A fifth human cytomegalovirus glycoprotein B genotype

Shepp, David H.; Match, Mark E.; Lipson, Steven M.; Pergolizzi, Robert G.

doi:10.1016/s0923-2516(98)80086-1

Cited by 57 publications

(54 citation statements)

References 16 publications

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“…The genetic diversity of various human herpesviruses (cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1, human herpesvirus 7, and human herpesvirus 8) and methods for genotyping clinical isolates have been proposed by a number of laboratories (7,11,27,31,34,35,38,(41)(42)(43)46). Genetic diversity among VZV strains was initially defined using either restriction enzyme mapping (1, 22) or variation in the copy number at the tandem repeat regions (6,20,21,39).…”

mentioning

confidence: 99%

Complete-Genome Phylogenetic Approach to Varicella-Zoster Virus Evolution: Genetic Divergence and Evidence for Recombination

Norberg

Liljeqvist

Bergström

et al. 2006

J Virol

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Recent studies of varicella-zoster virus (VZV) DNA sequence variation, involving large numbers of globally distributed clinical isolates, suggest that this virus has diverged into at least three distinct genotypes designated European (E), Japanese (J), and mosaic (M). In the present study, we determined and analyzed the complete genomic sequences of two M VZV strains and compared them to the sequences of three E strains and two J strains retrieved from GenBank (including the Oka vaccine preparation, V-Oka). Except for a few polymorphic tandem repeat regions, the whole genome, representing approximately 125,000 nucleotides, is highly conserved, presenting a genetic similarity between the E and J genotypes of approximately 99.85%. These analyses revealed that VZV strains distinctly segregate into at least four genotypes (E, J, M1, and M2) in phylogenetic trees supported by high bootstrap values. Separate analyses of informative sites revealed that the tree topology was dependent on the region of the VZV genome used to determine the phylogeny; collectively, these results indicate the observed strain variation is likely to have resulted, at least in part, from interstrain recombination. Recombination analyses suggest that strains belonging to the M1 and M2 genotypes are mosaic recombinant strains that originated from ancestral isolates belonging to the E and J genotypes through recombination on multiple occasions. Furthermore, evidence of more recent recombination events between M1 and M2 strains is present in six segments of the VZV genome. As such, interstrain recombination in dually infected cells seems to figure prominently in the evolutionary history of VZV, a feature it has in common with other herpesviruses. In addition, we report here six novel genomic targets located in open reading frames 51 to 58 suitable for genotyping of clinical VZV isolates.In temperate climates, varicella-zoster virus (VZV) is a ubiquitous human pathogen with tropism to skin and sensory ganglia. VZV establishes latent infections, most prominently in the dorsal root and trigeminal ganglia, resulting in a permanent association with the host that may reactivate many decades after primary infection to cause herpes zoster. Primary VZV infection is nearly always symptomatic (varicella), a normally benign childhood disease; occasionally first exposure results in more serious illness or, in rare instances, death (40). Several neurological manifestations have been described in relation to VZV reactivation, such as facial palsy, encephalitis, meningitis, and cerebral vasculitis, conditions that may occur without any dermal lesions (4, 12, 16). The combined disease burden of primary and reactivated VZV infections has motivated widespread vaccination using a live, attenuated VZV strain (V-Oka). More recently, it has been demonstrated that a high-dose formulation of V-Oka can prevent or substantially ameliorate both herpes zoster and postherpetic neuralgia in persons 60 years of age and older (33).The genetic diversity of various human herpesviru...

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confidence: 99%

Complete-Genome Phylogenetic Approach to Varicella-Zoster Virus Evolution: Genetic Divergence and Evidence for Recombination

Norberg

Liljeqvist

Bergström

et al. 2006

J Virol

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“…Genetic variation among strains of human herpesviruses has been used to distinguish viral genotypes and to conduct epidemiological studies (7,14,33,40,(45)(46)(47)(48)(49)(50)(51). Variation results predominantly from single nucleotide polymorphisms (SNPs) or from alteration in the composition and number of repeat elements present either within the internal and terminal repeat regions or within tandem direct reiterations scattered throughout the genome (7,8,27,35).…”

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confidence: 99%

Phylogenetic Analysis of Varicella-Zoster Virus: Evidence of Intercontinental Spread of Genotypes and Recombination

Muir

Nichols

Breuer

2002

J Virol

136

103

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A heteroduplex mobility assay was used to identify variants of varicella-zoster virus circulating in the United Kingdom and elsewhere. Within the United Kingdom, 58 segregating sites were found out of the 23,266 examined (0.25%), and nucleotide diversity was estimated to be 0.00063. These are an order of magnitude smaller than comparable estimates from herpes simplex virus type 1. Sixteen substitutions were nonsynonymous, the majority of which were clustered within surface-expressed proteins. Extensive genetic correlation between widely spaced sites indicated that recombination has been rare. Phylogenetic analysis of varicellazoster viruses from four continents distinguished at least three major genetic clades. Most geographical regions contained only one of these three strains, apart from the United Kingdom and Brazil, where two or more strains were found. There was minimal genetic differentiation (one or fewer substitutions in 1,895 bases surveyed) between the samples collected from Africa (Guinea Bissau, Zambia) and the Indian subcontinent (Bangladesh, South India), suggesting recent rapid spread and/or low mutation rates. The geographic pattern of strain distribution would favor a major influence of the former. The genetic uniformity of most virus populations makes recombination difficult to detect. However, at least one probable recombinant between two of the major strains was found among the samples originating from Brazil, where mixtures of genotypes co-occur.

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“…Additional sequence analysis of the two CMV isolates that produced a false-negative result in the gB Q-PCR (Fig. 2) revealed that both isolates are not new but are most likely the same as the previously discovered gB genotype 5 (gB5) (16). This genotype was defined by sequence analysis of two variable regions in the CMV glycoprotein B gene and was found to be distinct from the other four gB genotypes of CMV (4).…”

Section: Discussionmentioning

confidence: 69%

“…2). A BLAST search (1) revealed that these isolates were identical (I-60) or almost identical (I-35) to the gB genotype 5 consensus sequence in the 5Ј variable region of the gB gene (16) (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

“…The glycoprotein B gene (gB, UL55) is, overall, one of the less variable regions of the CMV genome (11,17), except for two variable subregions (4,16), and has been frequently used as a target for Q-PCR assays (5,6,(8)(9)(10)19). Schaade et al (14) described a Q-PCR assay using fluorescence energy transfer technology with two fluorophore-labeled hybridization probes within the gB gene and concluded that their assay was superior in terms of sensitivity, specificity, linear range, and efficiency to the commercially available COBAS Amplicor CMV Monitor assay (Roche), which uses the CMV DNA polymerase gene (pol) as a target.…”

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confidence: 99%

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Sequence Diversity in the Glycoprotein B Gene Complicates Real-Time PCR Assays for Detection and Quantification of Cytomegalovirus

et al. 2005

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Real-time quantitative PCR systems (Q-PCRIn an effort to evaluate the impact of CMV sequence variants in our patient population by use of a similar Q-PCR assay, we surveyed 54 isolates of CMV, each from a different patient. We detected evidence for the C630T variant in 4 of 54 (7.4%) patients. Furthermore, isolates from two additional patients were completely negative in the test. Sequencing of these false-negative isolates revealed multiple mutations within the probe hybridization sites. A Q-PCR that targeted the CMV polymerase gene instead of gB detected all 54 isolates. We suggest that Q-PCR assays for viral load be rigorously tested on large panels of viral isolates to assess the impact of sequence diversity on detection as well as quantification.Real-time quantitative PCR (Q-PCR) is currently the method of choice for the rapid detection and quantification of cytomegalovirus (CMV) in clinical specimens (10, 12). The glycoprotein B gene (gB, UL55) is, overall, one of the less variable regions of the CMV genome (11, 17), except for two variable subregions (4, 16), and has been frequently used as a target for Q-PCR assays (5,6,(8)(9)(10)19). Schaade et al. (14) described a Q-PCR assay using fluorescence energy transfer technology with two fluorophore-labeled hybridization probes within the gB gene and concluded that their assay was superior in terms of sensitivity, specificity, linear range, and efficiency to the commercially available COBAS Amplicor CMV Monitor assay (Roche), which uses the CMV DNA polymerase gene (pol) as a target. Other groups, using modifications of the assay described by Schaade et al. (14), have reported similar experiences (8, 12).However, CMV variants that could not be quantified using this Q-PCR have been reported (15). In the initial report (15), 912 clinical specimens were tested, of which 197 were positive for CMV DNA, but for 12 specimens (6.1% of the positive specimens) a viral load could not be determined. The specimens that were detected but not quantified did not produce a crossing point or any evidence of amplification during the PCR. However, in the melting curve analysis following the PCR, a signal was detected with a melting temperature of 53.1°C, which is below the 59.2°C melting temperature found for wild-type CMV. Sequence analysis revealed a single base pair mutation, C630T, in the target sequence of the downstream probe (15). This sequence variant prevented the appearance of a fluorescent signal under the cycling conditions of the assay, which included an annealing temperature of 58°C (15). The melting curve employed a lower annealing temperature (45°C), which allowed hybridization of the probe with the C630T variant (15). Thus, for the C630T gB variant, the assay developed by Schaade et al. (14) was only sufficient to provide qualitative results.To evaluate the impact of sequence variants in our patient population using a similar Q-PCR assay, we studied 54 CMV isolates, each from a different patient. We found two isolates that were not detectable. Sequence analysis o...

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A fifth human cytomegalovirus glycoprotein B genotype

Cited by 57 publications

References 16 publications

Complete-Genome Phylogenetic Approach to Varicella-Zoster Virus Evolution: Genetic Divergence and Evidence for Recombination

Complete-Genome Phylogenetic Approach to Varicella-Zoster Virus Evolution: Genetic Divergence and Evidence for Recombination

Phylogenetic Analysis of Varicella-Zoster Virus: Evidence of Intercontinental Spread of Genotypes and Recombination

Sequence Diversity in the Glycoprotein B Gene Complicates Real-Time PCR Assays for Detection and Quantification of Cytomegalovirus

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