Characterization of the DNA polymerase gene of human herpesvirus 6

Teo, Ian; Griffin, Beverly E.; Jones, Michael D.

doi:10.1128/jvi.65.9.4670-4680.1991

Cited by 63 publications

(27 citation statements)

References 59 publications

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“…The mutation in D1/3/4 and D6/3/1 is found between regions IV and A. The homology among herpesvirus DNA polymerases sequences remains high between these two regions, although the sequence conservation is not found outside this virus group (12,34).…”

Section: Resultsmentioning

confidence: 94%

“…4). The leucine residue at position 501 which is changed to isoleucine in both D6/3/1 and D1/3/4 is conserved in all human herpesvirus DNA polymerases (34). The phenylalanine residue at position 412 which is changed to valine in D10/3/2 is con-POLYMERASE MUTANTS OF HUMAN CYTOMEGALOVIRUS Standards consisting of GCV and GCV monophosphate were run on the same column to determine relative retention times.…”

Section: Resultsmentioning

confidence: 99%

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Point mutations in the DNA polymerase gene of human cytomegalovirus that result in resistance to antiviral agents

Lurain

Thompson

Holmes

et al. 1992

J Virol

132

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Three independently isolated mutants of human cytomegalovirus strain AD169 were found to be resistant to ganciclovir at a 50%o effective dose of 200 FM. Phosphorylation of ganciclovir was reduced 10-fold in mutant-infected cells compared with AD169-infected cells. All three mutants were also determined to be resistant to the nucleotide analogs (S)-1-[(3-hydroxy-2-phosphonylmethoxy)propyljadenine (HPMPA) and (S)-1-[(3-hydroxy-2-phosphonylmethoxy)propylJcytosine (HPMPC) and hypersensitive to thymine-l-D-arabinofuranoside (AraT). Single base changes resulting in amino acid substitutions were demonstrated in the nucleotide sequence of the DNA polymerase gene of each mutant. The polymerase mutation contained in one of the mutants was transferred to the wild-type AD169 background. Ganciclovir phosphorylation in cells infected with the recombinant virus produced by this transfer was found to be equivalent to that of AD169-infected cells. The ganciclovir resistance of the recombinant was reduced fourfold compared with that of the parental mutant; however, the recombinant remained resistant to HPMPA and HPMPC and hypersensitive to AraT. The ganciclovir resistance of the mutants therefore appears to result from mutations in two genes: (i) a kinase which phosphorylates ganciclovir and (ii) the viral DNA polymerase.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Point mutations in the DNA polymerase gene of human cytomegalovirus that result in resistance to antiviral agents

Lurain

Thompson

Holmes

et al. 1992

J Virol

132

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“…Domain II is one of the most conserved regions of the herpes virus DNA polymerases [Larder et al, 1987;Teo et al, 1991] and has been suggested as a strong candidate for the pyrophosphate binding site [Larder et al, 1987]. On the basis of genetic analysis of HSV and HCMV resistant strains [Larder et al, 1987;Gibbs et al, 1988;Baldanti et al, 1996], it was observed that amino acid substitutions which confer PFA-and/or PAA-resistance are clustered in this region.…”

Section: Discussionmentioning

confidence: 99%

“…Two PFA-resistance [Gibbs et al, 1988;Wong et al, 1988;Hwang et al, 1992]. Below is shown the amino acid sequence of domains II and III from a number of herpesvirus DNA polymerase including : HSV-1, HSV-2, EBV, CMV, HHV-6 [Teo et al, 1991], and HHV-7 [Nicholas, 1996]. Amino acids identical to the VZV sequence are shaded and on consensus (CON), point indicates amino acid relatively conserved in all herpes viruses.…”

Section: Discussionmentioning

confidence: 99%

Point mutations in the varicella-zoster virus DNA polymerase gene confers resistance to foscarnet and slow growth phenotype

Visse¹,

Huraux²,

Fillet³

1999

J. Med. Virol.

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Seven independent laboratory mutants were derived from seven distinct wild-type varicella-zoster virus (VZV) isolates after exposure to increasing concentrations of foscarnet (PFA) and were found to be resistant to this drug. Single base changes resulting in amino acid substitutions were observed in the nucleotide sequence of the DNA polymerase gene of each PFA-resistant mutant. The mutations were found to occur within the domain II (Arg-665 --> Gly for strains vrMOR and vrVER; Val-666 --> Leu for vrLEB; Gln-692 --> Arg for vrOLI) and domain III (Arg-806 --> Ser for vrABD; Leu-809 --> Ser for vrALI and vrCHA) of DNA polymerase gene. In addition, the PFA-resistant mutants exhibited a phenotype characterized by slow growth, the strains showing a marked delay in immediate-early antigen plaque formation compared with the wild-type VZV from which they were derived. These results may have implications for successful isolation and characterization of PFA-resistant strains from clinical samples containing mixed viral populations.

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“…This assay consists of multiplex PCR amplification to detect simultaneously HSV-1, HSV-2, VZV, EBV, CMV, HHV-6A and HHV-6B genomes that are expected to be present in a single specimen, and DNA microarray hybridization to identify accurately the specific PCR products. DNA polymerase gene of human herpes viruses has been reported as a highly conserved and homogeneous gene [Teo et al, 1991] and it was selected as the target gene in this study. Primers and oligonucleotide probes were designed on the conserved regions of this gene.…”

Section: Discussionmentioning

confidence: 99%

DNA microarray technology for simultaneous detection and species identification of seven human herpes viruses

Zheng

et al. 2008

Journal of Medical Virology

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The aim of the study was to develop a multiplex PCR-based DNA microarray technology for simultaneous detection and species identification of seven human herpes viruses, namely herpes simplex virus type 1, type 2 (HSV-1, HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus 6 (HHV-6A, HHV-6B), and to apply this technology to accurate diagnosis of herpesvirus-associated diseases. Primers and oligonucleotide probes were designed and synthesized based on the highly conserved regions of the DNA polymerase gene in human herpes viruses. DNA microarrays were made by printing the oligonucleotide probes onto special glass slides. After amplification and labeling with CY5, the PCR products were hybridized with the DNA microarrays and species identified. Sixty-one cerebrospinal fluid (CSF) and 132 blood specimens were analyzed by this technique, and the results were compared with those of TaqMan PCR. Several specimens were sequenced further after cloning. The PCR products of the seven human herpes viruses ranged from 224 to 252 bp, and could be species identified with DNA microarrays. The detection limits were 10(1) copies/microl for each virus. And the test showed no cross-reaction to DNA extracted from S. aureus, E. coli, hepatitis B virus, Cryptococcus neoformans, Candida albicans and human genome. Among 132 blood and 61 CSF specimens, 55 were tested positive for human herpes virus DNA. Compared with the results of TaqMan PCR, the sensitivity and specificity of the DNA microarray technology was 96.2% and 99.3%, respectively. This multiplex PCR-based DNA microarray technology, which is rapid, specific and sensitive, serves as an effective technique for simultaneous detection and species identification of seven human herpes viruses.

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Characterization of the DNA polymerase gene of human herpesvirus 6

Cited by 63 publications

References 59 publications

Point mutations in the DNA polymerase gene of human cytomegalovirus that result in resistance to antiviral agents

Point mutations in the DNA polymerase gene of human cytomegalovirus that result in resistance to antiviral agents

Point mutations in the varicella-zoster virus DNA polymerase gene confers resistance to foscarnet and slow growth phenotype

DNA microarray technology for simultaneous detection and species identification of seven human herpes viruses

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