Variation within the glycoprotein B gene of human cytomegalovirus is due to homologous recombination.

Haberland, Michael; Meyer-K√∂nig, U; Hufert, Frank T.

doi:10.1099/0022-1317-80-6-1495

Cited by 60 publications

(51 citation statements)

References 27 publications

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“…Evidence for strain recombination has also been observed among clinical isolates of human herpesvirus 8 (34), cytomegalovirus (18), and Epstein-Barr virus isolates (28,45). As such, homologous recombination appears to be a general feature of human herpesvirus evolution and an important mechanism for maintaining genetic diversity among human herpesvirus strains.…”

Section: Discussionmentioning

confidence: 97%

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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Section: Discussionmentioning

confidence: 97%

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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“…Clinical isolates of human cytomegalovirus (HCMV) show significant sequence diversity by RFLP analysis and sequencing of selected ORFs (10,13,15,43). Furthermore, it is difficult to assign HCMV isolates into strain groups, due to a relatively high frequency of recombination, indicated by variation of gB via intragenic recombination and relative rarity of genetic linkages between nine separate variable loci (20,48). Similarly, a study of sequence variation between clinical isolates for genes within the Us region of HSV-1 (gG, gI, and gE) concluded that homologous recombination (intra-and intergenic) was a common event (40).…”

Section: Discussionmentioning

confidence: 99%

Analysis of Equid Herpesvirus 1 Strain Variation Reveals a Point Mutation of the DNA Polymerase Strongly Associated with Neuropathogenic versus Nonneuropathogenic Disease Outbreaks

Nugent

Birch-Machin

Smith

et al. 2006

J Virol

264

344

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Equid herpesvirus 1 (EHV-1) can cause a wide spectrum of diseases ranging from inapparent respiratory infection to the induction of abortion and, in extreme cases, neurological disease resulting in paralysis and ultimately death. It has been suggested that distinct strains of EHV-1 that differ in pathogenic capacity circulate in the field. In order to investigate this hypothesis, it was necessary to identify genetic markers that allow subgroups of related strains to be identified. We have determined all of the genetic differences between a neuropathogenic strain (Ab4) and a nonneuropathogenic strain (V592) of EHV-1 and developed PCR/ sequencing procedures enabling differentiation of EHV-1 strains circulating in the field. The results indicate the occurrence of several major genetic subgroups of EHV-1 among isolates recovered from outbreaks over the course of 30 years, consistent with the proposal that distinct strains of EHV-1 circulate in the field. Moreover, there is evidence that certain strain groups are geographically restricted, being recovered predominantly from outbreaks occurring in either North America or Europe. Significantly, variation of a single amino acid of the DNA polymerase is strongly associated with neurological versus nonneurological disease outbreaks. Strikingly, this variant amino acid occurs at a highly conserved position for herpesvirus DNA polymerases, suggesting an important functional role.Equid herpesvirus 1 (EHV-1), a member of the subfamily Alphaherpesvirinae, is a highly prevalent equine pathogen that can cause a range of clinical signs, from respiratory distress to the induction of abortion, neonatal foal death, and occasionally neurological damage resulting in paralysis (9,14,19,33,37,61). The severity of disease resulting from EHV-1 infection is likely to be influenced by a number of factors, including the age and physical condition of the host; whether the infection is primary, a reinfection, or a reactivation of latent virus; the immune status of the host; and the pathogenic potential of the strain involved. In order to assess the relative importance of EHV-1 strain variation regarding disease outcome, it is necessary to develop methods enabling precise discrimination between genetic subgroups of interrelated strains. Previous studies have utilized DNA restriction fragment length polymorphism (RFLP) to separate field isolates of EHV-1 into subgroups according to characteristic restriction enzyme site changes and the presence of variable numbers of copies of short sequence repeats. These studies demonstrated a relatively low frequency of genetic polymorphism for EHV-1 and suggested that distinct strains of EHV-1 do exist in the field (3,4,8,25,32,41,54,57). However, the relative lack of variation of EHV-1 sequences between strains has resulted in too few RFLP variants to be identified for detailed epidemiological studies. Furthermore, although such analyses may be used for tracing the genetic relatedness of strains, they allow identification only of those genetic changes resul...

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“…Other factors that could affect melting temperature, such as the primer and probe purification, DNA extraction, and PCR conditions, were similar in Schaade's and our study except for a difference in the annealing temperature (58 and 55°C, respectively). Genetic heterogeneities of CMV glycoprotein B gene from patients with different clinical backgrounds were previously described (12,34). While all of the patients in our study had solid organ transplantation, Schaade et al did not specify the clinical histories of their patients.…”

Section: Discussionmentioning

confidence: 99%

Comparison of LightCycler-Based PCR, COBAS Amplicor CMV Monitor, and pp65 Antigenemia Assays for Quantitative Measurement of Cytomegalovirus Viral Load in Peripheral Blood Specimens from Patients after Solid Organ Transplantation

et al. 2003

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In order to evaluate the LightCycler-based PCR (LC-PCR) as a diagnostic assay technique, a classical pp65antigenemia assay and the commercially available COBAS Amplicor CMV Monitor (CACM) assay were compared to the LC-PCR assay for the detection and quantitation of cytomegalovirus (CMV) load in 404 parallel specimens of peripheral blood from 66 patients after solid organ transplantation. A good correlation existed among these three assays (r Х 0.6, P < 0.0001). The LC-PCR assay was the most sensitive (54% of specimens positive) compared to the CACM (48.6%) and the pp65 antigenemia (26%) assays. The LC-PCR assay detected all samples found positive by using both the CMV pp65 antigenemia assay and the CACM assay. The LC-PCR also had the widest dynamic range (from 250 to 10 7 DNA copies/ml of plasma). No cross-reactions were found among CMV and Epstein-Barr virus, varicella-zoster virus, or herpes simplex virus in the LC-PCR by using amplification with specifically designed primer pairs. Precision, expressed as the coefficient of variation, was <3% with standard DNA from cell cultures and between 6.55 and 14.1% with clinical specimens in repeat LC-PCR runs. One run of the LC-PCR took half of the time required for the semiautomated CACM procedure. Because of its sensitivity, specificity, cost-effectiveness, and simplicity, the LC-PCR assay could replace the pp65 antigenemia and the CACM assays as the preferred technique for the surveillance, diagnosis, and monitoring of response of CMV diseases in high-risk populations.

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Variation within the glycoprotein B gene of human cytomegalovirus is due to homologous recombination.

Cited by 60 publications

References 27 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

Analysis of Equid Herpesvirus 1 Strain Variation Reveals a Point Mutation of the DNA Polymerase Strongly Associated with Neuropathogenic versus Nonneuropathogenic Disease Outbreaks

Comparison of LightCycler-Based PCR, COBAS Amplicor CMV Monitor, and pp65 Antigenemia Assays for Quantitative Measurement of Cytomegalovirus Viral Load in Peripheral Blood Specimens from Patients after Solid Organ Transplantation

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