STRANSKA R, VAN LOON AM, POLMAN M, LOEF C, NIENHUIS E, SCHUURMAN R; Interscience Conference on Antimicrobial Agents and Chemotherapy (42nd : 2002 : San Diego, Calif.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2002 Sep 27-30; 42: abstract no. V-920.
University Medical Center Utrecht, Utrecht, Netherlands
BACKGROUND: Herpes simplex virus (HSV) reactivation can cause serious illness in immunocompromised patients. Systemic prophylaxis with acyclovir (ACV) has become a common practice, however, exposure to ACV may create a selective environment for emergence of resistant viruses. We examined the relationship between susceptibility to ACV and mutations in thymidine kinase (TK) gene in HSV-1 isolates from bone marrow transplant (BMT) recipients suffering from clinically significant HSV infections despite ACV prophylaxis. METHODS: ACV susceptibilities of 19 isolates from 6 BMT recipients were determined by a colorimetric drug susceptibility assay ELVIRA HSV (Diagnostic Hybrids, Inc.) and confirmed by plaque reduction assay. The sequence of the TK gene was determined. Sequencing results were compared with the known sequence of reference strain KOS (HSV-1) and sensitive isolates from patients when available. RESULTS: All 6 patients had infections caused by ACV-resistant virus. Sequencing of the TK gene revealed ten nonsilent mutations associated with gene polymorphism, which were reported earlier. Eight new amino acid substitutions at positions G129D, R163H, P209S, R216H, Y239F, A278S, A365V, R370P, that could be associated with the ACV resistance, were detected. Three previously described mutations; substitution G200D and 2 frameshift mutations at positions 146 and 185, associated with ACV resistance, were found. CONCLUSIONS: The results of susceptibility testing correlated with the clinical course of HSV infection. The study underlines the importance of the susceptibility monitoring in BMT recipients and provides additional data on the TK mutations associated with ACV resistance of HSV.
Publication Types:
Keywords:
- Acyclovir
- Base Sequence
- Bone Marrow Transplantation
- Herpes Simplex
- Herpesvirus 1, Human
- Humans
- Immunocompromised Host
- Mutation
- Plaque Assay
- Simplexvirus
- Thymidine Kinase
- genetics
- immunology
- surgery
- transplantation
Other ID:
UI: 102267126
From Meeting Abstracts