Resistance of human cytomegalovirus to cyclopropavir maps to a base pair deletion in the open reading frame of UL97

Antimicrobial Agents and Chemotherapy

Volumn 57, Issue 9, 2013, Pages 4343-4348

  Gentry, Brian G ^a   Vollmer, Laura E ^a   Hall, Ellie D ^a   Borysko, Katherine Z ^c   Zemlicka, Jiri ^d   Kamil, Jeremy P ^b   Drach, John C ^c  

^a DRAKE UNIVERSITY   (United States)

^b LOUISIANA STATE UNIVERSITY   (United States)

^c UNIVERSITY OF MICHIGAN   (United States)

^d WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOPROPAVIR; GANCICLOVIR; NUCLEOSIDE ANALOG; PROTEIN KINASE; PROTEIN KINASE PUL97; UNCLASSIFIED DRUG; VIRUS DNA;

ARTICLE; BASE PAIRING; CONTROLLED STUDY; DNA SYNTHESIS; ENZYME PHOSPHORYLATION; HUMAN; HUMAN CELL; HUMAN CYTOMEGALOVIRUS; HYPOTHESIS; NONHUMAN; OPEN READING FRAME; PRIORITY JOURNAL; VIRUS CONCENTRATION; VIRUS GENOME; VIRUS ISOLATION; WILD TYPE;

ANTIVIRAL AGENTS; BASE SEQUENCE; CELLS, CULTURED; CYCLOPROPANES; CYTOMEGALOVIRUS; DRUG RESISTANCE, VIRAL; FIBROBLASTS; FRAMESHIFT MUTATION; GANCICLOVIR; GUANINE; HUMANS; MOLECULAR SEQUENCE DATA; OPEN READING FRAMES; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; VIRAL PROTEINS;

EID: 84882322059     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00214-13     Document Type: Article

References (49)

1. Ho M. 2008. The history of cytomegalovirus and its diseases. Med. Microbiol. Immunol. 197:65-73.
2. Manicklal S, Emery VC, Lazzarotto T, Boppana SB, Gupta RK. 2013. The "silent" global burden of congenital cytomegalovirus. Clin. Microbiol. Rev. 26:86-102.
3. Andrei G, De Clercq E, Snoeck R. 2009. Drug targets in cytomegalovirus infection. Infect. Disord. Drug Targets 9:201-222.
4. Biron KK. 2006. Antiviral drugs for cytomegalovirus diseases. Antiviral Res. 71:154-163.
5. Cocohoba JM, McNickoll IR. 2002. Valganciclovir: an advance in cytomegalovirus therapeutics. Ann. Pharmacother. 36:1075-1079.
6. Faulds D, Heel RC. 1990. Ganciclovir: a review of its antiviral activity, pharmacokinetic properties, and therapeutic efficacy in cytomegalovirus infections. Drugs 39:597-638.
7. Noble S, Faulds D. 1998. Ganciclovir: an update of its use in the prevention of cytomegalovirus infection and disease in transplant recipients. Drugs 56:115-146.
8. Whitley RJ, Jacobson MA, Friedberg DN, Holland GN, Jabs DA, Dieterich DT, Hardy WD, Polis MA, Deutsch TA, Feinberg J, Spector SA, Walmsley S, Drew WL, Powderly WG, Griffiths PD, Benson CA, Kessler HA. 1998. Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA. Arch. Intern. Med. 158:957-969.
9. Littler E, Stuart AD, Chee MS. 1992. Human cytomegalovirus UL97 open reading frame encodes a protein that phosphorylates the antiviral nucleoside analogue ganciclovir. Nature 358:160-162.
10. He Z, He YS, Kim Y, Chu L, Ohmstede C, Biron KK, Coen DM. 1997. The human cytomegalovirus UL97 protein is a protein kinase that autophosphorylates on serines and threonines. J. Virol. 71:405-411.
11. Biron KK, Stanat SC, Sorrell JB, Fyfe JA, Keller PM, Lambe CU, Nelson DJ. 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. U. S. A. 82: 2473-2477.
12. Boehme RE. 1984. Phosphorylation of the antiviral precursor 9-(1,3-dihydroxy-2-propoxymethyl)guanine monophosphate by guanylate kinase isozymes. J. Biol. Chem. 259:12346-12349.
13. Freitas VR, Smee DF, Chernow M, Boehme R, Matthews TR. 1985. Activity of 9-(1,3-dihydroxy-2-propoxymethyl)guanine compared with that of acyclovir against human, monkey, and rodent cytomegaloviruses. Antimicrob. Agents Chemother. 28:240-245.
14. Matthews T, Boehme R. 1988. Antiviral activity and mechanism of action of ganciclovir. Rev. Infect. Dis. 10:S490-S494.
15. Hamzeh FM, Lietman PS, Gibson W, Hayward GS. 1990. Identification of the lytic origin of DNA replication in human cytomegalovirus by a novel approach utilizing ganciclovir-induced chain termination. J. Virol. 64:6184-6195.
16. Hamzeh FM, Lietman PS. 1991. Intranuclear accumulation of subgenomic noninfectious human cytomegalovirus DNA in infected cells in the presence of ganciclovir. Antimicrob. Agents Chemother. 35:1818-1823.
17. Baldanti F, Lurain N, Gerna G. 2004. Clinical and biologic aspects of human cytomegalovirus resistance to antiviral drugs. Hum. Immunol. 65:403-409.
18. Gilbert C, Bestman-Smith J, Boivin G. 2002. Resistance of herpesviruses to antiviral drugs: clinical impacts and molecular mechanisms. Drug Resist. Updat. 5:88-114.
19. Gilbert C, Boivin G. 2005. Human cytomegalovirus resistance to antiviral drugs. Antimicrob. Agents Chemother. 49:873-883.
20. Bowlin TL, Brooks JL, Zemlicka J. 2009. Preclinical pharmacokinetic, toxicokinetic and toxicology results for cyclopropavir, a promising new agent for the treatment of beta-and gamma-herpesviruses. Antiviral Res. 82:A46-A47.
21. Kern ER, Bidanset DJ, Harline CB, Yan Z, Zemlicka J, Quenelle DC. 2004. Oral activity of a methylenecyclopropane analog, cyclopropavir, in animal models for cytomegalovirus infections. Antimicrob. Agents Chemother. 48:4745-4753.
22. Zhou S, Breitenbach JM, Borysko KZ, Drach JC, Kern ER, Gullen E, Cheng YC, Zemlicka J. 2004. Synthesis and antiviral activity of (Z)-and (E)-2,2-[bis(hydroxymethyl)cyclopropylidene]methylpurines and-pyrimidines: second-generation methylenecyclopropane analogues of nucleosides. J. Med. Chem. 47:566-575.
23. Kern ER, Kushner NL, Hartline CB, Williams-Aziz SL, Harden EA, Zhou S, Zemlicka J, Prichard MN. 2005. In vitro activity and mechanism of action of methylenecyclopropane analogs of nucleosides against herpesvirus replication. Antimicrob. Agents Chemother. 49:1039-1045.
24. Gentry BG, Kamil JP, Coen DM, Zemlicka J, Drach JC. 2010. Stereoselective phosphorylation of cyclopropavir by pUL97 and competitive inhibition by maribavir. Antimicrob. Agents Chemother. 54:3093-3098.
25. Gentry BG, Gentry SN, Jackson TL, Zemlicka J, Drach JC. 2011. Phosphorylation of antiviral and endogenous nucleotides to di-and triphosphates by guanosine monophosphate kinase. Biochem. Pharmacol. 81:43-49.
26. Shipman C, Jr. 1969. Evaluation of 4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid (HEPES) as a tissue culture buffer. Proc. Soc. Exp. Biol. Med. 130:305-310.
27. Hobom U, Brune W, Messerle M, Hahn G, Koszinowski UH. 2000. Fast screening procedures for random transposon libraries of cloned herpesvirus genomes: mutational analysis of human cytomegalovirus envelope glycoprotein genes. J. Virol. 74:7720-7729.
28. Klein RJ. 1975. Isolation of herpes simplex virus clones and drug resistant mutants in microcultures. Arch. Virol. 49:73-80.
29. Kamil JP, Coen DM. 2007. Human cytomegalovirus protein kinase UL97 forms a complex with the tegument phosphoprotein pp65. J. Virol. 81: 10659-10668.
30. Tischer BK, von Einem J, Kaufer B, Osterrieder N. 2006. Two-step red-mediated recombination for versatile high-efficiency markerlessDNA manipulation in Escherichia coli. Biotechniques 40:191-197.
31. Tischer BK, Smith GA, Osterrieder N. 2010. En passant mutagenesis: a two step markerless red recombination system. Methods Mol. Biol. 634: 421-430.
32. Wang D, Li G, Schauflinger M, Nguyen CC, Hall ED, Yurochko AD, von Einem J, Kamil JP. 2013. The ULb= region of the human cytomegalovirus genome confers an increased requirement for the viral protein kinase UL97. J. Virol. 87:6359-6376.
33. Kalejta RF, Bechtel JT, Shenk T. 2003. Human cytomegalovirus pp71 stimulates cell cycle progression by inducing the proteasome-dependent degradation of the retinoblastoma family of tumor suppressors. Mol. Cell. Biol. 23:1885-1895.
34. Jarosinski KW, Hunt HD, Osterrieder N. 2010. Down-regulation of MHC class I by the Marek's disease virus (MDV) UL49.5 gene product mildly affects virulence in a haplotype-specific fashion. Virology. 405: 457-463.
35. Michel D, Pavic I, Zimmermann A, Haupt E, Wunderlich K, Heuschmid M, Mertens T. 1996. The UL97 gene product of human cytomegalovirus is an early-late protein with a nuclear localization but is not a nucleoside kinase. J. Virol. 70:6340-6346.
36. Sullivan V, Talarico CL, Stanat SC, Davis M, Coen DM, Biron KK. 1992. A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells. Nature 358:162-164.
37. Prichard MN, Gao N, Jairath S, Mulamba G, Krosky P, Coen DM, Parker BO, Pari GS. 1999. A recombinant human cytomegalovirus with a large deletion in UL97 has a severe replication deficiency. J. Virol. 73: 5663-5670.
38. James SH, Hartline CB, Harden EA, Driebe EM, Schupp JM, Engelthaler DM, Keim PS, Bowlin TL, Kern ER, Prichard MN. 2011. Cyclopropavir inhibits the normal function of the human cytomegalovirus UL97 kinase. Antimicrob. Agents Chemother. 55:4682-4691.
39. Komazin G, Ptak RG, Emmer BT, Townsend LB, Drach JC. 2003. Resistance of human cytomegalovirus to the benzimidazole L-ribonucleoside maribavir maps to UL27. J. Virol. 77:11499-11506.
40. Prichard MN. 2009. Function of human cytomegalovirus UL97 kinase in viral infection and its inhibition by maribavir. Rev. Med. Virol. 19:215-229.
41. Chou S, Bowlin TL. 2011. Cytomegalovirus UL97 mutations affecting cyclopropavir and ganciclovir susceptibility. Antimicrob. Agents Chemother. 55:382-384.
42. Marschall M, Stein-Gerlach M, Freitag M, Kupfer R, van Den Bogaard M, Stamminger T. 2001. Inhibitors of human cytomegalovirus replication drastically reduce the activity of the viral protein kinase pUL97. J. Gen. Virol. 82(Part 6):1439-1450.
43. Michel D, Schaarschmidt P, Wunderlich K, Heuschmid M, Simoncini L, Muhlberger D, Zimmermann A, Pavic I, Mertens T. 1998. Functional regions of the human cytomegalovirus protein pUL97 involved in nuclear localization and phosphorylation of ganciclovir and pUL97 itself. J. Gen. Virol. 79(Part 9):2105-2112.
44. Chou S, Marousek G, Bowlin TL. 2012. Cyclopropavir susceptibility of cytomegalovirus DNA polymerase mutants selected after antiviral drug exposure. Antimicrob. Agents Chemother. 56:197-201.
45. Erice A. 1999. Resistance of human cytomegalovirus to antiviral drugs. Clin. Microbiol. Rev. 12:286-297.
46. Chou S, Wechel LC, Marousek GI. 2007. Cytomegalovirus UL97 kinase mutations that confer maribavir resistance. J. Infect. Dis. 196:91-94.
47. Evers DL, Komazin G, Ptak RG, Shin D, Emmer BT, Townsend LB, Drach JC. 2004. Inhibition of human cytomegalovirus replication by benzimidazole nucleosides involves three distinct mechanisms. Antimicrob. Agents Chemother. 48:3918-3927.
48. Chou S. 2008. Cytomegalovirus UL97 mutations in the era of ganciclovir and maribavir. Rev. Med. Virol. 18:233-246.
49. Baldanti F, Sarasini A, Drach JC, Zemlicka J, Gerna G. 2002. Z-isomers of 2-hydroxymethylcyclopropylidenemethyl adenine (synadenol) and guanine (synguanol) are active against ganciclovir-and foscarnetresistant human cytomegalovirus UL97 mutants. Antiviral Res. 56:273-278.