A mutation in helicase motif IV of herpes simplex virus type 1 UL5 that results in reduced growth in vitro and lower virulence in a murine infection model is related to the predicted helicase structure

Journal of General Virology

Volumn 90, Issue 8, 2009, Pages 1937-1942

  Biswas, Subhajit ^a   Miguel, Ricardo Núñez ^a   Sukla, Soumi ^a   Field, Hugh J ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ACICLOVIR; DNA PRIMASE; HELICASE; ANTIVIRUS AGENT; BAY 57 1293; BAY 57-1293; HELICASE PRIMASE, HUMAN HERPESVIRUS 1; HELICASE-PRIMASE, HUMAN HERPESVIRUS 1; PYRIDINE DERIVATIVE; THIAZOLE DERIVATIVE; VIRULENCE FACTOR; VIRUS PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; ENZYME STRUCTURE; GENE MUTATION; HERPES SIMPLEX VIRUS 1; HERPES VIRUS INFECTION; MOLECULAR DOCKING; MOLECULAR INTERACTION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN MOTIF; VIRUS MUTANT; VIRUS VIRULENCE; AMINO ACID SUBSTITUTION; ANIMAL; ANTIVIRAL RESISTANCE; CHEMICAL STRUCTURE; CHEMISTRY; GENETICS; GROWTH, DEVELOPMENT AND AGING; MISSENSE MUTATION; PATHOGENICITY; PHYSIOLOGY; VIRULENCE;

HUMAN HERPESVIRUS 1; MURINAE;

AMINO ACID SUBSTITUTION; ANIMALS; ANTIVIRAL AGENTS; DNA HELICASES; DNA PRIMASE; DRUG RESISTANCE, VIRAL; HERPESVIRUS 1, HUMAN; MICE; MODELS, MOLECULAR; MUTATION, MISSENSE; PYRIDINES; THIAZOLES; VIRAL PROTEINS; VIRULENCE; VIRULENCE FACTORS;

EID: 69449084164     PISSN: 00221317     EISSN: 14652099     Source Type: Journal    
DOI: 10.1099/vir.0.011221-0     Document Type: Article

References (26)

1. Biswas, S., Jennens, L. & Field, H. J. (2007a). Single amino acid substitutions in the HSV-1 helicase protein that confer resistance to the helicase-primase inhibitor BAY 57-1293 are associated with increased or decreased virus growth characteristics in tissue culture. Arch Virol 152, 1489-1500.
2. Biswas, S., Smith, C. & Field, H. J. (2007b). Detection of HSV-1 variants highly resistant to the helicase-primase inhibitor BAY 57-1293 at high frequency in two of ten recent clinical isolates of HSV-1. J Antimicrob Chemother 60, 274-279.
3. Biswas, S. & Field, H. J. (2008). Herpes simplex virus helicase-primase inhibitors: recent findings from the study of drug-resistance mutations. Antivir Chem Chemother 19, 1-6.
4. Biswas, S., Tiley, L. S., Zimmermann, H., Birkmann, A. & Field, H. J. (2008a). Mutations close to functional motif IV in HSV-1 UL5 helicase that confer resistance to HSV helicase-primase inhibitors, variously affect virus growth rate and pathogenicity. Antiviral Res 80, 81-85.
5. Biswas, S., Kleymann, G., Swift, M., Tiley, L. S., Lyall, J., Aguirre-Hernández, J. & Field, H. J. (2008b). A single drug-resistance mutation in HSV-1 UL52 primase points to a difference between two helicase-primase inhibitors in their mode of interaction with the antiviral target. J Antimicrob Chemother 61, 1044-1047.
6. Brooks, B. R., Bruccoleri, R. E., Olafson, B. D., States, D. J., Swaminathan, S. & Karplus, M. (1983). CHARMM: a program for macromolecular energy minimization and dynamics calculations. J Comput Chem 4, 187-217. doi:10.1002/jcc.540040211.
7. de Bakker, P. I. W., Bateman, A., Burke, D. F., Miguel, R. N., Mizuguchi, K., Shi, J., Shirai, H. & Blundell, T. L. (2001). HOMSTRAD: Adding sequence information to structure-based alignments of homologous protein families. Bioinformatics 17, 748-749.
8. Dubbs, D. R. & Kit, S. (1964). Mutant strains of herpes simplex deficient in thymidine kinase-inducing activity. Virology 22, 493-502.
9. Field, H. J. & Wildy, P. (1978). The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice. J Hyg (Lond) 81, 267-277.
10. Gorbalenya, A. E. & Koonin, E. V. (1993). Helicases: amino acid sequence comparisons and structure-function relationships. Curr Opin Struct Biol 3, 419-429.
11. Graves-Woodward, K. L., Gottlieb, J., Challberg, M. D. & Weller, S. K. (1997). Biochemical analyses of mutations in the HSV-1 helicase-primase that alter ATP hydrolysis, DNA unwinding, and coupling between hydrolysis and unwinding. J Biol Chem 272, 4623-4630.
12. Jones, S. & Thornton, J. M. (1996). Principles of protein-protein interactions. Proc Natl Acad Sci U S A 93, 13-20.
13. Jones, G., Willett, P., Glen, R. C., Leach, A. R. & Taylor, R. (1997). Development and validation of a genetic algorithm for flexible docking. J Mol Biol 267, 727-748.
14. Kleymann, G., Fischer, R., Betz, U. A., Hendrix, M., Bender, W., Schneider, U., Handke, G., Eckenber, P., Hewlett, G. & other authors (2002). New helicase-primase inhibitors as drug candidates for the treatment of herpes simplex disease. Nat Med 8, 392-398.
15. Laskowski, R. A., MacArthur, M. W., Moss, D. S. & Thornton, J. M. (1993). PROCHECK: A program to check the stereochemical quality of protein structures. J Appl Crystallogr 26, 283-291.
16. Lee, B. & Richards, F. M. (1971). The interpretation of protein structures: estimation of static accessibility. J Mol Biol 55, 379-400.
17. Lee, J. Y. & Yang, W. (2006). UvrD helicase unwinds DNA one base pair at a time by a two-part power stroke. Cell 127, 1349-1360.
18. Luthy, R., Bowie, J. U. & Eisenberg, D. (1992). Assessment of protein models with 3-dimensional profiles. Nature 356, 83-85.
19. McDonald, I. K. & Thornton, J. M. (1994). Satisfying hydrogen bonding potential in proteins. J Mol Biol 238, 777-793.
20. Mizuguchi, K., Deane, C. M., Blundell, T. L., Johnson, M. S. & Overington, J. P. (1998). JOY: protein sequence-structure representation and analysis. Bioinformatics 14, 617-623.
21. Nagafuchi, S., Oda, H., Mori, R. & Taniguchi, T. (1979). Mechanism of acquired resistance to herpes simplex virus infection as studied in nude mice. J Gen Virol 44, 715-723.
22. Richmond, T. J. (1984). Solvent accessible surface area and excluded volume in proteins. Analytical equations for overlapping spheres and implications for the hydrophobic effect. J Mol Biol 178, 63-89.
23. Sali, A. & Blundell, T. L. (1993). Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234, 779-815.
24. Shi, J., Blundell, T. L. & Mizuguchi, K. (2001). FUGUE: sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties. J Mol Biol 310, 243-257.
25. Zhu, L. & Weller, S. K. (1988). UL5, a protein required for HSV DNA synthesis: genetic analysis, overexpression in Escherichia coli, and generation of polyclonal antibodies. Virology 166, 366-378.
26. Zhu, L. & Weller, S. K. (1992). The six conserved helicase motifs of the UL5 gene product, a component of the herpes simplex virus type 1 helicase primase, are essential for its function. J Virol 66, 469-479.