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Resistance of Herpesviruses to Antiviral Agents

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Antimicrobial Resistance and Implications for the Twenty-First Century

Part of the book series: Emerging Infectious Diseases of the 21 Century ((EIDC))

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References

  • Baldanti, F., Lilleri, D., Campanini, G., Comolli, G., Ridolfo, A.L., Rusconi, S. and Gerna, G., (2004), Human cytomegalovirus double resistance in a donor-positive/recipient-negative lung transplant patient with an impaired CD4-mediated specific immune response. J Antimicrob Chemother, 53, 536–539.

    PubMed  CAS  Google Scholar 

  • Baldanti, F., Michel, D., Simoncini, L., Heuschmid, M., Zimmermann, A., Minisini, R., Schaarschmidt, P., Schmid, T., Gerna, G. and Mertens, T., (2002), Mutations in the UL97 orf of ganciclovir-resistant clinical cytomegalovirus isolates differentially affect GCV phosphorylation as determined in a recombinant vaccinia virus system. Antiviral Res, 54, 59–67.

    PubMed  CAS  Google Scholar 

  • Baldanti, F., Silini, E., Sarasini, A., Talarico, C.L., Stanat, S.C., Biron, K.K., Furione, M., Bono, F., Palu, G. and Gerna, G., (1995), A three-nucleotide deletion in the UL97 open reading frame is responsible for the ganciclovir resistance of a human cytomegalovirus clinical isolate. J Virol, 69, 796–800.

    PubMed  CAS  Google Scholar 

  • Baldanti, F., Underwood, M.R., Stanat, S.C., Biron, K.K., Chou, S., Sarasini, A., Silini, E. and Gerna, G., (1996), Single amino acid changes in the DNA polymerase confer foscarnet resistance and slow-growth phenotype, while mutations in the UL97-encoded phosphotransferase confer ganciclovir resistance in three double-resistant human cytomegalovirus strains recovered from patients with AIDS. J Virol, 70, 1390–1395.

    PubMed  CAS  Google Scholar 

  • Baldanti, F., Underwood, M.R., Talarico, C.L., Simoncini, L., Sarasini, A., Biron, K.K. and Gerna, G., (1998), The cys607–>tyr change in the UL97 phosphotransferase confers ganciclovir resistance to two human cytomegalovirus strains recovered from two immunocompromised patients. Antimicrob Agents Chemother, 42, 444–446.

    PubMed  CAS  Google Scholar 

  • Balfour, H.H., Jr., (1999), Antiviral drugs. N Engl J Med, 340, 1255–1268.

    PubMed  CAS  Google Scholar 

  • Bendel, A.E., Gross, T.G., Woods, W.G., Edelman, C.K. and Balfour, H.H., Jr., (1993), Failure of foscarnet in disseminated herpes zoster. Lancet, 341, 1342.

    PubMed  CAS  Google Scholar 

  • Benz, C., Holz, G., Michel, D., Awerkiew, S., Dries, V., Stippel, D., Goeser, T. and Busch, D.H., (2003), Viral escape and T-cell immunity during ganciclovir treatment of cytomegalovirus infection: case report of a pancreatico-renal transplant recipient. Transplantation, 75, 724–727.

    PubMed  Google Scholar 

  • Bestman-Smith, J. and Boivin, G., (2002), Herpes simplex virus isolates with reduced adefovir susceptibility selected in vivo by foscarnet therapy. J Med Virol, 67, 88–91.

    PubMed  CAS  Google Scholar 

  • Bestman-Smith, J. and Boivin, G., (2003), Drug resistance patterns of recombinant herpes simplex virus DNA polymerase mutants generated with a set of overlapping cosmids and plasmids. J Virol, 77, 7820–7829.

    PubMed  CAS  Google Scholar 

  • Bestman-Smith, J., Schmit, I., Papadopoulou, B. and Boivin, G., (2001), Highly reliable heterologous system for evaluating resistance of clinical herpes simplex virus isolates to nucleoside analogues. J Virol, 75, 3105–3110.

    PubMed  CAS  Google Scholar 

  • Bhorade, S.M., Lurain, N.S., Jordan, A., Leischner, J., Villanueva, J., Durazo, R., Creech, S., Vigneswaran, W.T. and Garrity, E.R., (2002), Emergence of ganciclovir-resistant cytomegalovirus in lung transplant recipients. J Heart Lung Transplant, 21, 1274–1282.

    PubMed  Google Scholar 

  • Bidanset, D.J., Beadle, J.R., Wan, W.B., Hostetler, K.Y. and Kern, E.R., (2004), Oral activity of ether lipid ester prodrugs of cidofovir against experimental human cytomegalovirus infection. J Infect Dis, 190, 499–503.

    PubMed  CAS  Google Scholar 

  • Biron, K.K., Harvey, R.J., Chamberlain, S.C., Good, S.S., Smith, A.A., 3rd, Davis, M.G., Talarico, C.L., Miller, W.H., Ferris, R., Dornsife, R.E., Stanat, S.C., Drach, J.C., Townsend, L.B. and Koszalka, G.W., (2002), Potent and selective inhibition of human cytomegalovirus replication by 1263w94, a benzimidazole l-riboside with a unique mode of action. Antimicrob Agents Chemother, 46, 2365–2372.

    PubMed  CAS  Google Scholar 

  • Biron, K.K., Stanat, S.C., Sorrell, J.B., Fyfe, J.A., Keller, P.M., Lambe, C.U. and Nelson, D.J., (1985), Metabolic activation of the nucleoside analog 9-[(2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine in human diploid fibroblasts infected with human cytomegalovirus. Proc Natl Acad Sci USA, 82, 2473–2477.

    PubMed  CAS  Google Scholar 

  • Boeckh, M. and Boivin, G., (1998), Quantitation of cytomegalovirus: methodologic aspects and clinical applications. Clin Microbiol Rev, 11, 533–554.

    PubMed  CAS  Google Scholar 

  • Boeckh, M., Leisenring, W., Riddell, S.R., Bowden, R.A., Huang, M.L., Myerson, D., Stevens-Ayers, T., Flowers, M.E., Cunningham, T. and Corey, L., (2003), Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity. Blood, 101, 407–414.

    PubMed  CAS  Google Scholar 

  • Boivin, G., Chou, S., Quirk, M.R., Erice, A. and Jordan, M.C., (1996), Detection of ganciclovir resistance mutations and quantitation of cytomegalovirus (CMV) DNA in leukocytes of patients with fatal disseminated CMV disease. J Infect Dis, 173, 523–528.

    PubMed  CAS  Google Scholar 

  • Boivin, G., Edelman, C.K., Pedneault, L., Talarico, C.L., Biron, K.K. and Balfour, H.H.J., (1994), Phenotypic and genotypic characterization of acyclovir-resistant varicella-zoster viruses isolated from persons with AIDS. J Infect Dis, 170, 68–75.

    PubMed  CAS  Google Scholar 

  • Boivin, G., Erice, A., Crane, D.D., Dunn, D.L. and Balfour, H.H., Jr., (1993), Acyclovir susceptibilities of herpes simplex virus strains isolated from solid organ transplant recipients after acyclovir or ganciclovir prophylaxis. Antimicrob Agents Chemother, 37, 357–359.

    PubMed  CAS  Google Scholar 

  • Boivin, G., Gilbert, C., Gaudreau, A., Greenfield, I., Sudlow, R. and Roberts, N.A., (2001), Rate of emergence of cytomegalovirus (CMV) mutations in leukocytes of patients with acquired immunodeficiency syndrome who are receiving valganciclovir as induction and maintenance therapy for CMV retinitis. J Infect Dis, 184, 1598–1602.

    PubMed  CAS  Google Scholar 

  • Boivin, G., Goyette, N., Gilbert, C. and Covington, E., (2005a), Analysis of cytomegalovirus DNA polymerase (UL54) mutations in solid organ transplant patients receiving valganciclovir or ganciclovir prophylaxis. J Med Virol, 77, 425–429.

    CAS  Google Scholar 

  • Boivin, G., Goyette, N., Gilbert, C., Humar, A. and Covington, E., (2005b), Clinical impact of ganciclovir-resistant cytomegalovirus infections in solid organ transplant patients. Transpl Infect Dis, 6, 1–5.

    Google Scholar 

  • Boivin, G., Goyette, N., Gilbert, C., Roberts, N., Macey, K., Paya, C., Pescovitz, M.D., Humar, A., Dominguez, E., Washburn, K., Blumberg, E., Alexander, B., Freeman, R., Heaton, N. and Covington, E., (2004), Absence of cytomegalovirus-resistance mutations after valganciclovir prophylaxis, in a prospective multicenter study of solid-organ transplant recipients. J Infect Dis, 189, 1615–1618.

    PubMed  CAS  Google Scholar 

  • Boon, R.J., Bacon, T.H., Robey, H.L., Coleman, T.J., Connolly, A., Crosson, P. and Sacks, S.L., (2000), Antiviral susceptibilities of herpes simplex virus from immunocompetent subjects with recurrent herpes labialis: a UK-based survey. J Antimicrob Chemother, 46, 1051.

    PubMed  CAS  Google Scholar 

  • Chakrabarti, S., Pillay, D., Ratcliffe, D., Cane, P.A., Collingham, K.E. and Milligan, D.W., (2000), Resistance to antiviral drugs in herpes simplex virus infections among allogeneic stem cell transplant recipients: risk factors and prognostic significance. J Infect Dis, 181, 2055–2058.

    PubMed  CAS  Google Scholar 

  • Chatis, P.A. and Crumpacker, C.S., (1991), Analysis of the thymidine kinase gene from clinically isolated acyclovir-resistant herpes simplex viruses. Virology 180, 793–797.

    PubMed  CAS  Google Scholar 

  • Chatis, P.A., Miller, C.H., Schrager, L.E. and Crumpacker, C.S., (1989), Successful treatment with foscarnet of an acyclovir-resistant mucocutaneous infection with herpes simplex virus in a patient with acquired immunodeficiency syndrome. N Engl J Med, 320, 297–300.

    PubMed  CAS  Google Scholar 

  • Chen, Y., Scieux, C., Garrait, V., Socie, G., Rocha, V., Molina, J.M., Thouvenot, D., Morfin, F., Hocqueloux, L., Garderet, L., Esperou, H., Selimi, F., Devergie, A., Leleu, G., Aymard, M., Morinet, F., Gluckman, E. and Ribaud, P., (2000), Resistant herpes simplex virus type 1 infection: an emerging concern after allogeneic stem cell transplantation. Clin Infect Dis, 31, 927–935.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Chilukuri, S. and Rosen, T., (2003), Management of acyclovir-resistant herpes simplex virus. Dermatol Clin, 21, 311–320.

    PubMed  CAS  Google Scholar 

  • Chou, S., Erice, A., Jordan, M.C., Vercellotti, G.M., Michels, K.R., Talarico, C.L., Stanat, S.C. and Biron, K.K., (1995), Analysis of the UL97 phosphotransferase coding sequence in clinical cytomegalovirus isolates and identification of mutations conferring ganciclovir resistance. J Infect Dis, 171, 576–583.

    PubMed  CAS  Google Scholar 

  • Chou, S., Lurain, N.S., Thompson, K.D., Miner, R.C. and Drew, W.L., (2003), Viral DNA polymerase mutations associated with drug resistance in human cytomegalovirus. J Infect Dis, 188, 32–39.

    PubMed  CAS  Google Scholar 

  • Chou, S., Lurain, N.S., Weinberg, A., Cai, G.Y., Sharma, P.L. and Crumpacker, C.S., (1999), Interstrain variation in the human cytomegalovirus DNA polymerase sequence and its effect on genotypic diagnosis of antiviral drug resistance. Antimicrob Agents Chemother, 43, 1500–1502.

    PubMed  CAS  Google Scholar 

  • Chou, S., Marousek, G., Guentzel, S., Follansbee, S.E., Poscher, M.E., Lalezari, J.P., Miner, R.C. and Drew, W.L., (1997), Evolution of mutations conferring multidrug resistance during prophylaxis and therapy for cytomegalovirus disease. J Infect Dis, 176, 786–789.

    PubMed  CAS  Google Scholar 

  • Chou, S., Marousek, G., Parenti, D.M., Gordon, S.M., LaVoy, A.G., Ross, J.G., Miner, R.C. and Drew, W.L., (1998), Mutation in region III of the DNA polymerase gene conferring foscarnet resistance in cytomegalovirus isolates from 3 subjects receiving prolonged antiviral therapy. J Infect Dis, 178, 526–530.

    PubMed  CAS  Google Scholar 

  • Chou, S., Marousek, G.I., Senters, A.E., Davis, M.G. and Biron, K.K., (2004), Mutations in the human cytomegalovirus UL27 gene that confer resistance to maribavir. J Virol, 78, 7124–7130.

    PubMed  CAS  Google Scholar 

  • Chou, S. and Meichsner, C.L., (2000), A nine-codon deletion mutation in the cytomegalovirus UL97 phosphotransferase gene confers resistance to ganciclovir. Antimicrob Agents Chemother, 44, 183–185.

    PubMed  CAS  Google Scholar 

  • Chou, S., Waldemer, R.H., Senters, A.E., Michels, K.S., Kemble, G.W., Miner, R.C. and Drew, W.L., (2002), Cytomegalovirus UL97 phosphotransferase mutations that affect susceptibility to ganciclovir. J Infect Dis, 185, 162–169.

    PubMed  CAS  Google Scholar 

  • Chou, S., Van Wechel, L.C., Lichy, H.M. and Marousek, G.I., (2005), Phenotyping of cytomegalovirus drug resistance mutations by using recombinant viruses incorporating a reporter gene. Antimicrob Agents Chemother, 49, 2710–2715.

    PubMed  CAS  Google Scholar 

  • Chrisp, P. and Clissold, S.P., (1991), Foscarnet. A review of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with cytomegalovirus retinitis. Drugs, 41, 104–129.

    PubMed  CAS  Google Scholar 

  • Christophers, J., Clayton, J., Craske, J., Ward, R., Collins, P., Trowbridge, M. and Darby, G., (1998), Survey of resistance of herpes simplex virus to acyclovir in Northwest England. Antimicrob Agents Chemother, 42, 868–872.

    PubMed  CAS  Google Scholar 

  • Cihlar, T. and Chen, M.S., (1996), Identification of enzymes catalyzing two-step phosphorylation of cidofovir and the effect of cytomegalovirus infection on their activities in host cells. Mol Pharmacol, 50, 1502–1510.

    PubMed  CAS  Google Scholar 

  • Cihlar, T., Fuller, M. and Cherrington, J., (1998a), Characterization of drug resistance-associated mutations in the human cytomegalovirus DNA polymerase gene by using recombinant mutant viruses generated from overlapping DNA fragments. J Virol, 72, 5927–5936.

    CAS  Google Scholar 

  • Cihlar, T., Fuller, M.D., Mulato, A.S. and Cherrington, J.M., (1998b), A point mutation in the human cytomegalovirus DNA polymerase gene selected in vitro by cidofovir confers a slow replication phenotype in cell culture. Virology 248, 382–393.

    CAS  Google Scholar 

  • Coen, D.M., Kosz Vnenchak, M., Jacobson, J.G., Leib, D.A., Bogard, C.L., Schaffer, P.A., Tyler, K.L. and Knipe, D.M., (1989), Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate. Proc Natl Acad Sci USA, 86, 4736–4740.

    PubMed  CAS  Google Scholar 

  • Collins, P. and Ellis, M.N., (1993), Sensitivity monitoring of clinical isolates of herpes simplex virus to acyclovir. J Med Virol, Supplement 1, 58–66.

    Google Scholar 

  • Collins, P., Larder, B.A., Oliver, N.M., Kemp, S., Smith, I.W. and Darby, G., (1989), Characterization of a DNA polymerase mutant of herpes simplex virus from a severely immunocompromised patient receiving acyclovir. J Gen Virol, 70, 375–382.

    PubMed  CAS  Google Scholar 

  • Dankner, W.M., Scholl, D., Stanat, S.C., Martin, M., Sonke, R.L. and Spector, S.A., (1990), Rapid antiviral DNA–DNA hybridization assay for human cytomegalovirus. J Virol Meth, 28, 293–298.

    CAS  Google Scholar 

  • Danve-Szatanek, C., Aymard, M., Thouvenot, D., Morfin, F., Agius, G., Bertin, I., Billaudel, S., Chanzy, B., Coste-Burel, M., Finkielsztejn, L., Fleury, H., Hadou, T., Henquell, C., Lafeuille, H., Lafon, M.E., Le Faou, A., Legrand, M.C., Maille, L., Mengelle, C., Morand, P., Morinet, F., Nicand, E., Omar, S., Picard, B., Pozzetto, B., Puel, J., Raoult, D., Scieux, C., Segondy, M., Seigneurin, J.M., Teyssou, R. and Zandotti, C., (2004), Surveillance network for herpes simplex virus resistance to antiviral drugs: 3-year follow-up. J Clin Microbiol, 42, 242–249.

    PubMed  CAS  Google Scholar 

  • Darby, G., Larder, B.A. and Inglis, M.M., (1986), Evidence that the “active centre” of the herpes simplex virus thymidine kinase involves an interaction between three distinct regions of the polypeptide. J Gen Virol, 67, 753–758.

    CAS  Google Scholar 

  • De Clercq, E., (2004), Discovery and development of BVDU (brivudin) as a therapeutic for the treatment of herpes zoster. Biochem Pharmacol, 68, 2301–2315.

    PubMed  Google Scholar 

  • DeJesus, E., Wald, A., Warren, T., Schacker, T.W., Trottier, S., Shahmanesh, M., Hill, J.L. and Brennan, C.A., (2003), Valacyclovir for the suppression of recurrent genital herpes in human immunodeficiency virus-infected subjects. J Infect Dis, 188, 1009–1016.

    PubMed  CAS  Google Scholar 

  • Drew, W.L., (2003), Cytomegalovirus disease in the highly active antiretroviral therapy era. Curr Infect Dis Rep, 5, 257–265.

    PubMed  Google Scholar 

  • Drew, W.L., Anderson, R., Lang, W., Miner, R.C., Davis, G. and Lalezari, J., (1995), Failure of high-dose oral acyclovir to suppress CMV viruria or induce ganciclovir-resistant CMV in HIV antibody positive patients. J Acquir Immune Defic Syndr Hum Retrovirol, 8, 289–291.

    PubMed  CAS  Google Scholar 

  • Drew, W.L., Miner, R.C., Busch, D.F., Follansbee, S.E., Gullett, J., Mehalko, S.G., Gordon, S.M., Owen, W.F., Jr, Matthews, T.R. and Buhles, W.C., (1991), Prevalence of resistance in patients receiving ganciclovir for serious cytomegalovirus infection. J Infect Dis, 163, 716–719.

    PubMed  CAS  Google Scholar 

  • Drew, W.L., Paya, C.V. and Emery, V., (2001), Cytomegalovirus (CMV) resistance to antivirals. Am J Transplant, 1, 307–312.

    PubMed  CAS  Google Scholar 

  • Drew, W.L., Stempien, M.J., Andrews, J., Shadman, A., Tan, S.J., Miner, R. and Buhles, W., (1999), Cytomegalovirus (CMV) resistance in patients with CMV retinitis and AIDS treated with oral or intravenous ganciclovir. J Infect Dis, 179, 1352–1355.

    PubMed  CAS  Google Scholar 

  • Duan, J., Liuzzi, M., Paris, W., Lambert, M., Lawetz, C., Moss, N., Jaramillo, J., Gauthier, J., Deziel, R. and Cordingley, M.G., (1998), Antiviral activity of a selective ribonucleotide reductase inhibitor against acyclovir-resistant herpes simplex virus type 1 in vivo. Antimicrob Agents Chemother, 42, 1629–1635.

    PubMed  CAS  Google Scholar 

  • Eckle, T., Prix, L., Jahn, G., Klingebiel, T., Handgretinger, R., Selle, B. and Hamprecht, K., (2000), Drug-resistant human cytomegalovirus infection in children after allogeneic stem cell transplantation may have different clinical outcomes. Blood, 96, 3286–3289.

    PubMed  CAS  Google Scholar 

  • Emery, V.C. and Hassan-Walker, A.F., (2002), Focus on new drugs in development against human cytomegalovirus. Drugs, 62, 1853–1858.

    PubMed  CAS  Google Scholar 

  • Engel, J.P., Englund, J.A., Fletcher, C.V. and Hill, E.L., (1990), Treatment of resistant herpes simplex virus with continuous-infusion acyclovir. JAMA, 263, 1662–1664.

    PubMed  CAS  Google Scholar 

  • Englund, J.A., Zimmerman, M.E., Swierkosz, E.M., Goodman, J.L., Scholl, D.R. and Balfour, H.H., (1990), Herpes simplex virus resistant to acyclovir: a study in a tertiary care center. Ann Intern Med, 112, 416–422.

    PubMed  CAS  Google Scholar 

  • Erice, A., Borrell, N., Li, W., Miller, W.J. and Balfour, H.H., Jr., (1998), Ganciclovir susceptibilities and analysis of UL97 region in cytomegalovirus (CMV) isolates from bone marrow recipients with CMV disease after antiviral prophylaxis. J Infect Dis, 178, 531–534.

    PubMed  CAS  Google Scholar 

  • Erice, A., Gil-Roda, C., Perez, J.L., Balfour, H.H., Sannerud, K.J., Hanson, M.N., Boivin, G. and Chou, S., (1997), Antiviral susceptibilities and analysis of UL97 and DNA polymerase sequences of clinical cytomegalovirus isolates from immunocompromised patients. J Infect Dis, 175, 1087–1092.

    PubMed  CAS  Google Scholar 

  • Erlich, K.S., Jacobson, M.A., Koehler, J.E., Follansbee, S.E., Drennan, D.P., Gooze, L., Safrin, S. and Mills, J., (1989b), Foscarnet therapy for severe acyclovir-resistant herpes simplex virus type-2 infections in patients with the acquired immunodeficiency syndrome (AIDS). An uncontrolled trial. Ann Intern Med, 110, 710–713.

    CAS  Google Scholar 

  • Erlich, K.E., Mills, J., Chatis, P., Mertz, G.J., Busch, D.F., Follansbee, S.E., Grant, R.M. and Crumpacker, C.S., (1989a), Acyclovir-resistant herpes simplex virus infections in patients with the acquired immunodeficiency syndrome. N Engl J Med, 320, 293–296.

    CAS  Google Scholar 

  • Fife, K.H., Crumpacker, C.S., Mertz, G.J., Hill, E.L. and Boone, G.S., (1994), Recurrence and resistance patterns of herpes simplex virus following cessation of > or = 6 years of chronic suppression with acyclovir. J Infect Dis, 169, 1338–1341.

    PubMed  CAS  Google Scholar 

  • Fillet, A.M., Auray, L., Alain, S., Gourlain, K., Imbert, B.M., Najioullah, F., Champier, G., Gouarin, S., Carquin, J., Houhou, N., Garrigue, I., Ducancelle, A., Thouvenot, D. and Mazeron, M.C., (2004), Natural polymorphism of cytomegalovirus DNA polymerase lies in two nonconserved regions located between domains delta-C and II and between domains III and I. Antimicrob Agents Chemother, 48, 1865–1868.

    PubMed  CAS  Google Scholar 

  • Fillet, A.M., Dumont, B., Caumes, E., Visse, B., Agut, H., Bricaire, F. and Huraux, J.M., (1998), Acyclovir-resistant varicella-zoster virus: phenotypic and genetic characterization. J Med Virol, 55, 250–254.

    PubMed  CAS  Google Scholar 

  • Fillet, A.M., Visse, B., Caumes, E., Dumont, B., Gentilini, M. and Huraux, J.M., (1995), Foscarnet-resistant multidermatomal zoster in a patient with AIDS. Clin Infect Dis, 21, 1348–1349.

    PubMed  CAS  Google Scholar 

  • Fyfe, J.A., Keller, P.M., Furman, P.A., Miller, R.L. and Elion, G.B., (1978), Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl)guanine. J Biol Chem, 253, 8721–8727.

    PubMed  CAS  Google Scholar 

  • Gaudreau, A., Hill, E., Balfour, H.H., Jr, Erice, A. and Boivin, G., (1998), Phenotypic and genotypic characterization of acyclovir-resistant herpes simplex viruses from immunocompromised patients. J Infect Dis, 178, 297–303.

    PubMed  CAS  Google Scholar 

  • Gerna, G., Baldanti, F., Zavattoni, M., Sarasini, A., Percivalle, E. and Revello, M.G., (1992), Monitoring of ganciclovir sensitivity of multiple human cytomegalovirus strains coinfecting blood of an AIDS patient by an immediate–early antigen plaque assay. Antiviral Res, 19, 333–345.

    PubMed  CAS  Google Scholar 

  • Gerna, G., Sarasini, A., Lilleri, D., Percivalle, E., Torsellini, M., Baldanti, F. and Revello, M.G., (2003), In vitro model for the study of the dissociation of increasing antigenemia and decreasing DNAemia and viremia during treatment of human cytomegalovirus infection with ganciclovir in transplant recipients. J Infect Dis, 188, 1639–1647.

    PubMed  CAS  Google Scholar 

  • Gilbert, C., Bestman-Smith, J. and Boivin, G., (2002), Resistance of herpesviruses to antiviral drugs: clinical impacts and molecular mechanisms. Drug Resist Updat, 5, 88–114.

    PubMed  CAS  Google Scholar 

  • Gilbert, C. and Boivin, G., (2003), Discordant phenotypes and genotypes of cytomegalovirus (CMV) in patients with AIDS and relapsing CMV retinitis. AIDS, 17, 337–341.

    PubMed  CAS  Google Scholar 

  • Gilbert, C. and Boivin, G., (2005a), New reporter cell line to evaluate the sequential emergence of multiple human cytomegalovirus mutations during in vitro drug exposure. Antimicrob Agents Chemother, 49, 4860–4866.

    CAS  Google Scholar 

  • Gilbert, C. and Boivin, G., (2005b), Human cytomegalovirus resistance to antiviral drugs. Antimicrob Agents Chemother, 49, 873–883.

    CAS  Google Scholar 

  • Gilbert, C., Roy, J., Belanger, R., Delage, R., Beliveau, C., Demers, C. and Boivin, G., (2001), Lack of emergence of cytomegalovirus UL97 mutations conferring ganciclovir (GCV) resistance following preemptive GCV therapy in allogeneic stem cell transplant recipients. Antimicrob Agents Chemother, 45, 3669–3671.

    PubMed  CAS  Google Scholar 

  • Gupta, R., Hill, E.L., McClernon, D., Davis, G., Selke, S., Corey, L. and Wald, A., (2005), Acyclovir sensitivity of sequential herpes simplex virus type 2 isolates from the genital mucosa of immunocompetent women. J Infect Dis, 192, 1102–1107.

    PubMed  CAS  Google Scholar 

  • Hamprecht, K., Eckle, T., Prix, L., Faul, C., Einsele, H. and Jahn, G., (2003), Ganciclovir-resistant cytomegalovirus disease after allogeneic stem cell transplantation: pitfalls of phenotypic diagnosis by in vitro selection of an UL97 mutant strain. J Infect Dis, 187, 139–143.

    PubMed  CAS  Google Scholar 

  • Hanson, M.N., Preheim, L.C., Chou, S., Talarico, C.L., Biron, K.K. and Erice, A., (1995), Novel mutation in the UL97 gene of a clinical cytomegalovirus strain conferring resistance to ganciclovir. Antimicrob Agents Chemother, 39, 1204–1205.

    PubMed  CAS  Google Scholar 

  • Hill, E.L., Hunter, G.A. and Ellis, M.N., (1991), In vitro and in vivo characterization of herpes simplex virus clinical isolates recovered from patients infected with human immunodeficiency virus. Antimicrob Agents Chemother, 35, 2322–2328.

    PubMed  CAS  Google Scholar 

  • Hu, H., Jabs, D.A., Forman, M.S., Martin, B.K., Dunn, J.P., Weinberg, D.V. and Davis, J.L., (2002), Comparison of cytomegalovirus (CMV) UL97 gene sequences in the blood and vitreous of patients with acquired immunodeficiency syndrome and CMV retinitis. J Infect Dis, 185, 861–867.

    PubMed  CAS  Google Scholar 

  • Humar, A., Kumar, D., Preiksaitis, J., Boivin, G., Siegal, D., Fenton, J., Jackson, K., Nia, S. and Lien, D., (2005), A trial of valganciclovir prophylaxis for cytomegalovirus prevention in lung transplant recipients. Am J Transplant, 5, 1462–1468.

    PubMed  CAS  Google Scholar 

  • Hwang, C.B., Ruffner, K.L. and Coen, D.M., (1992), A point mutation within a distinct conserved region of the herpes simplex virus DNA polymerase gene confers drug resistance. J Virol, 66, 1774–1776.

    PubMed  CAS  Google Scholar 

  • Jabs, D.A., Enger, C., Dunn, J.P. and Forman, M., (1998a), Cytomegalovirus retinitis and viral resistance: ganciclovir resistance. J Infect Dis, 177, 770–773.

    CAS  Google Scholar 

  • Jabs, D.A., Enger, C., Forman, M. and Dunn, J.P., (1998b), Incidence of foscarnet resistance and cidofovir resistance in patients treated for cytomegalovirus retinitis. The Cytomegalovirus Retinitis and Viral Resistance Study Group. Antimicrob Agents Chemother, 42, 2240–2244.

    CAS  Google Scholar 

  • Jabs, D.A., Martin, B.K., Forman, M.S., Dunn, J.P., Davis, J.L., Weinberg, D.V., Biron, K.K. and Baldanti, F., (2001a), Mutations conferring ganciclovir resistance in a cohort of patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis. J Infect Dis, 183, 333–337.

    CAS  Google Scholar 

  • Jabs, D.A., Martin, B.K., Forman, M.S., Dunn, J.P., Davis, J.L., Weinberg, D.V., Biron, K.K., Baldanti, F. and Hu, H., (2001b), Longitudinal observations on mutations conferring ganciclovir resistance in patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis: The Cytomegalovirus and Viral Resistance Study Group report number 8. Am J Ophthalmol, 132, 700–710.

    CAS  Google Scholar 

  • Jacobson, M.A., Berger, T.G., Fikrig, S., Becherer, P., Moohr, J.W., Stanat, S.C. and Biron, K.K., (1990), Acyclovir-resistant varicella zoster virus infection after chronic oral acyclovir therapy in patients with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med, 112, 187–191.

    PubMed  CAS  Google Scholar 

  • Kessler, H.A., Hurwitz, S., Farthing, C., Benson, C.A., Feinberg, J., Kuritzkes, D.R., Bailey, T.C., Safrin, S., Steigbigel, R.T., Cheeseman, S.H., McKinley, G.F., Wettlaufer, B., Owens, S., Nevin, T. and Korvick, J.A., (1996), Pilot study of topical trifluridine for the treatment of acyclovir-resistant mucocutaneous herpes simplex disease in patients with AIDS (ACTG 172). aIDS Clinical Trials Group. J Acquir Immune Defic Syndr Hum Retrovirol, 12, 147–152.

    PubMed  CAS  Google Scholar 

  • Kesson, A., Zeng, F., Cunningham, A. and Rawlinson, W., (1998), The use of flow cytometry to detect antiviral resistance in human cytomegalovirus. J Virol Meth, 71, 177–186.

    CAS  Google Scholar 

  • Komazin, G., Ptak, R.G., Emmer, B.T., Townsend, L.B. and Drach, J.C., (2003), Resistance of human cytomegalovirus to the benzimidazole l-ribonucleoside maribavir maps to UL27. J Virol, 77, 11499–11506.

    PubMed  CAS  Google Scholar 

  • Kopp, T., Geusau, A., Rieger, A. and Stingl, G., (2002), Successful treatment of an aciclovir-resistant herpes simplex type 2 infection with cidofovir in an AIDS patient. Br J Dermatol, 147, 134–138.

    PubMed  CAS  Google Scholar 

  • Kost, R.G., Hill, E.L., Tigges, M. and Straus, S.E., (1993), Brief report: recurrent acyclovir-resistant genital herpes in an immunocompetent patient. N Engl J Med, 329, 1777–1782.

    PubMed  CAS  Google Scholar 

  • Koszalka, G.W., Johnson, N.W., Good, S.S., Boyd, L., Chamberlain, S.C., Townsend, L.B., Drach, J.C. and Biron, K.K., (2002), Preclinical and toxicology studies of 1263w94, a potent and selective inhibitor of human cytomegalovirus replication. Antimicrob Agents Chemother, 46, 2373–2380.

    PubMed  CAS  Google Scholar 

  • Kriesel, J.D., Spruance, S.L., Prichard, M., Parker, J.N. and Kern, E.R., (2005), Recurrent antiviral-resistant genital herpes in an immunocompetent patient. J Infect Dis, 192, 156–161.

    PubMed  Google Scholar 

  • Krosky, P.M., Baek, M.C. and Coen, D.M., (2003), The human cytomegalovirus UL97 protein kinase, an antiviral drug target, is required at the stage of nuclear egress. J Virol, 77, 905–914.

    PubMed  CAS  Google Scholar 

  • Kruger, R.M., Shannon, W.D., Arens, M.Q., Lynch, J.P., Storch, G.A. and Trulock, E.P., (1999), The impact of ganciclovir-resistant cytomegalovirus infection after lung transplantation. Transplantation, 68, 1272–1279.

    PubMed  CAS  Google Scholar 

  • Lalezari, J., Schacker, T., Feinberg, J., Gathe, J., Lee, S., Cheung, T., Kramer, F., Kessler, H., Corey, L., Drew, W.L., Boggs, J., McGuire, B., Jaffe, H.S. and Safrin, S., (1997), A randomized, double-blind, placebo-controlled trial of cidofovir gel for the treatment of acyclovir-unresponsive mucocutaneous herpes simplex virus infection in patients with AIDS. J Infect Dis, 176, 892–898.

    PubMed  CAS  Google Scholar 

  • Lalezari, J.P., Aberg, J.A., Wang, L.H., Wire, M.B., Miner, R., Snowden, W., Talarico, C.L., Shaw, S., Jacobson, M.A. and Drew, W.L., (2002), Phase I dose escalation trial evaluating the pharmacokinetics, anti-human cytomegalovirus (HCMV) activity, and safety of 1263w94 in human immunodeficiency virus-infected men with asymptomatic HCMV shedding. Antimicrob Agents Chemother, 46, 2969–2976.

    PubMed  CAS  Google Scholar 

  • Lalezari, J.P., Drew, W.L., Glutzer, E., Miner, D., Safrin, S., Owen, W.F., Jr, Davidson, J.M., Fisher, P.E. and Jaffe, H.S., (1994), Treatment with intravenous (s)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]-cytosine of acyclovir-resistant mucocutaneous infection with herpes simplex virus in a patient with AIDS. J Infect Dis, 170, 570–572.

    PubMed  CAS  Google Scholar 

  • Landry, M.L., Stanat, S., Biron, K., Brambilla, D., Britt, W., Jokela, J., Chou, S., Drew, W.L., Erice, A., Gilliam, B., Lurain, N., Manischewitz, J., Miner, R., Nokta, M., Reichelderfer, P., Spector, S., Weinberg, A., Yen-Lieberman, B. and Crumpacker, C., (2000), A standardized plaque reduction assay for determination of drug susceptibilities of cytomegalovirus clinical isolates. Antimicrob Agents Chemother, 44, 688–692.

    PubMed  CAS  Google Scholar 

  • Langston, A.A., Redei, I., Caliendo, A.M., Somani, J., Hutcherson, D., Lonial, S., Bucur, S., Cherry, J., Allen, A. and Waller, E.K., (2002), Development of drug-resistant herpes simplex virus infection after haploidentical hematopoietic progenitor cell transplantation. Blood, 99, 1085–1088.

    PubMed  CAS  Google Scholar 

  • Levin, M.J., Bacon, T.H. and Leary, J.J., (2004), Resistance of herpes simplex virus infections to nucleoside analogues in HIV-infected patients. Clin Infect Dis, 39 (Suppl 5), S248–S257.

    PubMed  CAS  Google Scholar 

  • Limaye, A.P., (2002), Ganciclovir-resistant cytomegalovirus in organ transplant recipients. Clin Infect Dis, 35, 866–872.

    PubMed  CAS  Google Scholar 

  • Limaye, A.P., Corey, L., Koelle, D.M., Davis, C.L. and Boeckh, M., (2000), Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants. Lancet, 356, 645–649.

    PubMed  CAS  Google Scholar 

  • Limaye, A.P., Raghu, G., Koelle, D.M., Ferrenberg, J., Huang, M.L. and Boeckh, M., (2002), High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving preemptive therapy. J Infect Dis, 185, 20–27.

    PubMed  CAS  Google Scholar 

  • Liu, W., Kuppermann, B.D., Martin, D.F., Wolitz, R.A. and Margolis, T.P., (1998), Mutations in the cytomegalovirus UL97 gene associated with ganciclovir-resistant retinitis. J Infect Dis, 177, 1176–1181.

    PubMed  CAS  Google Scholar 

  • Liuzzi, M., Deziel, R., Moss, N., Beaulieu, P., Bonneau, A.M., Bousquet, C., Chafouleas, J.G., Garneau, M., Jaramillo, J., Krogsrud, R.L., Lagacè, L., McCollum, R.S., Nawoot, S. and Guindon, Y., (1994), A potent peptidomimetic inhibitor of HSV ribonucleotide reductase with antiviral activity in vivo. Nature, 372, 695–698.

    PubMed  CAS  Google Scholar 

  • Lowance, D., Neumayer, H.H., Legendre, C.M., Squifflet, J.P., Kovarik, J., Brennan, P.J., Norman, D., Mendez, R., Keating, M.R., Coggon, G.L., Crisp, A. and Lee, I.C., (1999), Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. N Engl J Med, 340, 1462–1470.

    PubMed  CAS  Google Scholar 

  • Lurain, N.S., Bhorade, S.M., Pursell, K.J., Avery, R.K., Yeldandi, V.V., Isada, C.M., Robert, E.S., Kohn, D.J., Arens, M.Q., Garrity, E.R., Taege, A.J., Mullen, M.G., Todd, K.M., Bremer, J.W. and Yen-Lieberman, B., (2002), Analysis and characterization of antiviral drug-resistant cytomegalovirus isolates from solid organ transplant recipients. J Infect Dis, 186, 760–768.

    PubMed  CAS  Google Scholar 

  • Lurain, N.S., Weinberg, A., Crumpacker, C.S. and Chou, S., (2001), Sequencing of cytomegalovirus UL97 gene for genotypic antiviral resistance testing. Antimicrob Agents Chemother, 45, 2775–2780.

    PubMed  CAS  Google Scholar 

  • Martin, J.L., Ellis, M.N., Keller, P.M., Biron, K.K., Lehrman, S.N., Barry, D.W. and Furman, P.A., (1985), Plaque autoradiography assay for the detection and quantification of thymidine kinase-deficient and thymidine kinase-altered mutants of herpes simplex virus in clinical isolates. Antimicrob Agents Chemother, 28, 181–187.

    PubMed  CAS  Google Scholar 

  • McSharry, J.J., McDonough, A., Olson, B., Hallenberger, S., Reefschlaeger, J., Bender, W. and Drusano, G.L., (2001), Susceptibilities of human cytomegalovirus clinical isolates to BAY38-4766, BAY43-9695, and ganciclovir. Antimicrob Agents Chemother, 45, 2925–2927.

    PubMed  CAS  Google Scholar 

  • McSharry, J.M., Lurain, N.S., Drusano, G.L., Landay, A., Manischewitz, J., Nokta, M., O’Gorman, M., Shapiro, H.M., Weinberg, A., Reichelderfer, P. and Crumpacker, C., (1998), Flow cytometric determination of ganciclovir susceptibilities of human cytomegalovirus clinical isolates. J Clin Microbiol, 36, 958–964.

    PubMed  CAS  Google Scholar 

  • Mertz, G.J., Jones, C.C., Mills, J., Fife, K.H., Lemon, S.M., Stapleton, J.T., Hill, E.L. and Davis, L.G., (1988), Long-term acyclovir suppression of frequently recurring genital herpes simplex virus infection. A multicenter double-blind trial. JAMA, 260, 201–206.

    PubMed  CAS  Google Scholar 

  • Michel, D., Hohn, S., Haller, T., Jun, D. and Mertens, T., (2001), Aciclovir selects for ganciclovir-cross-resistance of human cytomegalovirus in vitro that is only in part explained by known mutations in the UL97 protein. J Med Virol, 65, 70–76.

    PubMed  CAS  Google Scholar 

  • Michel, D. and Mertens, T., (2004), The UL97 protein kinase of human cytomegalovirus and homologues in other herpesviruses: impact on virus and host. Biochim Biophys Acta, 1697, 169–180.

    PubMed  CAS  Google Scholar 

  • Morfin, F., Souillet, G., Bilger, K., Ooka, T., Aymard, M. and Thouvenot, D., (2000a), Genetic characterization of thymidine kinase from acyclovir-resistant and susceptible herpes simplex virus type 1 isolated from bone marrow transplant recipients. J Infect Dis, 182, 290–293.

    CAS  Google Scholar 

  • Morfin, F. and Thouvenot, D., (2003), Herpes simplex virus resistance to antiviral drugs. J Clin Virol, 26, 29–37.

    PubMed  CAS  Google Scholar 

  • Morfin, F., Thouvenot, D., Aymard, M. and Souillet, G., (2000b), Reactivation of acyclovir-resistant thymidine kinase-deficient herpes simplex virus harbouring single base insertion within a 7 Gs homopolymer repeat of the thymidine kinase gene. J Med Virol, 62, 247–250.

    CAS  Google Scholar 

  • Morfin, F., Thouvenot, D., De Turenne-Tessier, M., Lina, B., Aymard, M. and Ooka, T., (1999), Phenotypic and genetic characterization of thymidine kinase from clinical strains of varicella-zoster virus resistant to acyclovir. Antimicrob Agents Chemother, 43, 2412–2416.

    PubMed  CAS  Google Scholar 

  • Mousavi-Jazi, M., Schloss, L., Drew, W.L., Linde, A., Miner, R.C., Harmenberg, J., Wahren, B. and Brytting, M., (2001), Variations in the cytomegalovirus DNA polymerase and phosphotransferase genes in relation to foscarnet and ganciclovir sensitivity. J Clin Virol, 23, 1–15.

    PubMed  CAS  Google Scholar 

  • Mulamba, G.B., Hu, A., Azad, R.F., Anderson, K.P. and Coen, D.M., (1998), Human cytomegalovirus mutant with sequence-dependent resistance to the phosphorothioate oligonucleotide fomivirsen (ISIS 2922). Antimicrob Agents Chemother, 42, 971–973.

    PubMed  CAS  Google Scholar 

  • Mylonakis, E., Kallas, W.M. and Fishman, J.A., (2002), Combination antiviral therapy for ganciclovir-resistant cytomegalovirus infection in solid-organ transplant recipients. Clin Infect Dis, 34, 1337–1341.

    PubMed  CAS  Google Scholar 

  • Nguyen, Q., Champlin, R., Giralt, S., Rolston, K., Raad, I., Jacobson, K., Ippoliti, C., Hecht, D., Tarrand, J., Luna, M. and Whimbey, E., (1999), Late cytomegalovirus pneumonia in adult allogeneic blood and marrow transplant recipients. Clin Infect Dis, 28, 618–623.

    PubMed  CAS  Google Scholar 

  • Nichols, W. and Boeckh, M., (2001), Cytomegalovirus infections. Curr Treat Options Infect Dis, 3, 78–91.

    Google Scholar 

  • Nichols, W.G., Corey, L., Gooley, T., Drew, W.L., Miner, R., Huang, M., Davis, C. and Boeckh, M., (2001), Rising pp65 antigenemia during preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes. Blood, 97, 867–874.

    PubMed  CAS  Google Scholar 

  • Paya, C., Humar, A., Dominguez, E., Washburn, K., Blumberg, E., Alexander, B., Freeman, R., Heaton, N. and Pescovitz, M.D., (2004), Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant, 4, 611–620.

    PubMed  CAS  Google Scholar 

  • Paya, C.V., Wilson, J.A., Espy, M.J., Sia, I.G., DeBernardi, M.J., Smith, T.F., Patel, R., Jenkins, G., Harmsen, W.S., Vanness, D.J. and Wiesner, R.H., (2002), Preemptive use of oral ganciclovir to prevent cytomegalovirus infection in liver transplant patients: a randomized, placebo-controlled trial. J Infect Dis, 185, 854–860.

    PubMed  CAS  Google Scholar 

  • Pescovitz, M.D., Rabkin, J., Merion, R.M., Paya, C.V., Pirsch, J., Freeman, R.B., O’Grady, J., Robinson, C., To, Z., Wren, K., Banken, L., Buhles, W. and Brown, F., (2000), Valganciclovir results in improved oral absorption of ganciclovir in liver transplant recipients. Antimicrob Agents Chemother, 44, 2811–2815.

    PubMed  CAS  Google Scholar 

  • Razonable, R.R., Rivero, A., Rodriguez, A., Wilson, J., Daniels, J., Jenkins, G., Larson, T., Hellinger, W.C., Spivey, J.R. and Paya, C.V., (2001), Allograft rejection predicts the occurrence of late-onset cytomegalovirus (CMV) disease among CMV-mismatched solid organ transplant patients receiving prophylaxis with oral ganciclovir. J Infect Dis, 184, 1461–1464.

    PubMed  CAS  Google Scholar 

  • Reefschlaeger, J., Bender, W., Hallenberger, S., Weber, O., Eckenberg, P., Goldmann, S., Haerter, M., Buerger, I., Trappe, J., Herrington, J.A., Haebich, D. and Ruebsamen-Waigmann, H., (2001), Novel non-nucleoside inhibitors of cytomegaloviruses (BAY 38-4766): in vitro and in vivo antiviral activity and mechanism of action. J Antimicrob Chemother, 48, 757–767.

    PubMed  CAS  Google Scholar 

  • Reyes, M., Shaik, N.S., Graber, J.M., Nisenbaum, R., Wetherall, N.T., Fukuda, K. and Reeves, W.C., (2003), Acyclovir-resistant genital herpes among persons attending sexually transmitted disease and human immunodeficiency virus clinics. Arch Intern Med, 163, 76–80.

    PubMed  Google Scholar 

  • Safrin, S., Ashley, R., Houlihan, C., Cusick, P.S. and Mills, J., (1991a), Clinical and serologic features of herpes simplex virus infection in patients with AIDS. AIDS, 5, 1107–1110.

    CAS  Google Scholar 

  • Safrin, S., Assaykeen, T., Follansbee, S. and Mills, J., (1990), Foscarnet therapy for acyclovir-resistant mucocutaneous herpes simplex virus infection in 26 AIDS patients: preliminary data. J Infect Dis, 161, 1078–1084.

    PubMed  CAS  Google Scholar 

  • Safrin, S., Berger, T.G., Gilson, I., Wolfe, P.R., Wofsy, C.B., Mills, J. and Biron, K.K., (1991b), Foscarnet therapy in five patients with AIDS and acyclovir-resistant varicella-zoster virus infection. Ann Intern Med, 115, 19–21.

    CAS  Google Scholar 

  • Safrin, S., Crumpacker, C., Chatis, P., Davis, R., Hafner, R., Rush, J., Kessler, H.A., Landry, B. and Mills, J., (1991c), A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome. N Engl J Med, 325, 551–555.

    CAS  Google Scholar 

  • Safrin, S., Kemmerly, S., Plotkin, B., Smith, T., Weissbach, N., De Veranez, D., Phan, L.D. and Cohn, D., (1994), Foscarnet-resistant herpes simplex virus infection in patients with AIDS. J Infect Dis, 169, 193–196.

    PubMed  CAS  Google Scholar 

  • Sahli, R., Andrei, G., Estrade, C., Snoeck, R. and Meylan, P.R., (2000), A rapid phenotypic assay for detection of acyclovir-resistant varicella-zoster virus with mutations in the thymidine kinase open reading frame. Antimicrob Agents Chemother, 44, 873–878.

    PubMed  CAS  Google Scholar 

  • Saint-Leger, E., Caumes, E., Breton, G., Douard, D., Saiag, P., Huraux, J.M., Bricaire, F., Agut, H. and Fillet, A.M., (2001), Clinical and virologic characterization of acyclovir-resistant varicella-zoster viruses isolated from 11 patients with acquired immunodeficiency syndrome. Clin Infect Dis, 33, 2061–2067.

    PubMed  CAS  Google Scholar 

  • Sarisky, R.T., Crosson, P., Cano, R., Quail, M.R., Nguyen, T.T., Wittrock, R.J., Bacon, T.H., Sacks, S.L., Caspers-Velu, L., Hodinka, R.L. and Leary, J.J., (2002), Comparison of methods for identifying resistant herpes simplex virus and measuring antiviral susceptibility. J Clin Virol, 23, 191–200.

    PubMed  CAS  Google Scholar 

  • Sasadeusz, J.J. and Sacks, S.L., (1996), Spontaneous reactivation of thymidine kinase-deficient, acyclovir-resistant type 2 herpes simplex virus: masked heterogeneity or reversion? J Infect Dis, 174, 476–482.

    PubMed  CAS  Google Scholar 

  • Schmit, I. and Boivin, G., (1999), Characterization of the DNA polymerase and thymidine kinase genes of herpes simplex virus isolates from AIDS patients in whom acyclovir and foscarnet therapy sequentially failed. J Infect Dis, 180, 487–490.

    PubMed  CAS  Google Scholar 

  • Smith, I.L., Cherrington, J.M., Jiles, R.E., Fuller, M.D., Freeman, W.R. and Spector, S.A., (1997), High-level resistance of cytomegalovirus to ganciclovir is associated with alterations in both the UL97 and DNA polymerase genes. J Infect Dis, 176, 69–77.

    PubMed  CAS  Google Scholar 

  • Smith, I.L., Shinkai, M., Freeman, W.R. and Spector, S.A., (1996), Polyradiculopathy associated with ganciclovir-resistant cytomegalovirus in an AIDS patient: phenotypic and genotypic characterization of sequential virus isolates. J Infect Dis, 173, 1481–1484.

    PubMed  CAS  Google Scholar 

  • Smith, I.L., Taskintuna, I., Rahhal, F.M., Powell, H.C., Ai, E., Mueller, A.J., Spector, S.A. and Freeman, W.R., (1998), Clinical failure of CMV retinitis with intravitreal cidofovir is associated with antiviral resistance. Arch Ophthalmol, 116, 178–185.

    PubMed  CAS  Google Scholar 

  • Snoeck, R, Andrei, G., Gerard, M., Silverman, A., Hedderman, A., Balzarini, J., Sadzot-Delvaux, C., Tricot, G., Clumeck, N. and De Clercq, E., (1994), Successful treatment of progressive mucocutaneous infection due to acyclovir- and foscarnet-resistant herpes simplex virus with (s)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC). Clin Infect Dis, 18, 570–578.

    PubMed  CAS  Google Scholar 

  • SOCA (Studies of Ocular Complications of AIDS Research Group and AIDS Clinical Trials Group), (1996), Combination foscarnet and ganciclovir therapy vs monotherapy for the treatment of relapsed cytomegalovirus retinitis in patients with AIDS. Arch Ophtalmol, 114, 23–33.

    Google Scholar 

  • Springer, K.L., Chou, S., Li, S., Giller, R.H., Quinones, R., Shira, J.E. and Weinberg, A., (2005), How evolution of mutations conferring drug resistance affects viral dynamics and clinical outcomes of cytomegalovirus-infected hematopoietic cell transplant recipients. J Clin Microbiol, 43, 208–213.

    PubMed  CAS  Google Scholar 

  • Sullivan, V., Talarico, C.L., Stanat, S.C., Davis, M., Coen, D.M. and Biron, K.K., (1992), A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells. Nature, 359, 85.

    PubMed  CAS  Google Scholar 

  • Swetter, S.M., Hill, E.L., Kern, E.R., Koelle, D.M., Posavard, C.M., Lawrence, W. and Safrin, S., (1998), Chronic vulvar ulceration in an immunocompetent woman due to acyclovir-resistant, thymidine kinase-deficient herpes simplex virus. J Infect Dis, 177, 543–550.

    PubMed  CAS  Google Scholar 

  • Tatarowicz, W.A., Lurain, N.S. and Thompson, K.D., (1991), In situ ELISA for the evaluation of antiviral compounds effective against human cytomegalovirus. J Virol Meth, 35, 207–215.

    CAS  Google Scholar 

  • Telenti, A. and Smith, T.F., (1989), Screening with a shell vial assay for antiviral activity against cytomegalovirus. Diagn Microbiol Infect Dis, 12, 5–8.

    PubMed  CAS  Google Scholar 

  • Tenser, R.B., Hay, K.A. and Edris, W.A., (1989), Latency-associated transcript but not reactivatable virus is present in sensory ganglion neurons after inoculation of thymidine kinase-negative mutants of herpes simplex virus type 1. J Virol, 63, 2861–2865.

    PubMed  CAS  Google Scholar 

  • Underwood, M.R., Ferris, R.G., Selleseth, D.W., Davis, M.G., Drach, J.C., Townsend, L.B., Biron, K.K. and Boyd, F.L., (2004), Mechanism of action of the ribopyranoside benzimidazole GW275175X against human cytomegalovirus. Antimicrob Agents Chemother, 48, 1647–1651.

    PubMed  CAS  Google Scholar 

  • Visse, B., Huraux, J.M. and Fillet, A.M., (1999), Point mutations in the varicella-zoster virus DNA polymerase gene confers resistance to foscarnet and slow growth phenotype. J Med Virol, 59, 84–90.

    PubMed  CAS  Google Scholar 

  • Wade, J.C., Newton, B., McLaren, C., Flournoy, N., Keeney, R.E. and Meyers, J.D., (1982), Intravenous acyclovir to treat mucocutaneous herpes simplex virus infection after marrow transplantation: a double-blind trial. Ann Intern Med, 96, 265–269.

    PubMed  CAS  Google Scholar 

  • Wang, L.H., Peck, R.W., Yin, Y., Allanson, J., Wiggs, R. and Wire, M.B., (2003), Phase I safety and pharmacokinetic trials of 1263w94, a novel oral anti-human cytomegalovirus agent, in healthy and human immunodeficiency virus-infected subjects. Antimicrob Agents Chemother, 47, 1334–1342.

    PubMed  CAS  Google Scholar 

  • Weinberg, A., Jabs, D.A., Chou, S., Martin, B.K., Lurain, N.S., Forman, M.S. and Crumpacker, C., (2003), Mutations conferring foscarnet resistance in a cohort of patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis. J Infect Dis, 187, 777–784.

    PubMed  Google Scholar 

  • Whitley, R.J. and Gnann, J.W., Jr., (1992), Acyclovir: a decade later. N Engl J Med, 327, 782–789.

    PubMed  CAS  Google Scholar 

  • Wilcox, C.L., Crnic, L.S. and Pizer, L.I., (1992), Replication, latent infection, and reactivation in neuronal culture with a herpes simplex virus thymidine kinase-negative mutant. Virology, 187, 348–352.

    PubMed  CAS  Google Scholar 

  • Wolf, D.G., Lee, D.J. and Spector, S.A., (1995a), Detection of human cytomegalovirus mutations associated with ganciclovir resistance in cerebrospinal fluid of AIDS patients with central nervous system disease. Antimicrob Agents Chemother, 39, 2552–2554.

    CAS  Google Scholar 

  • Wolf, D.G., Lurain, N.S., Zuckerman, T., Hoffman, R., Satinger, J., Honigman, A., Saleh, N., Robert, E.S., Rowe, J.M. and Kra-Oz, Z., (2003), Emergence of late cytomegalovirus central nervous system disease in hematopoietic stem cell transplant recipients. Blood, 101, 463–465.

    PubMed  CAS  Google Scholar 

  • Wolf, D.G., Smith, I.L., Lee, D.J., Freeman, W.R., Flores Aguilar, M. and Spector, S.A., (1995b), Mutations in human cytomegalovirus UL97 gene confer clinical resistance to ganciclovir and can be detected directly in patient plasma. J Clin Invest, 95, 257–263.

    CAS  Google Scholar 

  • Wolf, D.G., Yaniv, I., Honigman, A., Kassis, I., Schonfeld, T. and Ashkenazi, S., (1998), Early emergence of ganciclovir-resistant human cytomegalovirus strains in children with primary combined immunodeficiency. J Infect Dis, 178, 535–538.

    PubMed  CAS  Google Scholar 

  • Zaia, J.A., GallezHawkins, G.M., Tegtmeier, B.R., terVeer, A., Li, X.L., Niland, J.C. and Forman, S.J., (1997), Late cytomegalovirus disease in marrow transplantation is predicted by virus load in plasma. J Infect Dis, 176, 782–785.

    PubMed  CAS  Google Scholar 

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Authors
  1. G. Boivin
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  2. W. L. Drew
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Editors and Affiliations

  1. Infectious Disease, St. Michael’s Hospital, 30 Bond St., Suite 4179 Cardinal Carter Wing, Toronto, Ontario M5B 1W8, Canada

    I. W. Fong (Director) (Director)

  2. International Center for Public Health, 225 Warren Street, Newark, NJ 07103-3535, USA

    Karl Drlica

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© 2008 Springer Science+Business Media, LLC

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Boivin, G., Drew, W.L. (2008). Resistance of Herpesviruses to Antiviral Agents. In: Fong, I.W., Drlica, K. (eds) Antimicrobial Resistance and Implications for the Twenty-First Century. Emerging Infectious Diseases of the 21st Century. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-72418-8_8

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