL, Quinn TC (2004) The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: A review of two overlapping epidemics. J Acquir Immune Defic Syndr 35:435–445

    Article  PubMed  Google Scholar 

  8. Honess RW, Roizman B (1975) Regulation of herpesvirus macromolecular synthesis: sequential transition of polypeptide synthesis required functional viral polypeptides. Proc Natl Acad Sci USA 72:1276–1280

    Article  PubMed  CAS  Google Scholar 

  9. McKnight JLC, Kristie TM, Roizman B (1987) Binding of the virion protein mediating α gene induction in herpes simplex virus 1-infected cells to its cis site required cellular proteins. Proc Natl Acad Sci USA 84:7061–7065

    Article  PubMed  CAS  Google Scholar 

  10. Darby G (1994) A history of antiherpes research. Antivir Chem Chemother 5(Suppl. 1):3–9

    CAS  Google Scholar 

  11. Imai Y, Shum C, Martin DF, Kuppermann BD, Drew WL, Margolis TP (2004) Emergence of drug-resistant cytomegalovirus retinitis in the contralateral eyes of patients with AIDS treated with ganciclovir. J Infect Dis 189:611–615

    Article  PubMed  Google Scholar 

  12. Elion GB, Furman PA, Fyfe JA, Miranda Pde, Beauchamp L, Schaeffer HJ (1977) Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. Proc Natl Acad Sci USA 74:5716–5720

    Article  PubMed  CAS  Google Scholar 

  13. Furman PA, Clair MH St, Fyfe JA, Rideout JL, Keller PM, Elion GB (1979) Inhibition of herpes simplex virus-induced DNA polymerase activity and viral DNA replication by 9-(2-hydroxyethoxymethyl) guanine and its triphosphate. J Virol 32:72–77

    PubMed  CAS  Google Scholar 

  14. Coen DM (1996) Antiviral drug resistance in herpes simplex virus. Adv Exp Med Biol 394:49–57

    PubMed  CAS  Google Scholar 

  15. Kimberlin DW, Whitley RJ (1996) Antiviral resistance: mechanisms, clinical significance, and future implications. J Antimicrob Chemoth 37:403–421

    Article  PubMed  CAS  Google Scholar 

  16. Chibo D, Druce J, Sasadeusz J, Birch C (2004) Molecular analysis of clinical isolates of acyclovir resistant herpes simplex virus. Antivir Res 61:83–91

    Article  PubMed  CAS  Google Scholar 

  17. Kuo YC, Yang NS, Chou CJ, Lin LC, Tsai WJ (2000) Regulation of cell proliferation, gene expression, production of cytokines, and cell cycle progression in primary human T lymphocytes by piperlactam S isolated from Piper kadsura. Mol Pharmacol 58:1057–1066

    PubMed  CAS  Google Scholar 

  18. Kuo YC, Sun CM, Ou JC, Tsai WJ (1997) A tumor cell growth inhibitor from Polygonum hypoleucum Ohwi. Life Sci 61:2335–2344

    Article  PubMed  CAS  Google Scholar 

  19. Marchetti M, Pisani S, Pietropaola V, Seganti L, Nicoletti R, Degener A, Orsi N (1996) Antiviral effect of a polysaccharide from Sclerotium glucanicum towards herpes simplex virus type 1 infection. Planta Medica 62:303–307

    Article  PubMed  CAS  Google Scholar 

  20. Sydiskis RJ, Owen DG, Lohr JL, Rosler KH, Blomster RN (1991) Inactivation of enveloped viruses by anthraquinones extracted from plants. Antimicrob Agents Chemother 35:2463–2466

    PubMed  CAS  Google Scholar 

  21. Simõnes CMO, Amoros M, Girre L (1999) Mechanism of antiviral activity of triterpenoid saponins. Phytother Res 21:317–325

    Google Scholar 

  22. Arisawa M, Fujita A, Hayashi T, Hayashi K, Ochiai H, Morita N (1990) Cytotoxic and antiherpetic activity of phloroglucinol derivatives from Mallotus japonicus (Euphorbiaceae). Chem Pharm Bull 38:1624–1626

    PubMed  CAS  Google Scholar 

  23. Kuo YC, Lin LC, Tsai WJ, Chou CJ, Kung SH, Ho YH (2002) Samaragenin B identified from Limonium sinense suppressed herpes simplex virus type 1 replication in Vero cells by regulation of viral macromolecular synthesis. Antimicrob Agents Ch 46:2854–2864

    Article  PubMed  CAS  Google Scholar 

  24. Ferrea G, Canessa A, Sampietro F, Cruciani M, Romussi G, Bassetti D (1993) In vitro activity of a Combretum micranthum extract against herpes simplex virus types 1 and 2. Antivir Res 21:317–325

    Article  PubMed  CAS  Google Scholar 

  25. Alrabiah FA, Sacks SL (1996) New antiherpes virus agents: Their targets and therapeutic potential. Drugs 52:17–32

    Article  PubMed  CAS  Google Scholar 

  26. Pope LE, Marceletti JF, Katz LR, Katz DH (1996) Anti-herpes simplex virus activity of n-docosanol correlates with intracellular metabolic conversion of the drug. J Lipid Res 37:2167–2178

    PubMed  CAS  Google Scholar 

  27. Sacks SL, Thisted RA, Jones TM, Barbarash RA, Mikolich DJ, Ruoff GE, Jorizzo JL, Gunnill LB, Katz DH, Khalil MH, Morrow PRG, Yakatan J, Pope LE, Berge JE (2001) The Docosanol 10% Cream Study Group. Clinical efficacy of topical docosanol 10% cream for herpes simplex labialis: A multicenter, randomized, placebo-controlled trial. J Am Acad Dermatol 45:222–230

    Article  PubMed  CAS  Google Scholar 

  28. Betz UAK, Fischer R, Kleymann G, Hendrix M, Rübsamen-Waigmann H (2002) Potent in vivo antiviral activity of the herpes simplex virus primase-helicase inhibitor BAY 57–1293. Antimicrob Agents Ch 46:1766–1772

    Article  PubMed  CAS  Google Scholar 

  29. Kleymann G., Fischer R, Betz UAK, Hendrix M, Bender W, Schneider U, Handke G, Eckenberg P, Hewlett G, Pevzner V, Baumeister J, Weber O, Henninger K, Keldenich J, Jensen A, Kolb J, Bach I, Popp A, Mäben J, Frappa I, Haebich D, Lockhoff O, Rübsamen-Waigmann H (2002) New helicase-primase inhibitors as drug candidates for the treatment of herpes simplex disease. Nat Med 8:392–398

    Article  PubMed  CAS  Google Scholar 

  30. Kuo YC, Chen CC, Tsai WJ, Ho YH (2001) Regulation of herpes simplex virus type 1 replication in Vero cells by Psychotria serpens: relationship to gene expression, DNA replication, and protein synthesis. Antivir Res 51:95–109

    Article  PubMed  CAS  Google Scholar 

  31. Kuo YC, Liu WT, Lin CY (1993) Herpes simplex virus type 1 genes in human mononuclear cells and affecting cell-mediated immunity. J Med Virol 41:138–145

    Article  PubMed  CAS  Google Scholar 

  32. Saiki PK, Scharf S, Faloona F, Mullis KB, Horn G, Erlich HA, Arnheim N (1985) Enzymatic amplification of globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230:1350–1354

    Article  PubMed  CAS  Google Scholar 

  33. Cone RW, Hobson AC, Palmer J, Remington M, Corey L (1991) Extended duration of herpes simplex virus DNA in genital lesions detected by the polymerase chain reaction. J Infect Dis 164:757–760

    PubMed  CAS  Google Scholar 

  34. Bacon TH, Howard BA, Spender LC, Boyd MR (1996) Activity of penciclovir in antiviral assays against herpes simplex virus. J Antimicrob Chemoth 37:303–313

    Article  PubMed  CAS  Google Scholar 

  35. Qian JQ (2002) Cardiovascular pharmacological effects of bisbenzylisoquinoline alkaloid derivatives. Acta Pharmacol Sin 23:1086–92

    PubMed  CAS  Google Scholar 

  36. Yu J, Hu WS (1997) Effects of neferine on platelet aggregation in rabbits. Yao Xue Xue Bao 32:1–4

    PubMed  CAS  Google Scholar 

  37. Mackem S, Roizman B (1982) Structural features of the herpes simplex alpha gene 4, 0, 27 promoter-regulatory sequences which confer a regulation on chimeric thymidine kinase genes. J Virol 44:939–949

    PubMed  CAS  Google Scholar 

  38. Jones PC, Roizman B (1979) Regulation of herpesvirus macromolecular synthesis: VIII. The transcription program consists of three phases during which both extent of transcription and accumulation of RNA in the cytoplasm are regulated. J Virol 31:299–314

    PubMed  CAS  Google Scholar 

  39. Honess RW, Roizman B (1974) Regulation of herpesvirus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins. J Virol 14:8–19

    PubMed  CAS  Google Scholar 

  40. Hoshino T, Hayashi T, Hayashi K, Hamada J, Lee JB, Sankawa U (1998) An antivirally active sulfated polysaccharide from Sargassum horneri (Turner) C. Agardh Biol Pharm Bull 21:730–734

    CAS  Google Scholar 

  41. 5. Boulware SL, Bronstein JC, Nordby EC, Weber PC (2001) Identification and characterization of a benzothiophene inhibitor of herpes simplex virus type 1 replication which acts at the immediate early stage of infection. Antivir Res 51:111–125

    Article  PubMed  CAS  Google Scholar 

  42. Kramer MF, Coen DM (1995) Quantification of transcripts from the ICP4 and thymidine kinase genes in mouse ganglia latently infected with herpes simplex virus. J Virol 69:1389–1399

    PubMed  CAS  Google Scholar 

  43. Feldman LT, Ellison AR, Voytek CC, Yang L, Krause P, Margolis TP (2002) Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice. Proc Natl Acad Sci USA 99:978–983

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This study was partially supported by grants-in aid from The National Science Council, Republic of China (NSC92-2323-B-030-014; NSC92-2320-B-030-001). We thank Priscilla Schaffer’s Laboratory that the HSV-1 KOS strain originally came from.

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Authors and Affiliations

  1. Institute of Life Science, Fu-Jen University, Taipei, Taiwan, R.O.C

    Yuh-Chi Kuo

  2. National Research Institute of Chinese Medicine, Taipei, Taiwan, R.O.C

    Yun-Lian Lin & Wei-Jern Tsai

  3. Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, R.O.C

    Chih-Peng Liu

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  1. Yuh-Chi Kuo
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  2. Yun-Lian Lin
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  4. Wei-Jern Tsai
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Correspondence to Wei-Jern Tsai.

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Kuo, YC., Lin, YL., Liu, CP. et al. Herpes simplex virus type 1 propagation in HeLa cells interrupted by Nelumbo nucifera . J Biomed Sci 12, 1021–1034 (2005). https://doi.org/10.1007/s11373-005-9001-6

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  • DOI: https://doi.org/10.1007/s11373-005-9001-6

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