The UL97 protein kinase of human cytomegalovirus and homologues in other herpesviruses: Impact on virus and host

Biochimica et Biophysica Acta - Proteins and Proteomics

Volumn 1697, Issue 1-2, 2004, Pages 169-180

  Michel, Detlef ^a   Mertens, Thomas ^a  

^a UNIVERSITY HOSPITAL ULM   (Germany)

Author keywords

Aciclovir; ACV; CDV; Cellular elongation factor 1 delta; Cidofovir; Cytomegalovirus; EBV; EF 1 delta; Epstein Barr virus; Ganciclovir; GCV; HCMV; HHV; HSV; Human cytomegalovirus; Human herpesvirus; Inhibitor; Protein kinase; UL97 homologue; UL97 protein

Indexed keywords

12 (2 CYANOETHYL) 6,7,12,13 TETRAHYDRO 13 METHYL 5 OXOINDOLO[2,3 A]PYRROLO[3,4 C]CARBAZOLE; ABACAVIR; ACICLOVIR; AMPRENAVIR; ANTIVIRUS AGENT; BACTERIAL ENZYME; BENZIMIDAVIR; BENZIMIDAZOLE DERIVATIVE; CARBAZOLE DERIVATIVE; CIDOFOVIR; DEOXYGUANOSINE; DIDANOSINE; FOMIVIRSEN; FOSCARNET; GANCICLOVIR; GW 275175X; INDINAVIR; K 252A; K 252C; LAMIVUDINE; LEFLUNOMIDE; PHOSPHOTRANSFERASE; PROTEIN KINASE; SULFONAMIDE; TERIFLUNOMIDE; TOMEGLOVIR; UL97 PROTEIN KINASE; UNCLASSIFIED DRUG; VALGANCICLOVIR; VIRUS ENZYME; ZALCITABINE; ZIDOVUDINE;

ANTIVIRAL ACTIVITY; CLINICAL TRIAL; CONFERENCE PAPER; DRUG MECHANISM; ENZYME PHOSPHORYLATION; EPSTEIN BARR VIRUS; HERPES SIMPLEX VIRUS 1; HERPES SIMPLEX VIRUS 2; HERPES VIRUS; HOST; HUMAN; HUMAN CYTOMEGALOVIRUS; HUMAN HERPESVIRUS 6; HUMAN HERPESVIRUS 8; NONHUMAN; OPEN READING FRAME; PRIORITY JOURNAL; SEQUENCE HOMOLOGY; VARICELLA ZOSTER VIRUS; VIRUS INFECTION; VIRUS STRAIN;

ANIMALS; ANTIVIRAL AGENTS; CLINICAL TRIALS; CYTOMEGALOVIRUS; ENZYME INHIBITORS; HERPESVIRIDAE; HUMANS; PHOSPHOTRANSFERASES (ALCOHOL GROUP ACCEPTOR); VIRUS REPLICATION;

BACTERIA (MICROORGANISMS); CANINE DISTEMPER VIRUS; CUCUMBER MOSAIC VIRUS; CYTOMEGALOVIRUS; HERPESVIRIDAE; HUMAN HERPESVIRUS 1; HUMAN HERPESVIRUS 2; HUMAN HERPESVIRUS 3; HUMAN HERPESVIRUS 4; HUMAN HERPESVIRUS 5; HUMAN HERPESVIRUS 6; HUMAN HERPESVIRUS 6A; HUMAN HERPESVIRUS 8; MURINAE; SIMPLEXVIRUS;

EID: 1542358852     PISSN: 15709639     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbapap.2003.11.022     Document Type: Conference Paper

References (126)

1. Crumpacker C.S. Ganciclovir. N. Engl. J. Med. 335:1996;721-729.
2. Chrisp P., Clissold S.P. Foscarnet, a review of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with cytomegalovirus retinitis. Drugs. 41:1991;104-129.
3. Snoeck R., De Clercq E. Role of cidofovir in the treatment of DNA virus infections, other than CMV infections, in immunocompromised patients. Curr. Opin. Investig. Drugs. 3:2002;1561-1566.
4. Azad R.F., Driver V.B., Tanaka K., Crooke R.M., Anderson K.P. Antiviral activity of a phosphorothioate oligonucleotide complementary to RNA of the human cytomegalovirus major immediate-early region. Antimicrob. Agents Chemother. 37:1993;1945-1954.
5. Perry C.M., Balfour J.A. Fomivirsen. Drugs. 57:1999;375-380.
6. 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., Buhles W.C., DeArmond B. Prevalence of resistance in patients receiving ganciclovir for serious cytomegalovirus infection. J. Infect. Dis. 163:1991;716-719.
7. Jabs D.A., Enger C., Dunn J.P., Forman M. Cytomegalovirus retinitis and viral resistance: ganciclovir resistance. J. Infect. Dis. 177:1998;770-773.
8. Limaye P., Raghu G., Koelle D.M., Ferrenberg J., Huang M.-L., Boeckh M. High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving pre-emptive therapy. J. Infect. Dis. 185:2002;20-27.
9. Boivin G., Gilbert C., Gaudreau A., Greenfield I., Sudlow R., Roberts N.A. Rate of emergence of cytomegalovirus (CMV) mutations in leukocytes of patients with acquired immunodeficiency syndrome who are receiving valganiclovir as induction and maintenance therapy for CMV retinitis. J. Infect. Dis. 184:2001;1598-1602.
10. Kruger R.M., Shannon W.D., Arens M.Q., Lynch J.P., Storch G.A., Trulock E.P. The impact of ganciclovir-resistant cytomegalovirus infection after lung transplantation. Transplantation. 68:1999;1272-1279.
11. Weller T.H. The cytomegaloviruses: ubiquitous agents with protean clinical manifestations I. N. Engl. J. Med. 285:1971;203-214.
12. Boppana S.B., Pass R.F., Britt W.J., Stagno S., Alford C.A. Symptomatic congenital cytomegalovirus infection: neonatal morbidity and mortality. Pediatr. Infect. Dis. J. 11:1992;93-99.
13. Hebart H., Einsele H. Diagnosis and treatment of cytomegalovirus infection. Curr. Opin. Hematol. 5:1998;483-487.
14. Cheung T.W., Teich S.A. Cytomegalovirus infection in patients with HIV infection. Mt. Sinai J. Med. 66:1999;113-124.
15. Rowe W.P., Hartley J.W., Watermann S.et al. Cytopathogenic agent resembling salivary gland virus recovered from tissue culture of human adenoids. Proc. Soc. Exp. Biol. Med. 92:1956;418-424.
16. Cha T.A., Tom E., Kemble G.W., Duke G.M., Mocarski E.S., Spaete R.R. Human cytomegalovirus clinical isolates carry at least 19 genes not found in laboratory strains. J. Virol. 70:1996;78-83.
17. Neff B.J., Weibel R.E., Buynak E.B., McLean A.A., Hilleman M.R. Clinical and laboratory studies of live cytomegalovirus vaccine Ad-169. Proc. Soc. Exp. Biol. Med. 160:1979;32-37.
18. Plotkin S.A. Vaccination against herpes group viruses. Pediatrics. 56:1975;494-496.
19. Plotkin S.A., Smiley M.L., Friedman H.M., Starr S.E., Fleisher G.R., Wlodaver C., Dafoe D.C., Friedman A.D., Grossman R.A., Barker C.F. Towne-vaccine-induced prevention of cytomegalovirus disease after renal transplants. Lancet. 10:1984;1528-1530.
20. Plotkin S.A., Furukawa T., Zygraich N., Huygelen C. Candidate cytomegalovirus strain for human vaccination. Infect. Immun. 12:1975;521-527.
21. Curran M., Noble S. Valganciclovir. Drugs. 61:2001;1145-1150.
22. Martin J.C., Dvorak C.A., Smee D.F., Matthews T.R., Verheyden J.P. 9-[(1, 3-Dihydroxy-2-propoxy)methyl]guanine: a new potent and selective antiherpes agent. J. Med. Chem. 26:1983;759-761.
23. De Clercq E., Sakuma T., Baba M., Pauwels R., Balzarini J., Rosenberg I., Holy A. Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines. Antivir. Res. 8:1987;261-272.
24. Snoeck R., Sakuma T., De Clercq E., Rosenberg I., Holy A. (S)-1-(3-Hydroxy-2-phosphonylmethoxypropyl)cytosine, a potent and selective inhibitor of human cytomegalovirus replication. Antimicrob. Agents Chemother. 32:1988;1839-1844.
25. Biron K.K., Fyfe J.A., Stanat S.C., Leslie L.K., Sorrell J.B., Lambe C.U., Coen D.M. A human cytomegalovirus mutant resistant to the nucleoside analog 9-([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine (BW B759U) induces reduced levels of BWB759U triphosphate. Proc. Natl. Acad. Sci. U. S. A. 83:1986;8769-8773.
26. Sullivan V., Talarico C.L., Stanat S.C., Davis M., Coen D.M., Biron K.K. A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells. Nature. 358:1992;162-164.
27. Littler E., Stuart A.D., Chee M.S. Human cytomegalovirus UL97 open reading frame encodes a protein that phosphorylates the antiviral nucleoside analogue ganciclovir. Nature. 358:1992;160-162.
28. Baldanti F., Sarasini A., Silini E., Barbi M., Lazzarin A., Biron K.K., Gerna G. Four dually resistant human cytomegalovirus strains from AIDS-patients: single mutations in UL97 and UL54 open reading frames are responsible for ganciclovir- and foscarnet-specific resistance, respectively. Scand. J. Infect. Dis. Suppl. 99:1995;103-104.
29. Baldanti F., Underwood M., Talarico C.L., Simoncini L., Sarasini A., Biron K.K., Gerna G. The Cys607->Tyr change in the UL97 phosphotransferase confers ganciclovir resistance to two human cytomegalovirus strains recovered from two immunocompromised patients. Antimicrob. Agents Chemother. 42:1998;444-446.
30. Chou S., Marousek G., Guentzel S., Follansbee S.E., Poscher M.E., Lalezari J.P., Miner R.C., Drew W.L. Evolution of mutations conferring multidrug resistance during prophylaxis and therapy for cytomegalovirus disease. J. Infect. Dis. 176:1997;786-789.
31. Chou S., Meichsner C.L. A nine-codon deletion mutation in the cytomegalovirus UL97 phosphotransferase gene confers resistance to ganciclovir. Antimicrob. Agents Chemother. 44:2000;183-185.
32. Hanson M., Preheim L.C., Chou S., Talarico C.L., Biron K.K., Erice A. Novel mutation in the UL97 gene of a clinical cytomegalovirus strain conferring resistance to ganciclovir. Antimicrob. Agents Chemother. 39:1995;1204-1205.
33. Ijichi O., Michel D., Mertens Th., Miyata K., Eizuru Y. GCV resistance due to the mutation A594P in the cytomegalovirus protein UL97 is partially reconstituted by a second mutation at D605E. Antivir. Res. 53:2002;135-142.
34. Khan F.K., Mori S., Eizuru Y., Ishii K.K., Minamishima Y. Genetic analysis of a ganciclovir-resistant human cytomegalovirus mutant. Antivir. Res. 49:1998;95-103.
35. Erice A. Resistance of human cytomegalovirus to antiviral drugs. Clin. Microbiol. Rev. 12:1999;286-297.
36. Michel D., Wunderlich K., Michel M., Wasner T., Hauser I., Just M., Hampl W., Mertens Th. Fast genotypic identification and estimation of ganciclovir-resistant cytomegalovirus from clinical specimens. Scholz M. New Aspects of CMV-Related Immunopathology. Monogr. Virol. vol. 24:2003;160-170 Karger, Basel.
37. Chou S., Waldemer R.H., Senters A.E., Michels K.S., Kemble G.W., Miner R.C., Drew N.L. Cytomegalovirus UL97 phosphotransferase mutations that affect susceptibility to ganciclovir. J. Infect. Dis. 185:2002;162-169.
38. Michel D., Höhn S., Haller T., Jun D., Mertens Th. Aciclovir selects for ganciclovir-cross-resistance of human cytomegalovirus in vitro which is only in part explained by known mutations in the UL97 protein. J. Med. Virol. 65:2001;70-76.
39. 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., Crumpacker C. A standardized plaque reduction assay for determination of drug susceptibilities of cytomegalovirus clinical isolates. Antimicrob. Agents Chemother. 44:2000;688-692.
40. Chou S. Antiviral drug resistance in human cytomegalovirus. Transl. Infect. Dis. 1:1999;105-114.
41. Chou S., Erice A., Jordan M.C., Vercellotti G.M., Michels K.R., Talarico C.L., Stanat S.C., Biron K.K. Analysis of the UL97 phosphotransferase coding sequence in clinical cytomegalovirus isolates and identification of mutations conferring ganciclovir resistance. J. Infect. Dis. 171:1995;576-583.
42. Michel D., Pavic I., Zimmermann A., Haupt E., Wunderlich K., Heuschmid M., Mertens Th. The UL97 gene product of the human cytomegalovirus is an early-late protein with a nuclear localization but is not a nucleoside kinase. J. Virol. 70:1996;6340-6347.
43. Michel, Kramer S., Höhn S., Schaarschmidt P., Wunderlich K., Mertens T. Amino acids of conserved kinase motifs of the cytomegalovirus protein UL97 are essential for autophosphorylation. J. Virol. 73:1999;8898-8901.
44. He Z., He Y., Kim Y., Chu L., Ohmstede C., Biron K.K., Coen D.M. The human cytomegalovirus UL97 protein is a protein kinase that autophosphorylates on serines and threonines. J. Virol. 71:1997;405-411.
45. Marschall M., Stein-Gerlach M., Freitag M., Kupfer R., van den Bogaard M., Stamminger T. Direct targeting of human cytomegalovirus protein kinase pUL97 by kinase inhibitors is a novel principle for antiviral therapy. J. Gen. Virol. 83:2001;1013-1023.
46. Erice, Gil-Roda C., Perez J.L., Balfour H.H. Jr., Sannerud K.J., Hanson M.N., Boivin G., Chou S. Antiviral susceptibilities and analysis of UL97 and DNA polymerase sequences of clinical cytomegalovirus isolates from immunocompromised patients. J. Infect. Dis. 175:1997;1087-1092.
47. Smith L., Cherrington J.M., Jiles R.E., Fuller M.D., Freeman W.A., Spector S.A. High-level resistance of cytomegalovirus to ganciclovir is associated with alterations in both the UL97 and DNA polymerase genes. J. Infect. Dis. 176:1997;69-77.
48. Cihlar T., Fuller M.D., Cherrington J.M. 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. 72:1998;5927-5936.
49. Lurain N.S., Thompson K.D., Holmes E.W., Read G.S. Point mutations in the DNA polymerase gene of human cytomegalovirus that result in resistance to antiviral agents. J. Virol. 66:1992;7146-7152.
50. Chou S., Lurain N.S., Thompson K.D., Miner R.C., Drew W.L. Viral DNA polymerase mutations associated with drug resistance in human cytomegalovirus. J. Infect. Dis. 188:2003;32-39.
51. Chee M.S., Lawrence G.L., Barrell B.G. Alpha-, beta- and gammaherpesviruses encode a putative phosphotransferase. J. Gen. Virol. 70:1989;1151-1160.
52. Hanks S.K., Quinn A.M., Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 241:1988;42-52.
53. Michel D., Schaarschmidt P., Wunderlich K., Heuschmid M., Simoncini L., Mühlberger D., Zimmermann A., Pavic I., Mertens Th. Functional regions of the human cytomegalovirus protein pUL97 involved in nuclear localization and phosphorylation of ganciclovir and pUL97 itself. J. Gen. Virol. 79:1998;2105-2112.
54. van Zeijl M., Fairhurst J., Baum E.Z., Sun L., Jones T.R. The human cytomegalovirus UL97 protein is phosphorylated and a component of virions. Virology. 231:1997;72-80.
55. Prichard M.N., Gao N., Jairath S., Mulamba G., Krosky P., Coen D.M., Parker B.O., Pari G.S. A recombinant human cytomegalovirus with a large deletion in UL97 has a severe replication deficiency. J. Virol. 73:1999;5663-5670.
56. Wolf D.G., Courcelle C.T., Prichard M.N., Mocarski E.S. Distinct and separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA synthesis and encapsidation. Proc. Natl. Acad. Sci. U. S. A. 98:2001;1895-1900.
57. Krosky P.M., Baek M.C., Coen D.M. The human cytomegalovirus UL97 protein kinase, an antiviral drug target, is required at the stage of nuclear egress. J. Virol. 77:2003;905-914.
58. Marschall M., Freitag M., Suchy P., Romaker D., Kupfer R., Hanke M., Stamminger T. The protein kinase pUL97 of human cytomegalovirus interacts with and phosphorylates the DNA polymerase processivity factor pUL44. Virology. 311:2003;60-71.
59. Baek M.C., Krosky P.M., He Z., Coen D.M. Specific phosphorylation of exogenous protein and peptide substrates by the human cytomegalovirus UL97 protein kinase. Importance of the P+5 position. J. Biol. Chem. 277:2002;29593-29599.
60. Baek M.C., Krosky P.M., Coen D.M. Relationship between autophosphorylation and phosphorylation of exogenous substrates by the human cytomegalovirus UL97 protein kinase. J. Virol. 76:2002;11943-11952.
61. Krosky P.M., Baek M.C., Jahng W.J., Barrera I., Harvey R.J., Biron K.K., Coen D.M., Sethna P.B. The human cytomegalovirus UL44 protein is a substrate for the UL97 protein kinase. J. Virol. 77:2003;7720-7727.
62. Talarico C.L., Burnette T.C., Miller W.H., Smith S.L., Davis M.G., Stanat S.C., Ng T.I., He Z., Coen D.M., Roizman B., Biron K.K. Acyclovir is phosphorylated by the human cytomegalovirus UL97 protein. Antimicrob. Agents Chemother. 43:1999;1941-1946.
63. Zimmermann A., Michel D., Pavic I., Hampl W., Luske A., Neyts J., De Clercq E., Mertens T. Phosphorylation of aciclovir, ganciclovir, penciclovir and S2242 by the cytomegalovirus UL97 protein: a quantitative analysis using recombinant vaccinia viruses. Antivir. Res. 36:1997;35-42.
64. Shugar D. Viral and host-cell protein kinases: enticing antiviral targets and relevance of nucleoside, and viral thymidine, kinases. Pharmacol. Ther. 82:1999;315-335.
65. Baldanti F., Michel D., Simoncini L., Heuschmid M., Zimmermann A., Minisini R., Schaarschmidt P., Schmid T., Gerna G., Mertens Th. Mutations in the UL97 ORF of ganciclovir-resistant clinical cytomegalovirus isolates differentially affect GCV phosphorylation as determined in a recombinant vaccinia virus system. Antivir. Res. 54:2002;59-67.
66. Zimmermann, Wilts H., Lenhardt M., Hahn M., Mertens T. Indolocarbazoles exhibit strong antiviral activity against human cytomegalovirus and are potent inhibitors of the pUL97 protein kinase. Antivir. Res. 48:2000;49-60.
67. Romaker D., Stamminger T., Marschall M. Comparative analysis of herpesviral protein kinases (UL97 group) using trans-complemetation assays. 28th International Herpesvirus Workshop, Madison (WI, USA). 2003;6.27. abstract.
68. Wolf D.G., Honigman A., Lazarovits J., Tavor E., Panet A. Characterization of the human cytomegalovirus UL97 gene product as a virion-associated protein kinase. Arch. Virol. 143:1998;1223-1232.
69. Biron K.K., Harvey R.J., Chamberlain S.C., Good S.S., Smith A.A. III, Davis M.G., Talarico C.L., Miller W.H., Ferris R., Dornsife R.E., Stanat S.C., Drach J.C., Townsend L.B., Koszalka G.W. Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole L-riboside with a unique mode of action. Antimicrob. Agents Chemother. 46:2002;2365-2372.
70. Metzger C., Michel D., Schneider K., Lüske A., Schlicht H.-J., Mertens Th. Human cytomegalovirus UL97 kinase confers ganciclovir susceptibility to recombinant vaccinia virus. J. Virol. 68:1994;8423-8427.
71. Neyts J., Andrei G., Snoeck R., Jahne G., Winkler I., Helsberg M., Balzarini J., De Clercq E. The N-7-substituted acyclic nucleoside analog 2-amino-7-[(1, 3-dihydroxy-2-propoxy)methyl]purine is a potent and selective inhibitor of herpesvirus replication. Antimicrob. Agents Chemother. 38:1994;2710-2716.
72. Neyts J., Balzarini J., Andrei G., Chaoyong Z., Snoeck R., Zimmermann A., Mertens T., Karlsson A., De Clercq E. Intracellular metabolism of the N7-substituted acyclic nucleoside analog 2-amino-7-(1, 3-dihydroxy-2- propoxymethyl)purine, a potent inhibitor of herpesvirus replication. Mol. Pharmacol. 53:1998;157-165.
73. Swanson R., Bergquam E., Wong S.W. Characterization of rhesus cytomegalovirus genes associated with anti-viral susceptibility. Virology. 240:1998;338-348.
74. Rawlinson W.D., Zeng F., Farrell H.E., Cunningham A.L., Scalzo A.A., Booth T.W., Scott G.M. The murine cytomegalovirus (MCMV) homolog of the HCMV phosphotransferase (UL97(pk) gene. Virology. 233:1997;358-563.
75. Wagner M., Michel D., Schaarschmidt P., Vaida B., Jonjic S., Messerle M., Mertens T., Koszinowski U. Comparison between human cytomegalovirus pUL97 and murine cytomegalovirus (MCMV) pM97 expressed by MCMV and vaccinia virus: pM97 does not confer ganciclovir sensitivity. J. Virol. 74:2000;10729-10736.
76. Stals F.S., Zeytinoglu A., Havenith M., de Clercq E., Bruggeman C.A. Rat cytomegalovirus-induced pneumonitis after allogeneic bone marrow transplantation: effective treatment with (S)-1-(3-hydroxy-2-phosphonyl- methoxypropyl)cytosine. Antimicrob. Agents Chemother. 37:1993;218-223.
77. Meijer H., Dormans P.H., Geelen J.L., van Boven C.P. Rat cytomegalovirus: studies on the viral genome and the proteins of virions and nucleocapsids. J. Gen. Virol. 65:1984;681-695.
78. Fox D.S., Schleiss M.R. Sequence and transcriptional analysis of the guinea pig cytomegalovirus UL97 homolog. Virus Genes. 15:1997;255-264.
79. Reddehase M.J., Balthesen M., Rapp M., Jonjic S., Pavic I., Koszinowski U.H. The conditions of primary infection define the load of latent viral genome in organs and the risk of recurrent cytomegalovirus disease. J. Exp. Med. 179:1994;185-193.
80. Reddehase M.J., Podlech J., Grzimek N.K. Mouse models of cytomegaloviruslatency: overview. J. Clin. Virol. 25(Suppl 2):2002;S23-S36.
81. Rawlinson W.D., Farrell H.E., Barrell B.G. Analysis of the complete DNA sequence of murine cytomegalovirus. J. Virol. 70:1996;8833-8849.
82. Ng T.I., Talarico C., Burnette T.C., Biron K., Roizman B. Partial substitution of the functions of the herpes simplex virus 1 U(L)13 gene by the human cytomegalovirus U(L)97 gene. Virology. 225:1996;347-358.
83. Lucia H.L., Griffith B.P., Hsiung G.D. Effect of acyclovir and phosphonoformate on cytomegalovirus infection in guinea pigs. Intervirology. 21:1984;141-149.
84. Vink C., Beuken E., Bruggeman C.A. Complete DNA sequence of the rat cytomegalovirus genome. J Virol. 74:2000;7656-7665.
85. Fong C.K., Cohen S.D., McCormick S., Hsiung G.D. Antiviral effect of 9-(1, 3-dihydroxy-2-propoxymethyl)guanine against cytomegalovirus infection in a guinea pig model. Antivir. Res. 7:1987;11-23.
86. Bia F.J., Griffith B.P., Fong C.K., Hsiung G.D. Cytomegaloviral infections in the guinea pig: experimental models for human disease. Rev. Infect. Dis. 5:1983;177-195.
87. Hansen S.G., Strelow L.I., Franchi D.C., Anders D.G., Wong S.W. Complete sequence and genomic analysis of rhesus cytomegalovirus. J. Virol. 77:2003;6620-6636.
88. Chou S., Guentzel S., Michels K.R., Miner R.C., Drew W.L. Frequency of UL97 phosphotransferase mutations related to ganciclovir resistance in clinical cytomegalovirus isolates. J. Infect. Dis. 172:1995;239-242.
89. Wolf G., Smith L., Lee D.J., Freeman W.R., Flores-Aguilar M., Spector S.A. Mutations in human cytomegalovirus UL97 gene confer clinical resistance to ganciclovir and can be detected directly in patient plasma. J. Clin. Invest. 95:1995;257-263.
90. Kato K., Kawaguchi Y., Tanaka M., Igarashi M., Yokoyama A., Matsuda G., Kanamori M., Nakajima K., Nishimura Y., Shimojima M., Phung H.T., Takahashi E., Hirai K. Epstein-Barr virus-encoded protein kinase BGLF4 mediates hyperphosphorylation of cellular elongation factor 1delta (EF-1delta): EF-1delta is universally modified by conserved protein kinases of herpesviruses in mammalian cells. J. Gen. Virol. 82:2001;1457-1463.
91. Kawaguchi Y., Matsumura T., Roizman B., Hirai K. Cellular elongation factor 1delta is modified in cells infected with representative alpha-, beta-, or gammaherpesviruses. J. Virol. 73:1999;4456-4460.
92. Kawaguchi Y., Kato K., Tanaka M., Kanamori M., Nishiyama Y., Yamanashi Y. Conserved protein kinases encoded by herpesviruses and cellular protein kinases encoded by herpesviruses and cellular protein kinase cdc2 target the same phosphorylation site in eukaryotic elongation factor 1delta. J. Virol. 77:2003;2359-2368.
93. Gustafson E.A., Chillemi A.C., Sage D.R., Fingeroth J.D. The Epstein-Barr virus thymidine kinase does not phosphorylate ganciclovir or acyclovir and demonstrates a narrow substrate specificity compared to the herpes simplex virus type 1 thymidine kinase. Antimicrob. Agents Chemother. 42:1998;2923-2931.
94. Zacny V.L., Gershburg E., Davis M.G., Biron K.K., Pagano J.S. Inhibition of Epstein-Barr virus replication by a benzimidazole L-riboside: novel antiviral mechanism of 5, 6-dichloro-2-(isopropylamino)-1-beta-L-ribofuranosyl- 1H-benzimidazole. J. Virol. 73:1999;7271-7277.
95. Chen M.R., Chang S.J., Huang H., Chen J.Y. A protein kinase activity associated with Epstein-Barr virus BGLF4 phosphorylates the viral early antigen EA-D in vitro. J. Virol. 74:2000;3093-3104.
96. Lawrence G.L., Chee M., Craxton M.A., Gompels U.A., Honess R.W., Barrell B.G. Human herpesvirus 6 is closely related to human cytomegalovirus. J. Virol. 64:1990;287-299.
97. Gompels U.A., Nicholas J., Lawrence G., Jones M., Thomson B.J., Martin M.E., Efstathiou S., Craxton M., Macaulay H.A. The DNA sequence of human herpesvirus-6: structure, coding content, and genome evolution. Virology. 209:1995;29-51.
98. Burns W.H., Sandford G.R. Susceptibility of human herpesvirus 6 to antivirals in vitro. J. Infect. Dis. 162:1990;634-637.
99. Agut H., Collandre H., Aubin J.T., Guetard D., Favier V., Ingrand D., Montagnier L., Huraux J.M. In vitro sensitivity of human herpesvirus-6 to antiviral drugs. Res. Virol. 140:1989;219-228.
100. Ansari A., Emery V.C. The U69 gene of human herpesvirus 6 encodes a protein kinase which can confer ganciclovir sensitivity to baculoviruses. J. Virol. 73:1999;3284-3291.
101. De Bolle L., Michel D., Mertens T., Manichanh C., Agut H., De Clercq E., Naesens L. Role of the human herpesvirus 6 U69-encoded kinase in the phosphorylation of ganciclovir. Mol. Pharmacol. 62:2002;714-721.
102. Manichanh C., Olivier-Aubron C., Lagarde J.P., Aubin J.T., Bossi P., Gautheret-Dejean A., Huraux J.M., Agut H. Selection of the same mutation in the U69 protein kinase gene of human herpesvirus-6 after prolonged exposure to ganciclovir in vitro and in vivo. J. Gen. Virol. 82:2001;2767-2776.
103. Kawaguchi Y., Van Sant C., Roizman B. Eukaryotic elongation factor 1delta is hyperphosphorylated by the protein kinase encoded by the U(L)13 gene of herpes simplex virus 1. J. Virol. 72:1998;1731-1736.
104. Daikokua T., Shibatab S., Goshimaa F., Oshimaa S., Tsurumia T., Yamadaa H., Yamashita Y., Nishiyamaa Y. Purification and characterization of the protein kinase encoded by the UL13 gene of herpes simplex virus type 2. Virology. 235:1997;82-93.
105. Long M.C., Leong V., Schaffer P.A., Spencer C.A., Rice S.A. ICP22 and the UL13 protein kinase are both required for herpes simplex virus-induced modification of the large subunit of RNA polymerase II. J. Virol. 73:1999;5593-5604.
106. Koyano S., Suzutani T., Yoshida I., Azuma M. Analysis of phosphorylation pathways of antiherpesvirus nucleosides by varicella-zoster virus-specific enzymes. Antimicrob. Agents Chemother. 40:1996;920-923.
107. Ng T.I., Keenan L., Kinchington P.R., Grose C. Phosphorylation of varicella-zoster virus open reading frame (ORF) 62 regulatory product by viral ORF 47-associated protein kinase. J. Virol. 68:1994;1350-1359.
108. Ng T.I., Grose C. Serine protein kinase associated with varicella-zoster virus ORF 47. Virology. 191:1992;9-18.
109. Reddy S.M., Cox E., Iofin I., Soong W., Cohen J.I. Varicella-zoster virus (VZV) ORF32 encodes a phosphoprotein that is posttranslationally modified by the VZV ORF47 protein kinase. J. Virol. 72:1998;8083-8088.
110. Kenyon T.K., Lynch J., Hay J., Ruyechan W., Grose C. Varicella-zoster virus ORF47 protein serine kinase: characterization of a cloned, biologically active phosphotransferase and two viral substrates, ORF62 and ORF63. J. Virol. 75:2001;8854-8858.
111. Cannon J.S., Hamzeh F., Moore S., Nicholas J., Ambinder R.F. Human herpesvirus 8-encoded thymidine kinase and phosphotransferase homologues confer sensitivity to ganciclovir. J. Virol. 73:1999;4786-4793.
112. Waldman W.J., Knight D.A., Blinder L., Shen J., Lurain N.S., Miller D.M., Sedmak D.D., Williams J.W., Chong A.S. Inhibition of cytomegalovirus in vitro and in vivo by the experimental immunosuppressive agent leflunomide. Intervirology. 42:1999;412-418.
113. Waldman W.J., Knight D.A., Lurain N.S., Miller D.M., Sedmak D.D., Williams J.W., Chong A.S. Novel mechanism of inhibition of cytomegalovirus by the experimental immunosuppressive agent leflunomide. Transplantation. 68:1999;814-825.
114. Reefschlaeger J., Bender W., Hallenberger S., Weber O., Eckenberg P., Goldmann S., Haerter M., Buerger I., Trappe J., Herrington J.A., Haebich D., Ruebsamen-Waigmann H. Novel non-nucleoside inhibitors of cytomegaloviruses (BAY 38-4766): in vitro and in vivo antiviral activity and mechanism of action. J. Antimicrob. Chemother. 48:2001;757-767.
115. Townsend L.B., Devivar R.V., Turk S.R., Nassiri M.R., Drach J.C. Design, synthesis, and antiviral activity of certain 2, 5, 6-trihalo-1-(beta-D- ribofuranosyl)benzimidazoles. J. Med. Chem. 38:1995;4098-4105.
116. Buerger I., Reefschlaeger J., Bender W., Eckenberg P., Popp A., Weber O., Graeper S., Klenk H.D., Ruebsamen-Waigmann H., Hallenberger S. A novel nonnucleoside inhibitor specifically targets cytomegalovirus DNA maturation via the UL89 and UL56 gene products. J. Virol. 75:2001;9077-9086.
117. Underwood M.R., Harvey R.J., Stanat S.C., Hemphill M.L., Miller T., Drach J.C., Townsend L.B., Biron K.K. Inhibition of human cytomegalovirus DNA maturation by a benzimidazole ribonucleoside is mediated through the UL89 gene product. J. Virol. 72:1998;717-725.
118. Krosky P.M., Underwood M.R., Turk S.R., Feng K.W., Jain R.K., Ptak R.G., Westerman A.C., Biron K.K., Townsend L.B., Drach J.C. Resistance of human cytomegalovirus to benzimidazole ribonucleosides maps to two open reading frames: UL89 and UL56. J. Virol. 72:1998;4721-4728.
119. Scheffczik H., Savva C.G., Holzenburg A., Kolesnikova L., Bogner E. The terminase subunits pUL56 and pUL89 of human cytomegalovirus are DNA-metabolizing proteins with toroidal structure. Nucleic Acids Res. 30:2002;1695-1703.
120. Scholz B., Rechter S., Drach J.C., Townsend L.B., Bogner E. Identification of the ATP-binding site in the terminase subunit pUL56 of human cytomegalovirus. Nucleic Acids Res. 31:2003;1426-1433.
121. Williams S.L., Hartline C.B., Kushner N.L., Harden E.A., Bidanset D.J., Drach J.C., Townsend L.B., Underwood M.R., Biron K.K., Kern E.R. In vitro activities of benzimidazole D- and L-ribonucleosides against herpesviruses. Antimicrob. Agents Chemother. 47:2003;2186-2192.
122. McSharry J.J., McDonough A., Olson B., Talarico C., Davis M., Biron K.K. Inhibition of ganciclovir-susceptible and-resistant human cytomegalovirus clinical isolates by the benzimidazole L-riboside 1263W94. Clin. Diagn. Lab. Immunol. 8:2001;1279-1281.
123. Chou S., Senters A.E., Waldemer R.H., Davis M.G., Biron K.K. Isolation of maribavir-resistant CMV strains containing mutations in UL27. 9th International Cytomegalovirus Workshop, Maastricht, Belgium. 2003;H.03. abstract.
124. Selleseth D.W., Talarico C.L., Miller T., Lutz M.W., Biron K.K., Harvey R.J. Interactions of 1263W94 with other antiviral agents in inhibition of human cytomegalovirus replication. Antimicrob. Agents Chemother. 47:2003;1468-1471.
125. Lalezari J.P., Aberg J.A., Wang L.H., Wire M.B., Miner R., Snowden W., Talarico C.L., Shaw S., Jacobson M.A., Drew W.L. 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. 46:2002;2969-2976.
126. Slater M.J., Cockerill S., Baxter R., Bonser R.W., Gohil K., Gowrie C., Robinson J.E., Littler E., Parry N., Randall R., Snowden W. Indolocarbazoles: potent, selective inhibitors of human cytomegalovirus replication. Bioorg. Med. Chem. 7:1999;1067-1074.