کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2511056 | 1118003 | 2008 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: 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 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](/preview/png/2511056.png)
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.
Journal: Antiviral Research - Volume 80, Issue 1, October 2008, Pages 81–85