Abstract:
:Sixteen herpes simplex virus type 1 (HSV-1) and four type 2 (HSV-2) isolates resistant to acyclovir (ACV) were characterized retrospectively for drug resistance. Phenotypic testing was performed by means of tetrazolium reduction assay and genotypic analysis was carried out by sequencing of thymidine kinase (TK) and DNA-polymerase (pol) genes. All strains were characterized as cross-resistant to penciclovir, brivudin and susceptible to cidofovir. In addition, three strains were resistant to foscarnet. Genotypic analysis revealed two to seven non-synonymous mutations in the TK gene of HSV-1 and one to seven non-synonymous mutations in the DNA pol gene of HSV-1 and 2 associated with the gene polymorphism. Seventeen strains contained at least one non-synonymous resistant-related mutation in the TK gene and three strains, which were additionally foscarnet-resistant, revealed one resistance-associated mutation in the DNA pol gene. In most strains, resistant-related mutations in TK gene represented frameshift mutations and single non-synonymous nucleotide substitutions of conserved gene regions. However, numerous amino acid changes could not be interpreted clearly as accounting for resistance. In conclusion, further studies, e.g. site-directed mutagenesis experiments are required to characterize mutations of the TK and DNA pol genes in ACV-resistant viral strains as part of viral gene polymorphism or as cause of drug resistance.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Sauerbrei A,Deinhardt S,Zell R,Wutzler Pdoi
10.1016/j.antiviral.2010.03.002subject
Has Abstractpub_date
2010-06-01 00:00:00pages
246-52issue
3eissn
0166-3542issn
1872-9096pii
S0166-3542(10)00386-4journal_volume
86pub_type
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 杂志文章,随机对照试验
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更新日期:2007-09-01 00:00:00
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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更新日期:2014-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2018-02-01 00:00:00