Genetic analysis of a ganciclovir-resistant human cytomegalovirus mutant.

Abstract:

:We isolated a ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) from a laboratory strain, AD169, and analysed the mutant. Attempts were also made to identify directly the mutated gene. The 50% inhibitory concentration (IC50) of GCV for the mutant strain was five times higher than that of the wild-type strain. The mutant strain showed similar sensitivity to phosphonoacetic acid and cidofovir as the wild-type strain. These data suggest mutation in the UL97 gene encoding for the phosphotransferase that phosphorylates GCV. Molecular analysis of the mutant strain revealed that a single base substitution of adenine by cytosine occurred at the 1796 nucleotide position of the UL97 gene region, resulting in the substitution of lysine by threonine at codon 599 in the UL97 gene product. Marker transfer experiment confirmed that this mutation conferred HCMV resistance to GCV. The mutation at codon 599 was easily identified by means of RsaI digestion of the selected PCR product.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Faizi Khan R,Mori S,Eizuru Y,Kumura Ishii K,Minamishima Y

doi

10.1016/s0166-3542(98)00051-5

subject

Has Abstract

pub_date

1998-12-01 00:00:00

pages

95-103

issue

1-2

eissn

0166-3542

issn

1872-9096

pii

S0166-3542(98)00051-5

journal_volume

40

pub_type

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