Rapid in vitro evolution of human cytomegalovirus UL56 mutations that confer letermovir resistance

Antimicrobial Agents and Chemotherapy

Volumn 59, Issue 10, 2015, Pages 6588-6593

  Chou, Sunwen ^a  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZIMIDAVIR; FOSCARNET; LETERMOVIR; ACETIC ACID DERIVATIVE; ANTIVIRUS AGENT; QUINAZOLINE DERIVATIVE;

AMINO ACID SUBSTITUTION; ANTIVIRAL RESISTANCE; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; CODON; CONTROLLED STUDY; EC50; HUMAN; HUMAN CELL; HUMAN CYTOMEGALOVIRUS; IN VITRO SELECTION; NONHUMAN; PHENOTYPE; POINT MUTATION; PRIORITY JOURNAL; VIROGENESIS; VIRUS MUTATION; VIRUS STRAIN; CYTOMEGALOVIRUS; DRUG EFFECTS; GENETICS; MUTATION; VIRUS REPLICATION;

ACETATES; ANTIVIRAL AGENTS; CYTOMEGALOVIRUS; HUMANS; MUTATION; QUINAZOLINES; VIRUS REPLICATION;

EID: 84942888781     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.01623-15     Document Type: Article

References (33)

1. Kotton CN, Kumar D, Caliendo AM, Asberg A, Chou S, Danziger-Isakov L, Humar A. 2013. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation 96:333-360. http://dx.doi.org/10.1097/TP.0b013e31829df29d.
2. Lurain NS, Chou S. 2010. Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev 23:689-712. http://dx.doi.org/10.1128/CMR.00009-10.
3. Bogner E. 2010. Human cytomegalovirus packaging: an update on structure-function relationships. Future Virol 5:397-404. http://dx.doi.org/10.2217/fvl.10.28.
4. Underwood MR, Ferris RG, Selleseth DW, Davis MG, Drach JC, Townsend LB, Biron KK, Boyd FL. 2004. Mechanism of action of the ribopyranoside benzimidazole GW275175X against human cytomegalovirus. Antimicrob Agents Chemother 48:1647-1651. http://dx.doi.org/10.1128/AAC.48.5.1647-1651.2004.
5. Buerger I, Reefschlaeger J, Bender W, Eckenberg P, Popp A, Weber O, Graeper S, Klenk HD, Ruebsamen-Waigmann H, Hallenberger S. 2001. A novel nonnucleoside inhibitor specifically targets cytomegalovirus DNA maturation via the UL89 and UL56 gene products. J Virol 75:9077-9086. http://dx.doi.org/10.1128/JVI.75.19.9077-9086.2001.
6. Chemaly RF, Ullmann AJ, Stoelben S, Richard MP, Bornhauser M, Groth C, Einsele H, Silverman M, Mullane KM, Brown J, Nowak H, Kolling K, Stobernack HP, Lischka P, Zimmermann H, Rubsamen-Schaeff H, Champlin RE, Ehninger G. 2014. Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation. N Engl J Med 370:1781-1789. http://dx.doi.org/10.1056/NEJMoa1309533.
7. Goldner T, Hempel C, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. 2014. Geno- and phenotypic characterization of human cytomegalovirus mutants selected in vitro after letermovir (AIC246) exposure. Antimicrob Agents Chemother 58:610-613. http://dx.doi.org/10.1128/AAC.01794-13.
8. Chou S, Marousek GI. 2008. Accelerated evolution of maribavir resistancein a cytomegalovirus exonuclease domainII mutant. JVirol 82:246-253. http://dx.doi.org/10.1128/JVI.01787-07.
9. Chou S, Bowlin TL. 2011. Cytomegalovirus UL97 mutations affecting cyclopropavir and ganciclovir susceptibility. Antimicrob Agents Chemother 55:382-384. http://dx.doi.org/10.1128/AAC.01259-10.
10. Schubert A, Ehlert K, Schuler-Luettmann S, Gentner E, Mertens T, Michel D. 2013. Fast selection of maribavir resistant cytomegalovirus in a bone marrow transplant recipient. BMC Infect Dis 13:330. http://dx.doi.org/10.1186/1471-2334-13-330.
11. Strasfeld L, Lee I, Villano S, Chou S. 2010. Virologic characterization of multi-drug-resistant cytomegalovirus infection in two transplant recipients treated with maribavir. JInfect Dis 202:104-108. http://dx.doi.org/10.1086/653122.
12. Chou S, Van Wechel LC, Lichy HM, Marousek GI. 2005. Phenotyping of cytomegalovirus drug resistance mutations by using recombinant viruses incorporating a reporter gene. Antimicrob Agents Chemother 49:2710-2715. http://dx.doi.org/10.1128/AAC.49.7.2710-2715.2005.
13. Chou S. 2010. Recombinant phenotyping of cytomegalovirus UL97 kinase sequence variants for ganciclovir resistance. Antimicrob Agents Chemother 54:2371-2378. http://dx.doi.org/10.1128/AAC.00186-10.
14. Chou S. 2011. Phenotypic diversity of cytomegalovirus DNA polymerase gene variants observed after antiviral therapy. J Clin Virol 50:287-291. http://dx.doi.org/10.1016/j.jcv. 2011.01.004.
15. Warming S, Costantino N, Court DL, Jenkins NA, Copeland NG. 2005. Simple and highly efficient BAC recombineering using galK selection. Nucleic Acids Res 33:e36. http://dx.doi.org/10.1093/nar/gni035.
16. Borst EM, Kleine-Albers J, Gabaev I, Babic M, Wagner K, Binz A, Degenhardt I, Kalesse M, Jonjic S, Bauerfeind R, Messerle M. 2013. The human cytomegalovirus UL51 protein is essential for viral genome cleavage-packaging and interacts with the terminase subunits pUL56 and pUL89. J Virol 87:1720-1732. http://dx.doi.org/10.1128/JVI.01955-12.
17. Wang JB, Zhu Y, McVoy MA, Parris DS. 2012. Changes in subcellular localization reveal interactions between human cytomegalovirus terminase subunits. Virol J 9:315. http://dx.doi.org/10.1186/1743-422X-9-315.
18. Borst EM, Hahn G, Koszinowski UH, Messerle M. 1999. Cloning of the human cytomegalovirus (HCMV) genome as an infectious bacterial artificial chromosome in Escherichia coli: a new approach for construction of HCMV mutants. J Virol 73:8320-8329.
19. Murphy E, Yu D, Grimwood J, Schmutz J, Dickson M, Jarvis MA, Hahn G, Nelson JA, Myers RM, Shenk TE. 2003. Coding potential of laboratory and clinical strains of human cytomegalovirus. Proc Natl Acad Sci U S A 100:14976-14981. http://dx.doi.org/10.1073/pnas.2136652100.
20. Tischer BK, von Einem J, Kaufer B, Osterrieder N. 2006. Two-step red-mediated recombination for versatile high-efficiency markerless DNA manipulation in Escherichia coli. Biotechniques 40:191-197. http://dx.doi.org/10.2144/000112096.
21. Chou S, Marousek GI, Van Wechel LC, Li S, Weinberg A. 2007. Growth and drug resistance phenotypes resulting from cytomegalovirus DNA polymerase region III mutations observed in clinical specimens. Antimicrob Agents Chemother 51:4160-4162. http://dx.doi.org/10.1128/AAC.00736-07.
22. Chou S, Ercolani RJ, Sahoo MK, Lefterova MI, Strasfeld LM, Pinsky BA. 2014. Improved detection of emerging drug-resistant mutant cytomegalovirus subpopulations by deep sequencing. Antimicrob Agents Chemother 58:4697-4702. http://dx.doi.org/10.1128/AAC.03214-14.
23. Goldner T, Hewlett G, Ettischer N, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. 2011. The novel anticytomegalovirus compound AIC246 (letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase. J Virol 85:10884-10893. http://dx.doi.org/10.1128/JVI.05265-11.
24. Lischka P, Hewlett G, Wunberg T, Baumeister J, Paulsen D, Goldner T, Ruebsamen-Schaeff H, Zimmermann H. 2010. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246. Antimicrob Agents Chemother 54:1290-1297. http://dx.doi.org/10.1128/AAC.01596-09.
25. Baldanti F, Underwood MR, Stanat SC, Biron KK, Chou S, Sarasini A, Silini E, 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.
26. Chou S, Boivin G, Ives J, Elston R. 2014. Phenotypic evaluation of previously uncharacterized cytomegalovirus DNA polymerase sequence variants detected in a valganciclovir treatment trial. J Infect Dis 209:1219-1226. http://dx.doi.org/10.1093/infdis/jit654.
27. Chou S, Hakki M, Villano S. 2012. Effects on maribavir susceptibility of cytomegalovirus UL97 kinase ATP binding region mutations detected after drug exposure in vitro and in vivo. Antiviral Res 95:88-92. http://dx.doi.org/10.1016/j.antiviral.2012.05.013.
28. Alain S, et al. 2015. 15th Int CMV/Betaherpesvirus Workshop, Brisbane, Australia, abstr. O59.
29. Lischka P, Michel D, Zimmermann H. Characterization of cytomegalovirus breakthrough events in a letermovir (AIC246, MK 8228) phase 2 prophylaxis trial. J Infect Dis, in press.
30. Champier G, Couvreux A, Hantz S, Rametti A, Mazeron MC, Bouaziz S, Denis F, Alain S. 2008. Putative functional domains of human cytomegalovirus pUL56 involved in dimerization and benzimidazole D-ribonucleoside activity. Antivir Ther 13:643-654.
31. Goldner T, Zimmermann H, Lischka P. 2015. Phenotypic characterization of two naturally occurring human Cytomegalovirus sequence polymorphisms locatedin adistinct region of ORF UL56 knownto beinvolved in in vitro resistance to letermovir. Antiviral Res 116:48-50. http://dx.doi.org/10.1016/j.antiviral.2015.01.006.
32. Chou S, Van Wechel LC, Marousek GI. 2006. Effect of cell culture conditions on the anticytomegalovirus activity of maribavir. Antimicrob Agents Chemother 50:2557-2559. http://dx.doi.org/10.1128/AAC.00207-06.
33. Stoelben S, Arns W, Renders L, Hummel J, Muhlfeld A, Stangl M, Fischereder M, Gwinner W, Suwelack B, Witzke O, Durr M, Beelen DW, Michel D, Lischka P, Zimmermann H, Rubsamen-Schaeff H, Budde K. 2014. Preemptive treatment of cytomegalovirus infection in kidney transplant recipients with letermovir: results of a phase 2a study. Transpl Int 27:77-86. http://dx.doi.org/10.1111/tri.12225.