Mechanism of antiviral drug resistance of vaccinia virus: Identification of residues in the viral DNA polymerase conferring differential resistance to antipoxvirus drugs

Journal of Virology

Volumn 82, Issue 24, 2008, Pages 12520-12534

  Gammon, Don B ^a   Snoeck, Robert ^b   Fiten, Pierre ^b   Krečmerová, Marcela ^c   Holý, Antonín ^c   De Clercq, Erik ^b   Opdenakker, Ghislain ^b   Evans, David H ^a   Andrei, Graciela ^b  

^a UNIVERSITY OF ALBERTA   (Canada)

^b REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^c INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY   (Czech Republic)

Author keywords

[No Author keywords available]

Indexed keywords

1 [3 HYDROXY 2 (PHOSPHONO METHOXYPROPYL) 2,6 DIAMINOPURINE; 1 [3 HYDROXY 2 (PHOSPHONOMETHOXY)PROPYL] 5 AZACYTOSINE; 6 [3 HYDROXY 2 (PHOSPHONOMETHOXY)PROPOXY] 2,4 DIAMINOPYRIMIDINE; 9 [3 HYDROXY 2 (PHOSPHONOMETHOXY)PROPYL] 3 DEAZAADENINE; ACYCLIC NUCLEOSIDE PHOSPHONATE; ADENINE DERIVATIVE; ANTIVIRUS AGENT; CIDOFOVIR; DEOXYADENOSINE; DEOXYCYTIDINE; DNA POLYMERASE; NUCLEOTIDE DERIVATIVE; PHOSPHONIC ACID DERIVATIVE; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG; VIRUS DNA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIVIRAL RESISTANCE; ARTICLE; CONTROLLED STUDY; DNA MODIFICATION; DNA SEQUENCE; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG EFFECT; DRUG SENSITIVITY; DRUG STRUCTURE; MOUSE; NONHUMAN; PHENOTYPE; POXVIRUS; PRIORITY JOURNAL; VACCINIA VIRUS; VIROGENESIS; VIRULENCE; VIRUS INFECTION; VIRUS ISOLATION; VIRUS MUTATION; VIRUS REPLICATION; VIRUS VIRULENCE;

AMINO ACID SEQUENCE; ANIMALS; ANTIVIRAL AGENTS; BIOLOGICAL MARKERS; CONSERVED SEQUENCE; CYCLIZATION; DNA-DIRECTED DNA POLYMERASE; MICE; MOLECULAR SEQUENCE DATA; MUTATION; NUCLEOSIDES; PHOSPHONIC ACIDS; POXVIRIDAE; SEQUENCE ALIGNMENT; VACCINIA VIRUS;

MUS; POXVIRIDAE; VACCINIA VIRUS;

EID: 57349132991     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.01528-08     Document Type: Article

References (58)

1. Andrei, G., P. Fiten, M. Froeyen, E. De Clercq, G. Opdenakker, and R. Snoeck. 2007. DNA polymerase mutations in drug-resistant herpes simplex virus mutants determine in vivo neurovirulence and drug-enzyme interactions. Antivir. Ther. 12:719-732.
2. Andrei, G., D. B. Gammon, P. Fiten, E. De Clercq, G. Opdenakker, R. Snoeck, and D. H. Evans. 2006. Cidofovir resistance in vaccinia virus is linked to diminished virulence in mice. J. Virol. 80:9391-9401.
3. Baldanti, F., N. Lurain, and G. Gerna. 2004. Clinical and biologic aspects of human cytomegalovirus resistance to antiviral drugs. Hum. Immunol. 65:403-409.
4. Balzarini, J., C. Pannecouque, L. Naesens, G. Andrei, R. Snoeck, E. De Clercq, D. Hockova, and A. Holy. 2004. 6-[2-Phosphonomethoxy)alkoxy]-2,4- diaminopyrimidines: a new class of acyclic pyrimidine nucleoside phosphonates with antiviral activity. Nucleosides Nucleotides Nucleic Acids 23:1321-1327.
5. Becker, M. N., M. Obraztsova, E. R. Kern, D. C. Quenelle, K. A. Keith, M. N. Prichard, M. Luo, and R. W. Moyer. 2008. Isolation and characterization of cidofovir resistant vaccinia viruses. Virol. J. 5:58.
6. Bray, M. 2003. Pathogenesis and potential antiviral therapy of complications of smallpox vaccination. Antivir. Res. 58:101-114.
7. Brodie, R., A. J. Smith, R. L. Roper, V. Tcherepanov, and C. Upton. 2004. Base-By-Base: single nucleotide-level analysis of whole viral genome alignments. BMC Bioinformatics 5:96.
8. Brown, J., C. K. Janniger, R. A. Schwartz, and N. B. Silverberg. 2006. Childhood molluscum contagiosum. Int. J. Dermatol. 45:93-99.
9. Chou, S. W. 2001. Cytomegalovirus drug resistance and clinical implications. Transpl. Infect. Dis. 3(Suppl. 2):20-24.
10. Ciesla, S. L., J. Trahan, W. B. Wan, J. R. Beadle, K. A. Aldern, G. R. Painter, and K. Y. Hostetler. 2003. Esterification of cidofovir with alkoxyalkanols increases oral bioavailability and diminishes drug accumulation in kidney. Antivir. Res. 59:163-171.
11. Dal Pozzo, F., G. Andrei, A. Holy, J. van den Oord, A. Scagliarini, E. De Clercq, and R. Snoeck. 2005. Activities of acyclic nucleoside phosphonates against Orf virus in human and ovine cell monolayers and organotypic ovine raft cultures. Antimicrob. Agents Chemother. 49:4843-4852.
12. Darling, R. G., C. L. Catlett, K. D. Huebner, and D. G. Jarrett. 2002. Threats in bioterrorism. I. CDC category A agents. Emerg. Med. Clin. N. Am. 20:273-309.
13. De Clercq, E. 1996. Therapeutic potential of cidofovir (HPMPC, Vistide) for the treatment of DNA virus (i.e. herpes-, papova-, pox- and adenovirus) infections. Verh. K. Acad. Geneeskd. Belg. 58:19-47.
14. De Clercq, E. 2001. Vaccinia virus inhibitors as a paradigm for the chemotherapy of poxvirus infections. Clin. Microbiol. Rev. 14:382-397.
15. De Clercq, E. 2002. Cidofovir in the treatment of poxvirus infections. Antivir. Res. 55:1-13.
16. De Clercq, E. 2007. Acyclic nucleoside phosphonates: past, present and future. Bridging chemistry to HIV, HBV, HCV, HPV, adeno-, herpes-, and poxvirus infections: the phosphonate bridge. Biochem. Pharmacol. 73:911-922.
17. De Clercq, E. 2007. The acyclic nucleoside phosphonates from inception to clinical use: historical perspective. Antivir. Res. 75:1-13.
18. De Clercq, E., G. Andrei, J. Balzarini, P. Leyssen, L. Naesens, J. Neyts, C. Pannecouque, R. Snoeck, C. Ying, D. Hockova, and A. Holy. 2005. Antiviral potential of a new generation of acyclic nucleoside phosphonates, the 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines. Nucleosides Nucleotides Nucleic Acids 24:331-341.
19. De Clercq, E., and A. Holy. 2005. Acyclic nucleoside phosphonates: a key class of antiviral drugs. Nat. Rev. Drug Discov. 4:928-940.
20. De Clercq, E., and J. Neyts. 2004. Therapeutic potential of nucleoside/ nucleotide analogues against poxvirus infections. Rev. Med. Virol. 14:289-300.
21. Di Giulio, D. B., and P. B. Eckburg. 2004. Human monkeypox: an emerging zoonosis. Lancet Infect. Dis. 4:15-25.
22. Duraffour, S., R. Snoeck, R. de Vos, J. J. van Den Oord, J. M. Crance, D. Garin, D. E. Hruby, R. Jordan, E. De Clercq, and G. Andrei. 2007. Activity of the anti-orthopoxvirus compound ST-246 against vaccinia, cowpox and camelpox viruses in cell monolayers and organotypic raft cultures. Antivir. Ther. 12:1205-1216.
23. Duraffour, S., R. Snoeck, M. Krecmerova, J. van den Oord, R. de Vos, A. Holy, J. M. Crance, D. Garin, E. De Clercq, and G. Andrei. 2007. Activities of several classes of acyclic nucleoside phosphonates against camelpox virus replication in different cell culture models. Antimicrob. Agents Chemother. 51:4410-4419.
24. Fenner, F. 1982. A successful eradication campaign. Global eradication of smallpox. Rev. Infect. Dis. 4:916-930.
25. Fenner, F. 1993. Smallpox: emergence, global spread, and eradication. Hist. Philos. Life Sci. 15:397-420.
26. Franklin, M. C., J. Wang, and T. A. Steitz. 2001. Structure of the replicating complex of a pol alpha family DNA polymerase. Cell 105:657-667.
27. Gilbert, C., J. Bestman-Smith, and G. Boivin. 2002. Resistance of herpesviruses to antiviral drugs: clinical impacts and molecular mechanisms. Drug Resist. Updat. 5:88-114.
28. Gilbert, C., and G. Boivin. 2005. Human cytomegalovirus resistance to antiviral drugs. Antimicrob. Agents Chemother. 49:873-883.
29. Gilbert, P. A., and G. McFadden. 2006. Poxvirus cancer therapy. Recent patents. Anti-Infect. Drug Discov. 1:309-321.
30. Hockova, D., A. Holy, M. Masojidkova, G. Andrei, R. Snoeck, E. De Clercq, and J. Balzarini. 2003. 5-substituted-2,4-diamino-6-[2- (phosphonomethoxy)-ethoxy]pyrimidines - acyclic nucleoside phosphonate analogues with antiviral activity. J. Med. Chem. 46:5064-5073.
31. Jahrling, P. B., E. A. Fritz, and L. E. Hensley. 2005. Countermeasures to the bioterrorist threat of smallpox. Curr. Mol. Med. 5:817-826.
32. Kile, J. C., A. T. Fleischauer, B. Beard, M. J. Kuehnert, R. S. Kanwal, P. Pontones, H. J. Messersmith, R. Teclaw, K. L. Karem, Z. H. Braden, I. Damon, A. S. Khan, and M. Fischer. 2005. Transmission of monkeypox among persons exposed to infected prairie dogs in Indiana in 2003. Arch. Pediatr. Adolesc. Med. 159:1022-1025.
33. Kornbluth, R. S., D. F. Smee, R. W. Sidwell, V. Snarsky, D. H. Evans, and K. Y. Hostetler. 2006. Mutations in the E9L polymerase gene of cidofovir-resistant vaccinia virus strain WR are associated with the drug resistance phenotype. Antimicrob. Agents Chemother. 50:4038-4043.
34. Krecmerova, M., A. Holy, A. Piskala, M. Masojidkova, G. Andrei, L. Naesens, J. Neyts, J. Balzarini, E. De Clercq, and R. Snoeck. 2007. Antiviral activity of triazine analogues of 1-(S)-[3-hydroxy-2- (phosphonomethoxy)propyl] cytosine (cidofovir) and related compounds. J. Med. Chem. 50:1069-1077.
35. Krecmerova, M., A. Holy, R. Pohl, M. Masojidkova, G. Andrei, L. Naesens, J. Neyts, J. Balzarini, E. De Clercq, and R. Snoeck. 2007. Ester prodrugs of cyclic 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine: synthesis and antiviral activity. J. Med. Chem. 50:5765-5772.
36. Lebeau, I., G. Andrei, M. Krecmerova, E. De Clercq, A. Holy, and R. Snoeck. 2007. Inhibitory activities of three classes of acyclic nucleoside phosphonates against murine polyomavirus and primate simian virus 40 strains. Antimicrob. Agents Chemother. 51:2268-2273.
37. Liu, S., J. D. Knafels, J. S. Chang, G. A. Waszak, E. T. Baldwin, M. R. Deibel, Jr., D. R. Thomsen, F. L. Homa, P. A. Wells, M. C. Tory, R. A. Poorman, H. Gao, X. Qiu, and A. P. Seddon. 2006. Crystal structure of the herpes simplex virus 1 DNA polymerase. J. Biol. Chem. 281:18193-18200.
38. Magee, W. C., K. A. Aldern, K. Y. Hostetler, and D. H. Evans. 2008. Cidofovir and (S)-9-[3-hydroxy-(2-phosphonomethoxy)propyl]adenine are highly effective inhibitors of vaccinia virus DNA polymerase when incorporated into the template strand. Antimicrob. Agents Chemother. 52:586-597.
39. Magee, W. C., K. Y. Hostetler, and D. H. Evans. 2005. Mechanism of inhibition of vaccinia virus DNA polymerase by cidofovir diphosphate. Antimicrob. Agents Chemother. 49:3153-3162.
40. Parker, S., E. Touchette, C. Oberle, M. Almond, A. Robertson, L. C. Trost, B. Lampert, G. Painter, and R. M. Buller. 2008. Efficacy of therapeutic intervention with an oral ether-lipid analogue of cidofovir (CMX001) in a lethal mousepox model. Antivir. Res. 77:39-49.
41. Prichard, M. N., and E. R. Kern. 2005. Orthopoxvirus targets for the development of antiviral therapies. Curr. Drug Targets Infect. Disord. 5:17-28.
42. Quenelle, D. C., D. J. Collins, W. B. Wan, J. R. Beadle, K. Y. Hostetler, and E. R. Kern. 2004. Oral treatment of cowpox and vaccinia virus infections in mice with ether lipid esters of cidofovir. Antimicrob. Agents Chemother. 48:404-412.
43. Ruiz, J. C., J. R. Beadle, K. A. Aldern, K. A. Keith, C. B. Hartline, E. R. Kern, and K. Y. Hostetler. 2007. Synthesis and antiviral evaluation of alkoxyalkyl-phosphate conjugates of cidofovir and adefovir. Antivir. Res. 75:87-90.
44. Shen, Y., and J. Nemunaitis. 2005. Fighting cancer with vaccinia virus: teaching new tricks to an old dog. Mol. Ther. 11:180-195.
45. Sliva, K., and B. Schnierle. 2007. From actually toxic to highly specific - novel drugs against poxviruses. Virol. J. 4:8.
46. Snoeck, R., G. Andrei, and E. De Clercq. 1996. Patterns of resistance and sensitivity to antiviral compounds of drug-resistant strains of human cytomegalovirus selected in vitro. Eur. J. Clin. Microbiol. Infect. Dis. 15:574-579.
47. Snoeck, R., G. Andrei, and E. De Clercq. 2007. Therapy of poxvirus infections, p. 375-395. In A. A. Mercer, A. Schmidt, and O. Weber (ed.), Poxviruses. Birkhäuser Verslag, Basel, Switzerland.
48. Snoeck, R., A. Holy, C. Dewolf-Peeters, J. van den Oord, E. De Clercq, and G. Andrei. 2002. Antivaccinia activities of acyclic nucleoside phosphonate derivatives in epithelial cells and organotypic cultures. Antimicrob. Agents Chemother. 46:3356-3361.
49. Spicer, E. K., J. Rush, C. Fung, L. J. Reha-Krantz, J. D. Karam, and W. H. Konigsberg. 1988. Primary structure of T4 DNA polymerase. Evolutionary relatedness to eucaryotic and other procaryotic DNA polymerases. J. Biol. Chem. 263:7478-7486.
50. Stittelaar, K. J., J. Neyts, L. Naesens, G. van Amerongen, R. F. van Lavieren, A. Holy, E. De Clercq, H. G. Niesters, E. Fries, C. Maas, P. G. Mulder, B. A. van der Zeijst, and A. D. Osterhaus. 2006. Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection. Nature 439:745-748.
51. Taddie, J. A., and P. Traktman. 1991. Genetic characterization of the vaccinia virus DNA polymerase: identification of point mutations conferring altered drug sensitivities and reduced fidelity. J. Virol. 65:869-879.
52. Taddie, J. A., and P. Traktman. 1993. Genetic characterization of the vaccinia virus DNA polymerase: cytosine arabinoside resistance requires a variable lesion conferring phosphonoacetate resistance in conjunction with an invariant mutation localized to the 3′-5′ exonuclease domain. J. Virol. 67:4323-4336.
53. Tyring, S. K. 2003. Molluscum contagiosum: the importance of early diagnosis and treatment. Am. J. Obstet. Gynecol. 189:S12-S16.
54. Vora, S., I. Damon, V. Fulginiti, S. G. Weber, M. Kahana, S. L. Stein, S. I. Gerber, S. Garcia-Houchins, E. Lederman, D. Hruby, L. Collins, D. Scott, K. Thompson, J. V. Barson, R. Regnery, C. Hughes, R. S. Daum, Y. Li, H. Zhao, S. Smith, Z. Braden, K. Karem, V. Olson, W. Davidson, G. Trindade, T. Bolken, R. Jordan, D. Tien, and J. Marcinak. 2008. Severe eczema vaccinatum in a household contact of a smallpox vaccinee. Clin. Infect. Dis. 46:1555-1561.
55. Vorou, R. M., V. G. Papavassiliou, and I. N. Pierroutsakos. 2008. Cowpox virus infection: an emerging health threat. Curr. Opin. Infect. Dis. 21:153-156.
56. Wang, G. P., and F. D. Bushman. 2006. A statistical method for comparing viral growth curves. J. Virol. Methods 135:118-123.
57. Whitley, R. J. 2003. Smallpox: a potential agent of bioterrorism. Antivir. Res. 57:7-12.
58. Yang, G., D. C. Pevear, M. H. Davies, M. S. Collett, T. Bailey, S. Rippen, L. Barone, C. Burns, G. Rhodes, S. Tohan, J. W. Huggins, R. O. Baker, R. L. Buller, E. Touchette, K. Waller, J. Schriewer, J. Neyts, E. DeClercq, K. Jones, D. Hruby, and R. Jordan. 2005. An orally bioavailable antipoxvirus compound (ST-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus challenge. J. Virol. 79:13139-13149.