Impact of novel mutations of herpes simplex virus 1 and 2 thymidine kinases on acyclovir phosphorylation activity.

Abstract:

:The acyclic analogue of guanosine acyclovir (ACV) constitutes the first-line drug for the treatment of herpes simplex virus (HSV) infections. ACV activation requires primophosphorylation by virus-encoded HSV thymidine kinase (TK). In 95% of cases, HSV resistance to ACV is associated with mutations located in TK. The aim of this work was to address the question of the potential involvement of novel HSV-1 and HSV-2 TK mutations in reduced susceptibility to ACV using a novel nonradioactive method, based on luminescent quantitation of ADP, for the evaluation of in vitro phosphorylation activity of TK. All recombinant TKs tested exhibited significantly lower ACV phosphorylation activities in comparison with those of reference KOS or gHSV-2 TKs (p<0.015), therefore indicating that amino acid changes Y53D, L170P, R176W, A207P (HSV-1) and S66P, A72S, I101S, M183I (HSV-2) were likely to be involved in HSV resistance to ACV.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Burrel S,Bonnafous P,Hubacek P,Agut H,Boutolleau D

doi

10.1016/j.antiviral.2012.09.016

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

386-90

issue

3

eissn

0166-3542

issn

1872-9096

pii

S0166-3542(12)00223-9

journal_volume

96

pub_type

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