Statins demonstrate a broad anti-cytomegalovirus activity in vitro in ganciclovir-susceptible and resistant strains

Journal of Medical Virology

Volumn 87, Issue 1, 2015, Pages 141-153

  Ponroy, Nicolas ^a   Taveira, Aline ^a   Mueller, Nicolas J ^a   Millard, Anne Laure ^a  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

Antiviral activity; Endothelial cells; Ganciclovir resistance; Human cytomegalovirus (HCMV); Statins

Indexed keywords

ATORVASTATIN; CHOLESTEROL; FLUINDOSTATIN; GANCICLOVIR; GERANYLGERANYL PYROPHOSPHATE; MEVALONIC ACID; PRAVASTATIN; SIMVASTATIN; VIRUS ANTIGEN; ANTIVIRUS AGENT; HYPOCHOLESTEROLEMIC AGENT; ISOPRENOID PHOSPHATE;

ANTI CYTOMEGALOVIRUS ACTIVITY; ANTIGEN EXPRESSION; ANTIVIRAL ACTIVITY; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; CONTROLLED STUDY; EC50; ENDOTHELIUM CELL; EXOCYTOSIS; HUMAN; HUMAN AORTIC ENDOTHELIAL CELL; HUMAN CELL; HUMAN CYTOMEGALOVIRUS; IC50; IN VITRO STUDY; LUNG FIBROBLAST; NONHUMAN; REAL TIME POLYMERASE CHAIN REACTION; VIRION; VIRUS ATTACHMENT; VIRUS ENTRY; VIRUS PARTICLE; VIRUS REPLICATION; VIRUS RESISTANCE; ANTIVIRAL RESISTANCE; CELL CULTURE; CYTOMEGALOVIRUS; DRUG EFFECTS; FIBROBLAST; METABOLISM; MICROBIAL SENSITIVITY TEST;

ANTICHOLESTEREMIC AGENTS; ANTIVIRAL AGENTS; CELLS, CULTURED; CHOLESTEROL; CYTOMEGALOVIRUS; DRUG RESISTANCE, VIRAL; ENDOTHELIAL CELLS; FIBROBLASTS; GANCICLOVIR; HUMANS; MEVALONIC ACID; MICROBIAL SENSITIVITY TESTS; POLYISOPRENYL PHOSPHATES;

EID: 84909999604     PISSN: 01466615     EISSN: 10969071     Source Type: Journal    
DOI: 10.1002/jmv.23998     Document Type: Article

References (67)

1. Bader T, Fazili J, Madhoun M, Aston C, Hughes D, Rizvi S, Seres K, Hasan M. 2008. Fluvastatin inhibits hepatitis C replication in humans. Am J Gastroenterol 103:1383-1389.
2. Benedict CA, Angulo A, Patterson G, Ha S, Huang H, Messerle M, Ware CF, Ghazal P. 2004. Neutrality of the canonical NF-kappaB-dependent pathway for human and murine cytomegalovirus transcription and replication in vitro. J Virol 78:741-750.
3. Biasucci LM, Biasillo G, Stefanelli A. 2010. Inflammatory markers, cholesterol and statins: Pathophysiological role and clinical importance. Clin Chem Lab Med 48:1685-1691.
4. Biron KK. 2006. Antiviral drugs for cytomegalovirus diseases. Antiviral Res 71:154-163.
5. Blanc M, Hsieh WY, Robertson KA, Watterson S, Shui G, Lacaze P, Khondoker M, Dickinson P, Sing G, Rodriguez-Martin S, Phelan P, Forster T, Strobl B, Muller M, Riemersma R, Osborne T, Wenk MR, Angulo A, Ghazal P. 2011. Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis. PLoS Biol 9:e1000598.
6. Blankenberg S, Rupprecht HJ, Bickel C, Espinola-Klein C, Rippin G, Hafner G, Ossendorf M, Steinhagen K, Meyer J. 2001. Cytomegalovirus infection with interleukin-6 response predicts cardiac mortality in patients with coronary artery disease. Circulation 103:2915-2921.
7. Boettner B, Van Aelst L. 2002. The role of Rho GTPases in disease development. Gene 286:155-174.
8. Cheng J, Ke Q, Jin Z, Wang H, Kocher O, Morgan JP, Zhang J, Crumpacker CS. 2009. Cytomegalovirus infection causes an increase of arterial blood pressure. PLoS Pathog 5:e1000427.
9. Chou S, Waldemer RH, Senters AE, Michels KS, Kemble GW, Miner RC, Drew WL. 2002. Cytomegalovirus UL97 phosphotransferase mutations that affect susceptibility to ganciclovir. J Infect Dis 185:162-169.
10. Cohen JI, Corey GR. 1985. Cytomegalovirus infection in the normal host. Medicine (Baltimore) 64:100-114.
11. Cook CH, Bickerstaff AA, Wang JJ, Zimmerman PD, Forster MR, Nadasdy T, Colvin RB, Hadley GA, Orosz CG. 2009. Disruption of murine cardiac allograft acceptance by latent cytomegalovirus. Am J Transplant 9:42-53.
12. Corsini A, Bellosta S, Baetta R, Fumagalli R, Paoletti R, Bernini F. 1999. New insights into the pharmacodynamic and pharmacokinetic properties of statins. Pharmacol Ther 84:413-428.
13. del Real G, Jimenez-Baranda S, Mira E, Lacalle RA, Lucas P, Gomez-Mouton C, Alegret M, Pena JM, Rodriguez-Zapata M, Alvarez-Mon M, Martinez AC, Manes S. 2004. Statins inhibit HIV-1 infection by down-regulating Rho activity. J Exp Med 200:541-547.
14. Delang L, Paeshuyse J, Vliegen I, Leyssen P, Obeid S, Durantel D, Zoulim F, Op de Beeck A, Neyts J. 2009. Statins potentiate the in vitro anti-hepatitis C virus activity of selective hepatitis C virus inhibitors and delay or prevent resistance development. Hepatology 50:6-16.
15. Dengler TJ, Raftery MJ, Werle M, Zimmermann R, Schonrich G. 2000. Cytomegalovirus infection of vascular cells induces expression of pro-inflammatory adhesion molecules by paracrine action of secreted interleukin-1beta. Transplantation 69:1160-1168.
16. Desplanques AS, Pontes M, De Corte N, Verheyen N, Nauwynck HJ, Vercauteren D, Favoreel HW. 2010. Cholesterol depletion affects infectivity and stability of pseudorabies virus. Virus Res 152:180-183.
17. Eickhoff JE, Cotten M. 2005. NF-kappaB activation can mediate inhibition of human cytomegalovirus replication. J Gen Virol 86:285-295.
18. Endo A, Kuroda M, Tsujita Y. 1976. ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by Penicillium citrinium. J Antibiot (Tokyo) 29:1346-1348.
19. Fish KN, Soderberg-Naucler C, Mills LK, Stenglein S, Nelson JA. 1998. Human cytomegalovirus persistently infects aortic endothelial cells. J Virol 72:5661-5668.
20. Gilbert C, Boivin G. 2005. Human cytomegalovirus resistance to antiviral drugs. Antimicrob Agents Chemother 49:873-883.
21. Gohring K, Mikeler E, Jahn G, Hamprecht K. 2006. Rapid simultaneous detection by real-time PCR of cytomegalovirus UL97 mutations in codons 460 and 520 conferring ganciclovir resistance. J Clin Microbiol 44:4541-4544.
22. Hamelin BA, Turgeon J. 1998. Hydrophilicity/lipophilicity: Relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol Sci 19:26-37.
23. Horvath R, Cerny J, Benedik J Jr, Hokl J, Jelinkova I, Benedik J. 2000. The possible role of human cytomegalovirus (HCMV) in the origin of atherosclerosis. J Clin Virol 16:17-24.
24. Hwang JS, Schilf R, Drach JC, Townsend LB, Bogner E. 2009. Susceptibilities of human cytomegalovirus clinical isolates and other herpesviruses to new acetylated, tetrahalogenated benzimidazole d-ribonucleosides. Antimicrob Agents Chemother 53:5095-5101.
25. Ikeda M, Abe K, Yamada M, Dansako H, Naka K, Kato N. 2006. Different anti-HCV profiles of statins and their potential for combination therapy with interferon. Hepatology 44:117-125.
26. Jarvis MA, Nelson JA. 2002. Human cytomegalovirus persistence and latency in endothelial cells and macrophages. Curr Opin Microbiol 5:403-407.
27. Kahl M, Siegel-Axel D, Stenglein S, Jahn G, Sinzger C. 2000. Efficient lytic infection of human arterial endothelial cells by human cytomegalovirus strains. J Virol 74:7628-7635.
28. Kapur NK, Musunuru K. 2008. Clinical efficacy and safety of statins in managing cardiovascular risk. Vasc Health Risk Manag 4:341-353.
29. Kobashigawa JA, Katznelson S, Laks H, Johnson JA, Yeatman L, Wang XM, Chia D, Terasaki PI, Sabad A, Cogert GA, Trosian K, Hamilton MA, Moriguchi JD, Kawata N, Hage A, Drinkwater DC, Stevenson LW. 1995. Effect of pravastatin on outcomes after cardiac transplantation. N Engl J Med 333:621-627.
30. Lemstrom KB, Koskinen PK, Bruning JH, Bruggeman CA, Lautenschlager IT, Hayry PJ. 1994. Effect of ganciclovir prophylaxis on cytomegalovirus-enhanced allograft arteriosclerosis. Transplant Int 7:S383-S384.
31. Liao JK, Laufs U. 2005. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 45:89-118.
32. Lischka P, Hewlett G, Wunberg T, Baumeister J, Paulsen D, Goldner T, Ruebsamen-Schaeff H, Zimmermann H. 2010. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246. Antimicrob Agents Chemother 54:1290-1297.
33. Liu S, Rodriguez AV, Tosteson MT. 2006. Role of simvastatin and methyl-beta-cyclodextrin [corrected] on inhibition of poliovirus infection. Biochem Biophys Res Commun 347:51-59.
34. Lurain NS, Bhorade SM, Pursell KJ, Avery RK, Yeldandi VV, Isada CM, Robert ES, Kohn DJ, Arens MQ, Garrity ER, Taege AJ, Mullen MG, Todd KM, Bremer JW, Yen-Lieberman B. 2002. Analysis and characterization of antiviral drug-resistant cytomegalovirus isolates from solid organ transplant recipients. J Infect Dis 186:760-768.
35. Mahy B, Kangro H. editors. 1996. Virology methods manual. London, UK: Academic Press Ltd.
36. Malaguarnera M, Vacante M, Russo C, Gargante MP, Giordano M, Bertino G, Neri S, Galvano F, Li Volti G. 2011. Rosuvastatin reduces nonalcoholic fatty liver disease in patients with chronic hepatitis C treated with alpha-interferon and ribavirin: Rosuvastatin reduces NAFLD in HCV patients. Hepat Mon 11:92-98.
37. Martinez-Gutierrez M, Castellanos JE, Gallego-Gomez JC. 2011. Statins reduce dengue virus production via decreased virion assembly. Intervirology 54:202-216.
38. Mehra MR, Raval NY. 2004. Metaanalysis of statins and survival in de novo cardiac transplantation. Transplant Proc 36:1539-1541.
39. Mercorelli B, Lembo D, Palu G, Loregian A. 2011. Early inhibitors of human cytomegalovirus: State-of-art and therapeutic perspectives. Pharmacol Ther 131:309-329.
40. Millard AL, Haberli L, Sinzger C, Ghielmetti M, Schneider MK, Bossart W, Seebach JD, Mueller NJ. 2010. Efficiency of porcine endothelial cell infection with human cytomegalovirus depends on both virus tropism and endothelial cell vascular origin. Xenotransplantation 17:274-287.
41. Mocarski ES. 1996. Cytomegaloviruses and their replication. In: Fields B, Knipe D, Howley P, editors. Field's virology. 3rd edition. Philadelphia: Lippincott-Raven Press, pp 2447-2492.
42. Mohan KV, Muller J, Atreya CD. 2008. Defective rotavirus particle assembly in lovastatin-treated MA104 cells. Arch Virol 153:2283-2290.
43. Montecucco F, Mach F. 2009. Update on statin-mediated anti-inflammatory activities in atherosclerosis. Semin Immunopathol 31:127-142.
44. Muhlestein JB, Horne BD, Carlquist JF, Madsen TE, Bair TL, Pearson RR, Anderson JL. 2000. Cytomegalovirus seropositivity and C-reactive protein have independent and combined predictive value for mortality in patients with angiographically demonstrated coronary artery disease. Circulation 102:1917-1923.
45. Pescovitz MD, Jain A, Robson R, Mulgaonkar S, Freeman R, Bouw MR. 2007. Establishing pharmacokinetic bioequivalence of valganciclovir oral solution versus the tablet formulation. Transplant Proc 39:3111-3116.
46. Petrakopoulou P, Kubrich M, Pehlivanli S, Meiser B, Reichart B, von Scheidt W, Weis M. 2004. Cytomegalovirus infection in heart transplant recipients is associated with impaired endothelial function. Circulation 110:II207-212.
47. Potena L, Frascaroli G, Grigioni F, Lazzarotto T, Magnani G, Tomasi L, Coccolo F, Gabrielli L, Magelli C, Landini MP, Branzi A. 2004. Hydroxymethyl-glutaryl coenzyme a reductase inhibition limits cytomegalovirus infection in human endothelial cells. Circulation 109:532-536.
48. Potena L, Holweg CT, Chin C, Luikart H, Weisshaar D, Narasimhan B, Fearon WF, Lewis DB, Cooke JP, Mocarski ES, Valantine HA. 2006. Acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection. Transplantation 82:398-405.
49. Potena L, Valantive H. 2010. Cytomegalovirus and development of cardiac allograft vasculopathy: Evidences and therapeutic implications. Trends Transplant 4:108-116.
50. Rubin RH. 2007. The pathogenesis and clinical management of cytomegalovirus infection in the organ transplant recipient: The end of the 'silo hypothesis'. Curr Opin Infect Dis 20:399-407.
51. Sakamoto K, Mikami H, Kimura J. 2008. Involvement of organic anion transporting polypeptides in the toxicity of hydrophilic pravastatin and lipophilic fluvastatin in rat skeletal myofibres. Br J Pharmacol 154:1482-1490.
52. Schreiber A, Harter G, Schubert A, Bunjes D, Mertens T, Michel D. 2009. Antiviral treatment of cytomegalovirus infection and resistant strains. Expert Opin Pharmacother 10:191-209.
53. Schweitzer M, Mitmaker B, Obrand D, Sheiner N, Abraham C, Dostanic S, Meilleur M, Sugahara T, Chalifour LE. 2010. Atorvastatin modulates matrix metalloproteinase expression, activity, and signaling in abdominal aortic aneurysms. Vasc Endovascular Surg 44:116-122.
54. Senchenkov E, Khoretonenko MV, Leskov IL, Ostanin DV, Stokes KY. 2011. P-selectin mediates the microvascular dysfunction associated with persistent cytomegalovirus infection in normocholesterolemic and hypercholesterolemic mice. Microcirculation 18:452-462.
55. Sindre H, Haraldsen G, Beck S, Hestdal K, Kvale D, Brandtzaeg P, Degre M, Rollag H. 2000. Human intestinal endothelium shows high susceptibility to cytomegalovirus and altered expression of adhesion molecules after infection. Scand J Immunol 51:354-360.
56. Sinzger C, Digel M, Jahn G. 2008. Cytomegalovirus cell tropism. Curr Top Microbiol Immunol 325:63-83.
57. Sinzger C, Grefte A, Plachter B, Gouw AS, The TH, Jahn G. 1995. Fibroblasts, epithelial cells, endothelial cells and smooth muscle cells are major targets of human cytomegalovirus infection in lung and gastrointestinal tissues. J Gen Virol 76:741-750.
58. Sinzger C, Kahl M, Laib K, Klingel K, Rieger P, Plachter B, Jahn G. 2000. Tropism of human cytomegalovirus for endothelial cells is determined by a post-entry step dependent on efficient translocation to the nucleus. J Gen Virol 81:3021-3035.
59. Takai Y, Sasaki T, Matozaki T. 2001. Small GTP-binding proteins. Physiol Rev 81:153-208.
60. Taylor DO, Edwards LB, Boucek MM, Trulock EP, Aurora P, Christie J, Dobbels F, Rahmel AO, Keck BM, Hertz MI. 2007. Registry of the International Society for Heart and Lung Transplantation: Twenty-fourth official adult heart transplant report-2007. J Heart Lung Transplant 26:769-781.
61. Wang C, Gale M Jr, Keller BC, Huang H, Brown MS, Goldstein JL, Ye J. 2005. Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. Mol Cell 18:425-434.
62. Weis M, Pehlivanli S, Meiser BM, von Scheidt W. 2001. Simvastatin treatment is associated with improvement in coronary endothelial function and decreased cytokine activation in patients after heart transplantation. J Am Coll Cardiol 38:814-818.
63. Wenke K, Meiser B, Thiery J, Nagel D, von Scheidt W, Krobot K, Steinbeck G, Seidel D, Reichart B. 2003. Simvastatin initiated early after heart transplantation: 8-Year prospective experience. Circulation 107:93-97.
64. Ye J, Wang C, Sumpter R Jr, Brown MS, Goldstein JL, Gale M Jr. 2003. Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc Natl Acad Sci USA 100:15865-15870.
65. Yun Z, Lewensohn-Fuchs I, Ljungman P, Vahlne A. 2000. Real-time monitoring of cytomegalovirus infections after stem cell transplantation using the TaqMan polymerase chain reaction assays. Transplantation 69:1733-1736.
66. Zeiser R, Maas K, Youssef S, Durr C, Steinman L, Negrin RS. 2009. Regulation of different inflammatory diseases by impacting the mevalonate pathway. Immunology 127:18-25.
67. Zhu J, Quyyumi AA, Norman JE, Csako G, Waclawiw MA, Shearer GM, Epstein SE. 2000. Effects of total pathogen burden on coronary artery disease risk and C-reactive protein levels. Am J Cardiol 85:140-146.