Effects of therapy using a helicase-primase inhibitor (HPI) in mice infected with deliberate mixtures of wild-type HSV-1 and an HPI-resistant UL5 mutant

Sukla, Soumi and Biswas, Subhajit and Birkmann, Alexander and Lischka, Peter and Ruebsamen-Schaeff, Helga and Zimmermann, Holger and Field, Hugh J. (2010) Effects of therapy using a helicase-primase inhibitor (HPI) in mice infected with deliberate mixtures of wild-type HSV-1 and an HPI-resistant UL5 mutant. Antiviral Research, 87 (1). pp. 67-73. ISSN 0166-3542

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Official URL: http://www.sciencedirect.com/science/article/pii/S...

Abstract

Point mutations in the HSV-1 UL5 (helicase) gene confer resistance to helicase-primase inhibitors (HPIs), e.g. BAY 57-1293. Such mutations normally occur at a frequency of < or =10(-6)PFU. However, individual HSV-1 laboratory strains and some clinical isolates contained resistance mutations (e.g. UL5: Lys356Asn) at 10(-4)PFU. To address the possibility that pre-existing mutants at high frequency might have an impact on therapy using HPIs, deliberate mixtures were prepared to contain the SC16 UL5: Lys356Asn mutant in SC16 wild-type in the proportion of 1/500 or 1/50PFU. Mice were infected in the neck-skin with 5x10(4)PFU/mouse of wt alone, mutant alone, or the respective mixture. The mutant could not be detected in infectious virus yields from mice inoculated with the 1/500 mixture. However, resistant mutant was recovered from some treated mice inoculated with the 1/50 mixture. All mice inoculated with mixtures remained responsive to BAY 57-1293-therapy with no increase in clinical signs compared to treatment of wt-infected mice.

Item Type:Article
Keywords:HSV, antivirals, antiviral resistance, murine infection model, BAY 57-1293
Subjects:C Biological Sciences > C540 Virology
C Biological Sciences > C520 Medical and Veterinary Microbiology
A Medicine and Dentistry > A300 Clinical Medicine
Divisions:College of Science > School of Life Sciences
ID Code:6957
Deposited By:INVALID USER
Deposited On:25 Nov 2012 21:35
Last Modified:21 Jul 2014 07:53

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