Biswas, Subhajit and Tiley, Laurence S. and Zimmermann, Holger and Birkmann, Alexander and Field, Hugh J. (2008) 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 Research, 80 (1). pp. 81-85. ISSN 0166-3542
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Official URL: http://www.sciencedirect.com/science/article/pii/S...
Herpes simplex virus (HSV) helicase-primase (HP) is the target for a novel class of antiviral compounds, the helicase-primase inhibitors (HPIs), e.g. BAY 57-1293. Although mutations in herpesviruses conferring resistance to nucleoside analogues are commonly associated with attenuation in vivo, to date, this is not necessarily true for HPIs. HPI-resistant HSV mutants selected in tissue culture are reported to be equally pathogenic compared to parental virus in animal models. Here we demonstrate that a slow-growing HSV-1 mutant, with the BAY 57-1293-resistance mutation Gly352Arg in UL5 helicase, is clearly less virulent than its wild-type parent in a murine zosteriform infection model. This contrasts with published results obtained for a mutant containing a different HPI-resistance substitution (Gly352Val) at the same location, since this mutant was reported to be fully pathogenic. We believe our report to be the first to describe an HPI-resistant HSV-1 mutant, that is markedly less virulent in vivo and slowly growing in tissue culture compared to the parental strain. Another BAY 57-1293-resistant UL5 mutant (Lys356Gln), which showed faster growth characteristics in cell culture, however, was at least equally virulent compared to the parent strain.
|Keywords:||virus, growth curve, helicase, primase, BAY 57-1293, antiviral, herpes simplex|
|Subjects:||C Biological Sciences > C540 Virology|
C Biological Sciences > C520 Medical and Veterinary Microbiology
C Biological Sciences > C440 Molecular Genetics
A Medicine and Dentistry > A300 Clinical Medicine
|Divisions:||College of Science > School of Life Sciences|
|Deposited By:||Subhajit Biswas|
|Deposited On:||26 Nov 2012 09:38|
|Last Modified:||15 Nov 2013 16:58|
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