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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

Biswas, Subhajit and Jennens, Lyn and Field, Hugh J. (2007) 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. Archives of Virology, 152 (8). pp. 1489-1500. ISSN 0304-8608

Full content URL: http://link.springer.com/article/10.1007%2Fs00705-...

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Item Type:Article
Item Status:Live Archive

Abstract

Two mutants (BAYr1 and BAYr2) that are 100-fold and >3000-fold resistant, respectively, to the helicase-primase inhibitor (HPI) BAY 57-1293 were derived from a plaque-pure parental strain, HSV-1 SC16 cl-2. BAYr1 has two substitutions in the HSV-1 helicase (UL5) protein (A4 to V; K356 to Q) and BAYr2 has one (G352 to R). It was shown reproducibly that BAYr1 grows to higher titres in tissue culture while BAYr2 grows more slowly than wild-type. Marker transfer experiments confirmed that K356Q and G352R are the drug-resistance mutations and that they are directly associated with differences in virus growth in tissue culture. When BAYr1 was tested in a murine infection model, this virus was shown to be fully pathogenic. We present evidence that single mutations close to a predicted functional domain of an essential HSV-1 replication enzyme (helicase) are associated with drug resistance and virus growth characteristics.

Keywords:Virus mutation, DNA virus, Antivirals
Subjects:C Biological Sciences > C540 Virology
C Biological Sciences > C521 Medical Microbiology
Divisions:College of Science > School of Life Sciences
ID Code:9378
Deposited On:10 May 2013 09:01

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