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Metal complexes of bovine lactoferrin inhibit in vitro replication of herpes simplex virus type 1 and 2

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Abstract

The inhibitory effect of bovine lactoferrin (BLf) saturated with ferric, manganese or zinc ions, on the infection of Vero cells by human herpes simplex virus type 1 (HSV1) and 2 (HSV2) was investigated. Viral infectivity determined by intracellular antigen synthesis and plaque formation was efficiently inhibited by metal saturated lactoferrins in a dose-dependent manner. Effective BLf concentrations which reduced the infection by 50% ranged from 5.2 to 31 mug ml and were far below the cytotoxicity threshold. Fe BLf and Mn BLf exhibited selectivity indexes higher than Zn BLf and apoBLf for both viruses and the effect was mainly directed towards the early steps of infection. The slight viral inhibition shown by the citrate complexes of the different metals could indicate that the antiviral effect was not significantly influenced by Fe , Mn or Zn ions delivered by BLf into the cells. © Rapid Science 1998

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References

  • Alugupalli KR. 1996 Lactoferrin interactions with periodontitis-associated bacteria. In: Alugupalli KR ed. Aspects of adhesion-counteracting mechanisms. Lund University Graphic Systems AB; 1–45.

  • Baker EN, Anderson BF, Baker HM et al. 1994 Three-dimensional structure of lactoferrin in various functional states. Adv Exp Med Biol 357, 1–12.

    Google Scholar 

  • Balogh-Nair V, Brathwaite CE, Chen CX, Vargas J Jr. 1995 Synthesis, activity and toxicity of novel macrocyclic ligands against HIV-1 in Jurkat and CEM-SS cell lines. Cell Mol Biol 41, 9–14.

    Google Scholar 

  • Cinatl J Jr, Cinatl J, Rabenau H et al. 1994 In vitro inhibition of human cytomegalovirus replication by desferrioxamine. Antiviral Res 25, 73–77.

    Google Scholar 

  • Cinatl J Jr, Hoffmann F, Cinatl J, et al, 1996 In vitro inhibition of human cytomegalovirus replication by calcium trinatrium diethylenetriaminepentaacetic acid. Antiviral Res 31, 23–34.

    Google Scholar 

  • Comerie-Smith SE, Nunez J, Hosmer M, Farris RL. 1994 Tear lactoferrin and ocular bacterial flora in HIV positive patients. Adv Exp Med Biol 350, 339–344.

    Google Scholar 

  • Dai Y, Gold B, Vishwanatha JK, Rhode SL. 1994 Mimosine inhibits viral DNA synthesis through ribonucleotide reductase. Virology 205, 210–216.

    Google Scholar 

  • Davidson LA, Lonnerdal B. 1989 Fe saturation and proteolysis of human lactoferrin: effect on brushborder receptor mediated uptake of Fe2+ and Mn2+. Am J Physiol 257, G930-G934.

    Google Scholar 

  • Defer MC, Dugas B, Picard O, Damais C. 1995 Impairment of circulating lactoferrin in HIV-infection. Cell Mol Biol 41, 417–421.

    Google Scholar 

  • Fujihara, T, Hayashi K. 1995 Lactoferrin inhibits herpes simplex virus type-1 (HSV-1) infection to mouse cornea. Arch Virol 140, 1469–1472.

    Google Scholar 

  • Harmsen MC, Swart PJ, de Béthune MP et al. 1995 Antiviral effects of plasma and milk proteins: lactoferrin shows a potent activity against both human immunodeficiency virus and human cytomegalovirus replication in vitro. J Infect Dis 172, 380–388.

    Google Scholar 

  • Hasegawa K, Motsuchi W, Tanaka S, Dosako S. 1994 Inhibition with lactoferrin of in vitro infection with human herpes virus. Jpn J Med Sci Biol 47, 73–85.

    Google Scholar 

  • Hu W-L, Mazurier J, Montreuil J, Spik G. 1990 Isolation and partial characterization of a lactotransferrin receptor from mouse intestinal brush border. Biochemistry 29 535–541.

    Google Scholar 

  • Inouye Y, Kanomori T, Yoshida T et al. 1994 Inhibition of human immunodeficiency virus proliferation by macrocyclic polyamines and their metal complexes. Biol Pharm Bull 17, 243–250.

    Google Scholar 

  • Kriegerbeckova K, Dopper L, Scheiver B, Kovar J, Goldenberg H. 1995 Non-transferrin iron uptake by HeLa cells cultured in serum-free media with different iron sources. Eur J Clin Chem Biochem 33, 791–797.

    Google Scholar 

  • Levay PF, Viljoen M. 1995 Lactoferrin: a general review. Haematologica 80, 252–67.

    Google Scholar 

  • Liuzzi M, DÆeziel R, Moss N et al. 1994 A potent peptidomimetic inhibitor of HSV ribonucleotide reductase with antiviral activity in vivo. Nature 372, 6507–6508.

    Google Scholar 

  • Marchetti M, Longhi C, Conte MP et al. 1996a Lactoferrin inhibits herpes simplex virus type 1 adsorption to Vero cells. Antiviral Res 29 221–231.

    Google Scholar 

  • Marchetti M, Pisani S, Pietropaolo V et al. 1996b Antiviral effect of a polysaccharide from Sclerotium glucanicum towards herpes simplex virus type 1 infection. Planta Medica 62, 303–307.

    Google Scholar 

  • McAbee DD. 1995 Isolated rat hepatocytes acquire iron from lactoferrin by endocytosis. Biochem J 311, 603–609.

    Google Scholar 

  • Nuijens JH, Abbink JJ, Wachtfogel YT et al. 1992 Plasma elastase alpha 1-antitrypsin and lactoferrin in sepsis: evidence for neutrophils as mediators in fatal sepsis. J Lab Clin Med 119, 159–168.

    Google Scholar 

  • Sanchez L, Ismail M, Liew FY, Brock JH. 1996 Iron Transport across Caco-2 cell monolayers. Effect of transferrin, lactoferrin and nitric oxide. Biochim Biophys Acta 1289(2), 291–297.

    Google Scholar 

  • Shimizu K, Matsuzawa H, Okada K et al. 1996 Lactoferrin-mediated protection of the host from murine cytomegalovirus infection by a T-cell-dependent augmentation of natural killer cell activity. Arch Virol 141, 1875–1889.

    Google Scholar 

  • Soerensen M, Soerensen SPL. 1939 The protein in whey. C R Trav Lab Carlsberg 23, 55–99.

    Google Scholar 

  • Spector T, Harrington JA, Morrison RW Jr et al. 1989 2-Acetylpyridine 5-[(dimethylamino)thiocarbonyl]thiocarbonohydrazone (1110U81), a potent inactivator of ribonucleotide reductase of herpes simplex and varicellazoster viruses and a potentiator of a acyclovir. Proc Natl Acad Sci USA 86, 1051–1055.

    Google Scholar 

  • Spector T, Harrington JA, Porter DJT. 1991 Herpes and human ribonucleotide reductases: inhibition by 2-acetylpyridine 5-[(2-chloroanilino) thiocarbonyl]thiocarbonohydrazone (348U87). Biochem Pharmacol 42 91–96.

    Google Scholar 

  • Swart PJ, Kuipers ME, Smith C et al. 1996 Antiviral effects of milk proteins: acylation results in polyanionic compounds with potent activity against human immunodeficiency virus types 1 and 2 in vitro. AIDS Res Human Retrov 12, 769–775.

    Google Scholar 

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Marchetti, M., Pisani, S., Antonini, G. et al. Metal complexes of bovine lactoferrin inhibit in vitro replication of herpes simplex virus type 1 and 2. Biometals 11, 89–94 (1998). https://doi.org/10.1023/A:1009217709851

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