| 1. |
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| 2. |
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| 3. |
- Bowen, C. D., et al.
(författare)
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Comparison of Herpes Simplex Virus 1 Strains Circulating in Finland Demonstrates the Uncoupling of Whole-Genome Relatedness and Phenotypic Outcomes of Viral Infection
- 2019
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Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 93:8
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Tidskriftsartikel (refereegranskat)abstract
- A majority of adults in Finland are seropositive carriers of herpes simplex viruses (HSV). Infection occurs at epithelial or mucosal surfaces, after which virions enter innervating nerve endings, eventually establishing lifelong infection in neurons of the sensory or autonomic nervous system. Recent data have highlighted the genetic diversity of HSV-1 strains and demonstrated apparent geographic patterns in strain similarity. Though multiple HSV-1 genomes have been sequenced from Europe to date, there is a lack of sequenced genomes from the Nordic countries. Finland's history includes at least two major waves of human migration, suggesting the potential for diverse viruses to persist in the population. Here, we used HSV-1 clinical isolates from Finland to test the relationship between viral phylogeny, genetic variation, and phenotypic characteristics. We found that Finnish HSV-1 isolates separated into two distinct phylogenetic groups, potentially reflecting historical waves of human (and viral) migration into Finland. Each HSV-1 isolate harbored a distinct set of phenotypes in cell culture, including differences in the amount of virus production, extracellular virus release, and cell-type-specific fitness. Importantly, the phylogenetic clusters were not predictive of any detectable pattern in phenotypic differences, demonstrating that whole-genome relatedness is not a proxy for overall viral phenotype. Instead, we highlight specific gene-level differences that may contribute to observed phenotypic differences, and we note that strains from different phylogenetic groups can contain the same genetic variations. IMPORTANCE Herpes simplex viruses (HSV) infect a majority of adults. Recent data have highlighted the genetic diversity of HSV-1 strains and demonstrated apparent genomic relatedness between strains from the same geographic regions. We used HSV-1 clinical isolates from Finland to test the relationship between viral genomic and geographic relationships, differences in specific genes, and characteristics of viral infection. We found that viral isolates from Finland separated into two distinct groups of genomic and geographic relatedness, potentially reflecting historical patterns of human and viral migration into Finland. These Finnish HSV-1 isolates had distinct infection characteristics in multiple cell types tested, which were specific to each isolate and did not group according to genomic and geographic relatedness. This demonstrates that HSV-1 strain differences in specific characteristics of infection are set by a combination of host cell type and specific viral gene-level differences.
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| 4. |
- Breuer, Judith, et al.
(författare)
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A proposal for a common nomenclature for viral clades that form the genus varicella-zoster virus.
- 2010
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 91:4, s. 821-828
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Tidskriftsartikel (refereegranskat)abstract
- Varicella zoster virus (VZV), the cause of chickenpox and zoster, was the first human herpesvirus to be sequenced fully and the first for which vaccines have been licensed and widely used. Three groups have published genotyping schemes based on single nucleotide polymorphisms (SNP) and between them identified five distinct phylogenetic clades, with an additional two putative clades . Sequencing of over 23 whole VZV genomes from around the world further refined the phylogenic distinctions between SNP genotypes. Widespread surveillance in countries in which varicella vaccine is now in use and the difficulties posed by three unique genotyping approaches, prompted an international meeting at which a common nomenclature based on phylogenetic clades , was agreed upon. In this paper we review the original genotyping schemes and discuss the basis for a novel common nomenclature for VZV viruses. We propose a minimum set of SNPs which we recommend should be used to genotype viruses. Finally, we suggest criteria by which new clades can be recognized.
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| 5. |
- Currier, Russell W, et al.
(författare)
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The evolution of infectious agents in relation to sex in animals and humans: brief discussions of some individual organisms.
- 2011
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 1749-6632 .- 0077-8923. ; 1230, s. 74-107, s. 74-107
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Forskningsöversikt (refereegranskat)abstract
- The following series of concise summaries addresses the evolution of infectious agents in relation to sex in animals and humans from the perspective of three specific questions: (1) what have we learned about the likely origin and phylogeny, up to the establishment of the infectious agent in the genital econiche, including the relative frequency of its sexual transmission; (2) what further research is needed to provide additional knowledge on some of these evolutionary aspects; and (3) what evolutionary considerations might aid in providing novel approaches to the more practical clinical and public health issues facing us currently and in the future?
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| 6. |
- Depledge, D. P., et al.
(författare)
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High Viral Diversity and Mixed Infections in Cerebral Spinal Fluid from Cases of Varicella Zoster Virus Encephalitis
- 2018
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 218:10, s. 1592-1601
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Tidskriftsartikel (refereegranskat)abstract
- Background. Varicella zoster virus (VZV) may cause encephalitis, both with and without rash. Here we investigate whether viruses recovered from the central nervous system (CNS; encephalitis or meningitis) differ genetically from those recovered from non-CNS samples. Methods. Enrichment-based deep sequencing of 45 VZV genomes from cerebral spinal fluid (CSF), plasma, bronchoalveolar lavage (BAL), and vesicles was carried out with samples collected from 34 patients with and without VZV infection of the CNS. Results. Viral sequences from multiple sites in the same patient were identical at the consensus level. Virus from vesicle fluid and CSF in cases of meningitis showed low-level diversity. By contrast, plasma, BAL, and encephalitis had higher numbers of variant alleles. Two CSF-encephalitis samples had high genetic diversity, with variant frequency patterns typical of mixed infections with different clades. Conclusions. Low viral genetic diversity in vesicle fluid is compatible with previous observations that VZV skin lesions arise from single or low numbers of virions. A similar result was observed in VZV from cases of VZV meningitis, a generally self-limiting infection. CSF from cases of encephalitis had higher diversity with evidence for mixed clade infections in 2 cases. We hypothesize that reactivation from multiple neurons may contribute to the pathogenesis of VZV encephalitis.
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| 7. |
- Gatherer, D., et al.
(författare)
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ICTV Virus Taxonomy Profile: Herpesviridae 2021
- 2021
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 102:10
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Forskningsöversikt (refereegranskat)abstract
- Members of the family Herpesviridae have enveloped, spherical virions with characteristic complex structures consisting of symmetrical and non-symmetrical components. The linear, double-stranded DNA genomes of 125-241 kbp contain 70-170 genes, of which 43 have been inherited from an ancestral herpesvirus. In general, herpesviruses have coevolved with and are highly adapted to their hosts, which comprise many mammalian, avian and reptilian species. Following primary infection, they are able to establish lifelong latent infection, during which there is limited viral gene expression. Severe disease is usually observed only in the foetus, the very young, the immunocompromised or following infection of an alternative host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Herpesviridae, which is available at ictv.global/report/herpesviridae.
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| 8. |
- Gustafsson, Joel, et al.
(författare)
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Fast parallel construction of variable-length Markov chains
- 2021
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Ingår i: Bmc Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alignment-free methods are a popular approach for comparing biological sequences, including complete genomes. The methods range from probability distributions of sequence composition to first and higher-order Markov chains, where a k-th order Markov chain over DNA has 4k formal parameters. To circumvent this exponential growth in parameters, variable-length Markov chains (VLMCs) have gained popularity for applications in molecular biology and other areas. VLMCs adapt the depth depending on sequence context and thus curtail excesses in the number of parameters. The scarcity of available fast, or even parallel software tools, prompted the development of a parallel implementation using lazy suffix trees and a hash-based alternative. Results: An extensive evaluation was performed on genomes ranging from 12Mbp to 22Gbp. Relevant learning parameters were chosen guided by the Bayesian Information Criterion (BIC) to avoid over-fitting. Our implementation greatly improves upon the state-of-the-art even in serial execution. It exhibits very good parallel scaling with speed-ups for long sequences close to the optimum indicated by Amdahl's law of 3 for 4 threads and about 6 for 16 threads, respectively. Conclusions: Our parallel implementation released as open-source under the GPLv3 license provides a practically useful alternative to the state-of-the-art which allows the construction of VLMCs even for very large genomes significantly faster than previously possible. Additionally, our parameter selection based on BIC gives guidance to endusers comparing genomes.
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| 9. |
- Henningsson, Anna, et al.
(författare)
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Human tick-borne encephalitis and characterization of virus from biting tick
- 2016
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 22:8, s. 1485-1487
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Tidskriftsartikel (refereegranskat)abstract
- We report a case of human tick-borne encephalitis (TBE) in which the TBE virus was isolated from the biting tick. Viral growth and sequence were characterized and compared with those of a reference strain. Virus isolation from ticks from patients with TBE may offer a new approach for studies of epidemiology and pathogenicity. © 2016, Centers for Disease Control and Prevention (CDC). All rights reserved.
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| 10. |
- Koelle, D. M., et al.
(författare)
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Worldwide circulation of HSV-2 x HSV-1 recombinant strains
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Homo sapiens harbor two distinct, medically significant species of simplexviruses, herpes simplex virus (HSV)-1 and HSV-2, with estimated divergence 6-8 million years ago (MYA). Unexpectedly, we found that circulating HSV-2 strains can contain HSV-1 DNA segments in three distinct genes. Using over 150 genital swabs from North and South America and Africa, we detected recombinantsworldwide. Common, widely distributed gene UL39 genotypes are parsimoniously explained by an initial >457 basepair (bp) HSV-1 x HSV-2 crossover followed by back-recombination to HSV-2. Blocks of >244 and >539 bp of HSV-1 DNA within genes UL29 and UL30, respectively, have reached near fixation, with a minority of strains retaining sequences we posit as ancestral HSV-2. Our data add to previous in vitroand animal work, implying that in vivo cellular co-infection with HSV-1 and HSV-2 yields viable interspecies recombinants in the natural human host.
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| 11. |
- Liljeqvist, Jan-Åke, 1954, et al.
(författare)
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Asymptomatically shed recombinant herpes simplex virus type 1 strains detected in saliva
- 2009
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 90:Pt 3, s. 559-66
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus type 1 (HSV-1) is a ubiquitous pathogen infecting most individuals worldwide. The majority of HSV-1-infected individuals have no clinical symptoms but shed HSV-1 asymptomatically in saliva. Recent phylogenetic analyses of HSV-1 have defined three genetic clades (A-C) and recombinants thereof. These data have all been based on clinical HSV-1 isolates and do not cover genetic variation of asymptomatically shed HSV-1. The primary goal of this study was to investigate such variation. A total of 648 consecutive saliva samples from five HSV-1-infected volunteers was collected. Asymptomatic shedding was detected on 7.6 % of the days from four subjects. The HSV-1 genome loads were quantified with real-time PCR and varied from 1x10(2) to 2.8x10(6) copies of virus DNA (ml saliva)(-1). Phylogenetic network analyses and bootscanning were performed on asymptomatically shed HSV-1. The analyses were based on DNA sequencing of the glycoprotein I gene, and also of the glycoprotein E gene for putative recombinants. For two individuals with clinical HSV-1 infection, the same HSV-1 strain was shed asymptomatically as induced clinical lesions, and sequence analyses revealed that these strains clustered distinctly to clades A and B, respectively. For one of the subjects with no clinical HSV-1 infection, a recombinant strain was identified. The other truly asymptomatic individual shed evolutionarily distinct HSV-1 strains on two occasions. The first strain was classified as a recombinant and the other strain clustered in clade A. High replication rates of different strains in the same person may facilitate the creation of recombinant clinical HSV-1 strains.
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| 12. |
- Norberg, Peter, 1974, et al.
(författare)
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A genome-wide comparative evolutionary analysis of herpes simplex virus type 1 and varicella zoster virus.
- 2011
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) are closely related viruses causing lifelong infections. They are typically associated with mucocutaneous or skin lesions, but may also cause severe neurological or ophthalmic diseases, possibly due to viral- and/or host-genetic factors. Although these viruses are well characterized, genome-wide evolutionary studies have hitherto only been presented for VZV. Here, we present a genome-wide study on HSV-1. We also compared the evolutionary characteristics of HSV-1 with those for VZV. We demonstrate that, in contrast to VZV for which only a few ancient recombination events have been suggested, all HSV-1 genomes contain mosaic patterns of segments with different evolutionary origins. Thus, recombination seems to occur extremely frequent for HSV-1. We conclude by proposing a timescale for HSV-1 evolution, and by discussing putative underlying mechanisms for why these otherwise biologically similar viruses have such striking evolutionary differences.
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| 13. |
- Norberg, Peter, 1974, et al.
(författare)
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Complete-genome phylogenetic approach to varicella-zoster virus evolution: genetic divergence and evidence for recombination.
- 2006
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Ingår i: Journal of virology. - 0022-538X. ; 80:19, s. 9569-76
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 14. |
- Norberg, Peter, 1974, et al.
(författare)
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Complete Nucleotide Sequence and Analysis of Two Conjugative Broad Host Range Plasmids from a Marine Microbial Biofilm
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- The complete nucleotide sequence of plasmids pMCBF1 and pMCBF6 was determined and analyzed. pMCBF1 and pMCBF6 form a novel clade within the IncP-1 plasmid family designated IncP-1 sigma. The plasmids were exogenously isolated earlier from a marine biofilm. pMCBF1 (62 689 base pairs; bp) and pMCBF6 (66 729 bp) have identical backbones, but differ in their mercury resistance transposons. pMCBF1 carries Tn5053 and pMCBF6 carries Tn5058. Both are flanked by 5 bp direct repeats, typical of replicative transposition. Both insertions are in the vicinity of a resolvase gene in the backbone, supporting the idea that both transposons are "res-site hunters'' that preferably insert close to and use external resolvase functions. The similarity of the backbones indicates recent insertion of the two transposons and the ongoing dynamics of plasmid evolution in marine biofilms. Both plasmids also carry the insertion sequence ISPst1, albeit without flanking repeats. ISPs1is located in an unusual site within the control region of the plasmid. In contrast to most known IncP-1 plasmids the pMCBF1/pMCBF6 backbone has no insert between the replication initiation gene (trfA) and the vegetative replication origin (oriV). One pMCBF1/pMCBF6 block of about 2.5 kilo bases (kb) has no similarity with known sequences in the databases. Furthermore, insertion of three genes with similarity to the multidrug efflux pump operon mexEF and a gene from the NodT family of the tripartite multi-drug resistance-nodulation-division (RND) system in Pseudomonas aeruginosa was found. They do not seem to confer antibiotic resistance to the hosts of pMCBF1/pMCBF6, but the presence of RND on promiscuous plasmids may have serious implications for the spread of antibiotic multi-resistance.
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| 15. |
- Norberg, Peter, 1974
(författare)
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Divergence and genotyping of human alpha-herpesviruses: An overview.
- 2010
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Ingår i: Infection, genetics and evolution. - 1567-1348. ; 10:1, s. 14-25
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Forskningsöversikt (refereegranskat)abstract
- Herpesviruses are large DNA viruses that are highly disseminated among animals. Of the eight herpesviruses identified in humans, three are classified into the α-herpesvirus subfamily: herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), which are typically associated with mucocutaneous lesions, and varicella–zoster virus (VZV), which is the cause of chicken pox and herpes zoster. All three viruses establish lifelong infections and may also induce more severe symptoms, such as neurological manifestations and fatal neonatal infections. Despite thorough investigation of the genetic variability among circulating strains of each virus in recent decades, little is known about possible associations between the genetic setups of the viruses and clinical manifestations in human hosts. This review focuses mainly on evolutionary studies of and genotyping strategies for these three human α-herpesviruses, emphasizing the ambiguities induced by a high frequency of circulating recombinant strains. It also aims to shed light on the challenges of establishing a uniform genotyping strategy for all three viruses.
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| 16. |
- Norberg, Peter, 1974, et al.
(författare)
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Divergence and recombination of clinical herpes simplex virus type 2 isolates.
- 2007
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Ingår i: Journal of virology. - 1098-5514. ; 81:23, s. 13158-67
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Forskningsöversikt (refereegranskat)abstract
- Herpes simplex virus type 2 (HSV-2) infects the genital mucosa and is one of the most common sexually transmitted viruses. Here we sequenced a segment comprising 3.5% of the HSV-2 genome, including genes coding for glycoproteins G, I, and E, from 27 clinical isolates from Tanzania, 10 isolates from Norway, and 10 isolates from Sweden. The sequence variation was low compared to that described for clinical HSV-1 isolates, with an overall similarity of 99.6% between the two most distant HSV-2 isolates. Phylogenetic analysis revealed a divergence into at least two genogroups arbitrarily designated A and B, supported by high bootstrap values and evolutionarily separated at the root. Genogroup A contained isolates collected in Tanzania, and genogroup B contained isolates collected in Tanzania and Scandinavia, implying that the genetic variability of HSV-2 is higher in Tanzania than in Scandinavia. Recombination network analysis and bootscan analysis revealed a complex pattern of phylogenetically conflicting informative sites in the sequence alignments. These signals were present in synonymous and nonsynonymous sites in all three genes and were not accumulated in specific regions, observations arguing against positive selection. Since the PHI test applied solely to synonymous sites revealed a high statistical probability of recombination, we suggest as a novel finding that homologous recombination is, as reported earlier for HSV-1 and varicella-zoster virus, a prominent feature in the evolution of HSV-2.
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| 17. |
- Norberg, Peter, 1974
(författare)
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Evolution of human alpha-herpesviruses
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Herpesviridae is a large virus family with more than 100 members, which are highly disseminated among animals. Three sub-families have been classified; alpha-herpesviruses, beta-herpesviruses and gamma-herpesviruses. Eight herpesviruses have hitherto been identified in humans of which three belong to the alpha-herpesviruses; (i) herpes simplex virus type 1 (HSV-1), which is a ubiquitous pathogen causing mainly oral or genital lesions, (ii) herpes simplex virus type 2 (HSV-2), which is closely related to HSV-1, and is the most common sexually transmitted virus globally, causing mainly genital lesions, and (iii) Varicella zoster virus (VZV), which is the cause of chicken pox and shingles. All alpha-herpesviruses give lifelong infections and establish latency in the sensory ganglia. In the present work, the genetic variability of clinical HSV-1, HSV-2 and VZV isolates was investigated. Twenty-eight clinical HSV-1 isolates were collected from patients suffering from oral or genital lesions or encephalitis and compared with the laboratory strains F, KOS321 and 17. Phylogenetic analyses based on the genes US4, US7 and US8 divided the isolates into three genogroups, arbitrarily designated as A, B and C, differing in DNA sequences by approximately 2%. In addition, seven clinical isolates as well as strain 17 were classified as recombinants. To facilitate further genotyping of clinical isolates an assay was developed based on restriction enzyme cleavage of PCR-products. Furthermore, a polymorphic tandem repeat (TR) region was detected in US7. The region encodes the amino acids serine, threonine and proline, which are targets for O-linked glycosylation. Using a synthetic peptide, containing two of the repeated blocks, it was shown that the described TR-region is a substrate for massive O-linked glycosylation, and hence codes for a mucin region. Mucin regions have not been described previously within herpesvirus-encoded proteins. The corresponding genes were sequenced and investigated for 45 clinical HSV-2 isolates collected in Sweden, Norway and Tanzania. Phylogenetic analysis revealed a divergence of the isolates in one Tanzanian and one European genogroup, arbitrarily designated as A and E, differing by approximately 0.4%. In addition, analyses using recombination networks, the BootsScan method and the phi-test, suggested that most HSV-2 isolates are mosaic recombinants. The complete genome was sequenced for two VZV isolates and compared with the laboratory strains MSP, Dumas, BR, p-Oka and the vaccine strain v-Oka. The results show a division of VZV into four genogroups, designated as E, J, M1 and M2, of which M1 and M2 were suggested to be recombinants derived from ancient recombination events between viruses from the E and J genogroups. In conclusion, the results presented here demonstrate that clinical isolates, for all three investigated human alpha-herpesviruses, can be divided into different genogroups. Estimations of evolutionary timescales suggest that the divergence of the three HSV-1 genogroups may have occurred approximately 500,000 Myears BP, i.e. prior to the emergence of Homo sapiens. Furthermore, it is evident that intrastrain recombination is a prominent feature of the evolutionary history of these viruses. Thus, homologous recombination is suggested to be a powerful evolutionary mechanism for human alpha-herpesviruses to exchange genetic segments between different viral strains, as well as to create variability of TR-regions.
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| 18. |
- Norberg, Peter, 1974, et al.
(författare)
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Genetic recombination of tick-borne flaviviruses among wild-type strains
- 2013
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Ingår i: Virology. - : Elsevier BV. - 0042-6822. ; 440:2, s. 105-116
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Tidskriftsartikel (refereegranskat)abstract
- Genetic recombination has been suggested to occur in mosquito-borne flaviviruses. In contrast, tick-borne flaviviruses have been thought to evolve in a clonal manner, although recent studies suggest that recombination occurs also for these viruses. We re-analyzed the data and found that previous conclusions on wild type recombination were probably falsely drawn due to misalignments of nucleotide sequences, ambiguities in GenBank sequences, or different laboratory culture histories suggestive of recombination events in laboratory. To evaluate if reliable predictions of wild type recombination of tick-borne flaviviruses can be made, we analyzed viral strains sequenced exclusively for this study, and other flavivirus sequences retrieved from GenBank. We detected genetic signals supporting recombination between viruses within the three clades of TBEV-Eu, TBEV-Sib and TBEV-Fe, respectively. Our results suggest that the tick-borne encephalitis viruses may undergo recombination under natural conditions, but that geographic barriers restrict most recombination events to involve only closely genetically related viruses.
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| 19. |
- Norberg, Peter, 1974, et al.
(författare)
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Genotyping of clinical herpes simplex virus type 1 isolates by use of restriction enzymes.
- 2006
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Ingår i: Journal of clinical microbiology. - 0095-1137. ; 44:12, s. 4511-4
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Tidskriftsartikel (refereegranskat)abstract
- Recently, three distinct genotypes of clinical herpes simplex virus type 1 (HSV-1) isolates were identified based on DNA sequence information and phylogenetic analysis of clinical isolates and laboratory strains. We utilized single-nucleotide polymorphism within the genes coding for glycoproteins G and I for rapid genotype classification by PCR and restriction enzyme cleavage. The method is suitable for high-scale genotyping of clinical HSV-1 isolates and for the detection of recombinants.
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| 20. |
- Norberg, Peter, 1974, et al.
(författare)
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Glycoprotein I of herpes simplex virus type 1 contains a unique polymorphic tandem-repeated mucin region.
- 2007
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 88:Pt 6, s. 1683-8
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Forskningsöversikt (refereegranskat)abstract
- Glycoprotein I (gI) of herpes simplex virus type 1 (HSV-1) contains a tandem repeat (TR) region including the amino acids serine and threonine, residues that can be utilized for O-glycosylation. The length of this TR region was determined for 82 clinical HSV-1 isolates and the results revealed a polymorphic distribution of two to six or eight repeated blocks with a majority harbouring between two and four repeats. Assessment of the O-glycosylation capacity of an acceptor peptide (STPSTTTSTPSTTT), representing two of the gI blocks, showed that the peptide was a universal substrate for O-glycosylation not only for the two most commonly expressed N-acetyl-d-galactosamine (GalNAc)-T1 and -T2 transferases, but also for the GalNAc-T3, -T4 and -T11 transferases. Immunoblotting of virus-infected cells showed that gI was exclusively O-glycosylated with GalNAc monosaccharides (Tn antigen). A polymorphic mucin region has not been described previously for HSV-1 and is a unique finding, as repeated blocks within gI homologues are lacking in other alphaherpesviruses.
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| 21. |
- Norberg, Peter, 1974, et al.
(författare)
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Phylogenetic analysis of clinical herpes simplex virus type 1 isolates identified three genetic groups and recombinant viruses.
- 2004
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Ingår i: Journal of virology. - 0022-538X. ; 78:19, s. 10755-64
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus type 1 (HSV-1) is a ubiquitous human pathogen which establishes lifelong infections. In the present study, we determined the sequence diversity of the complete genes coding for glycoproteins G (gG), I (gI), and E (gE), comprising 2.3% of the HSV-1 genome and located within the unique short (US) region, for 28 clinical HSV-1 isolates inducing oral lesions, genital lesions, or encephalitis. Laboratory strains F and KOS321 were sequenced in parallel. Phylogenetic analysis, including analysis of laboratory strain 17 (GenBank), revealed that the sequences were separated into three genetic groups. The identification of different genogroups facilitated the detection of recombinant viruses by using specific nucleotide substitutions as recombination markers. Seven of the isolates and strain 17 displayed sequences consistent with intergenic recombination, and at least four isolates were intragenic recombinants. The observed frequency of recombination based on an analysis of a short stretch of the US region suggests that most full-length HSV-1 genomes consist of a mosaic of segments from different genetic groups. Polymorphic tandem repeat regions, consisting of two to eight blocks of 21 nucleotides in the gI gene and seven to eight repeats of 3 nucleotides in the gG gene, were also detected. Laboratory strain KOS321 displayed a frameshift mutation in the gI gene with a subsequent alteration of the deduced intracellular portion of the protein. The presence of polymorphic tandem repeat regions and the different genogroup identities can be used for molecular epidemiology studies and for further detection of recombination in the HSV-1 genome.
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| 22. |
- Norberg, Peter, 1974
(författare)
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Prevalence of herpes simplex virus type 1 glycoprotein G (gG) and gI genotypes in patients with herpetic keratitis.
- 2008
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Ingår i: The british journal of ophthalmology. - : BMJ. - 0007-1161. ; 92:9, s. 1195-200
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Recent phylogenetic analyses on the herpes simplex virus type 1 (HSV-1) genes US4, encoding glycoprotein G (gG) and US7, encoding gI, of clinical HSV-1 isolates have led to the classification of HSV-1 into three genotypes, arbitrarily designated as A, B and C. The prevalence of the HSV-1 gG and gI genotypes and their potential disease association was determined in a large cohort of patients with herpetic keratitis (HK). METHODS: Primary corneal HSV-1 isolates of 178 HK patients were genotyped by a PCR-based restriction fragment length polymorphism method targeting the viral genes US4 and US7. RESULTS: Genotype B was more frequently expressed by the corneal HSV-1 isolates compared with genotypes A and C. Fifty-five of 178 corneal isolates (31%) had different genotypes in both loci. No clinically relevant associations were observed between the HSV-1 genotypes and disease outcome in the HK patients studied. CONCLUSIONS: The data presented demonstrate a high frequency of recombinant corneal HSV-1 isolates and suggest that clinical outcome of HSV-1-induced keratitis is independent of a gG or gI genotype.
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| 23. |
- Norberg, Peter, 1974, et al.
(författare)
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Published sequences do not support transfer of oseltamivir resistance mutations from avian to human influenza A virus strains
- 2015
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Ingår i: Bmc Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tamiflu (oseltamivir phosphate ester, OE) is a widely used antiviral active against influenza A virus. Its active metabolite, oseltamivir carboxylate (OC), is chemically stable and secreted into wastewater treatment plants. OC contamination of natural habitats of waterfowl might induce OC resistance in influenza viruses persistently infecting waterfowl, and lead to transfer of OC-resistance from avian to human influenza. The aim of this study was to evaluate whether such has occurred. Methods: A genomics approach including phylogenetic analysis and probability calculations for homologous recombination was applied on altogether 19,755 neuraminidase (N1 and N2) genes from virus sampled in humans and birds, with and without resistance mutations. Results: No evidence for transfer of OE resistance mutations from avian to human N genes was obtained, and events suggesting recombination between human and avian influenza virus variants could not be traced in the sequence material studied. Conclusions: The results indicate that resistance in influenza viruses infecting humans is due to the selection pressure posed by the global OE administration in humans rather than transfer from avian influenza A virus strains carrying mutations induced by environmental exposure to OC.
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| 24. |
- Norberg, Peter, 1974, et al.
(författare)
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Recombination of Globally Circulating Varicella-Zoster Virus
- 2015
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Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 89:14, s. 7133-7146
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Tidskriftsartikel (refereegranskat)abstract
- Varicella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide. Recent studies of another alphaherpesvirus, infectious laryngotracheitis virus, demonstrate that live-attenuated vaccine strains can recombine in vivo, creating virulent progeny. These findings raised concerns about using attenuated herpesvirus vaccines under conditions that favor recombination. To investigate whether VZV may undergo recombination, which is a prerequisite for VZV vaccination to create such conditions, we here analyzed 115 complete VZV genomes. Our results demonstrate that recombination occurs frequently for VZV. It thus seems that VZV is fully capable of recombination if given the opportunity, which may have important implications for continued VZV vaccination. Although no interclade vaccine-wild-type recombinant strains were found, intraclade recombinants were frequently detected in clade 2, which harbors the vaccine strains, suggesting that the vaccine strains have already been involved in recombination events, either in vivo or in vitro during passages in cell culture. Finally, previous partial and complete genomic studies have described strains that do not cluster phylogenetically to any of the five established clades. The additional VZV strains sequenced here, in combination with those previously published, have enabled us to formally define a novel sixth VZV clade. Although genetic recombination has been demonstrated to frequently occur for other human alphaherpesviruses, herpes simplex viruses 1 and 2, only a few ancient and isolated recent recombination events have hitherto been demonstrated for VZV. In the present study, we demonstrate that VZV also frequently undergoes genetic recombination, including strains belonging to the clade containing the vOKA strain.
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| 25. |
- Norberg, Peter, 1974, et al.
(författare)
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The IncP-1 plasmid backbone adapts to different host bacterial species and evolves through homologous recombination.
- 2011
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Plasmids are important members of the bacterial mobile gene pool, and are among the most important contributors to horizontal gene transfer between bacteria. They typically harbour a wide spectrum of host beneficial traits, such as antibiotic resistance, inserted into their backbones. Although these inserted elements have drawn considerable interest, evolutionary information about the plasmid backbones, which encode plasmid related traits, is sparse. Here we analyse 25 complete backbone genomes from the broad-host-range IncP-1 plasmid family. Phylogenetic analysis reveals seven clades, in which two plasmids that we isolated from a marine biofilm represent a novel clade. We also found that homologous recombination is a prominent feature of the plasmid backbone evolution. Analysis of genomic signatures indicates that the plasmids have adapted to different host bacterial species. Globally circulating IncP-1 plasmids hence contain mosaic structures of segments derived from several parental plasmids that have evolved in, and adapted to, different, phylogenetically very distant host bacterial species.
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| 26. |
- Tang, Ka-Wei, 1983, et al.
(författare)
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Rad51 and rad52 are involved in homologous recombination of replicating herpes simplex virus DNA.
- 2014
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Replication of herpes simplex virus 1 is coupled to recombination, but the molecular mechanisms underlying this process are poorly characterized. The role of Rad51 and Rad52 recombinases in viral recombination was examined in human fibroblast cells 1BR.3.N (wild type) and in GM16097 with replication defects caused by mutations in DNA ligase I. Intermolecular recombination between viruses, tsS and tsK, harboring genetic markers gave rise to ∼17% recombinants in both cell lines. Knock-down of Rad51 and Rad52 by siRNA reduced production of recombinants to 11% and 5%, respectively, in wild type cells and to 3% and 5%, respectively, in GM16097 cells. The results indicate a specific role for Rad51 and Rad52 in recombination of replicating herpes simplex virus 1 DNA. Mixed infections using clinical isolates with restriction enzyme polymorphisms in the US4 and US7 genes revealed recombination frequencies of 0.7%/kbp in wild type cells and 4%/kbp in GM16097 cells. Finally, tandem repeats in the US7 gene remained stable upon serial passage, indicating a high fidelity of recombination in infected cells.
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| 27. |
- Thomsen, M. M., et al.
(författare)
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Genetic Variants and Immune Responses in a Cohort of Patients With Varicella Zoster Virus Encephalitis
- 2021
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 224:12, s. 2122-2132
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Tidskriftsartikel (refereegranskat)abstract
- Background. Infection with varicella zoster virus (VZV) may involve different central nervous system (CNS) manifestations, including meningitis, encephalitis, and vasculitis. In cases in which otherwise healthy individuals are affected, an inborn error of immunity may underlie increased susceptibility or severity of infection. Methods. We collected a cohort of 17 adults who experienced VZV encephalitis and performed whole exome sequencing. Patient peripheral blood mononuclear cells were infected with VZV, and innate antiviral interferon (IFN) and cytokine responses as well as viral replication were evaluated. Data were analyzed by Mann-Whitney U test. Results. We identified a total of 21 different potentially disease-causing variants in a total of 13 of the 17 patients included. These gene variants were within 2 major functional clusters: (1) innate viral sensors and immune pathways and (2) autophagy pathways. Antiviral IFN and cytokine responses were abnormal in the majority of patients, whereas viral replication was increased in only 2 of 17 patients. Conclusions. This study identifies a list of variants of pathogenic potential, which may serve as a platform for generating hypotheses for future studies addressing genetic and immunological factors associated with susceptibility to VZV encephalitis. These data, taken together, suggest that disturbances in innate sensing and autophagy pathways may predispose to VZV encephalitis.
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| 28. |
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| 29. |
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| 30. |
- Ögren, Petter, 1974-, et al.
(författare)
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Design and implementation of a new teleoperation control mode for differential drive UGVs
- 2014
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Ingår i: Autonomous Robots. - : Springer Science and Business Media LLC. - 0929-5593 .- 1573-7527. ; 37:1, s. 71-79
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we propose and implement a new control mode for teleoperated unmanned ground vehicles (UGVs), that exploits the similarities between computer games and teleoperation robotics. Today, all teleoperated differential drive UGVs use a control mode called Tank Control, in which the UGV chassis and the pan tilt camera are controlled separately. This control mode was also the dominating choice when the computer game genre First Person Shooter (FPS) first appeared. However, the hugely successful FPS genre, including titles such as Doom, Half Life and Call of Duty, now uses a much more intuitive control mode, Free Look Control (FLC), in which rotation and translation of the character are decoupled, and controlled separately. The main contribution of this paper is that we replace Tank Control with FLC in a real UGV. Using feedback linearization, the orientation of the UGV chassis is abstracted away, and the orientation and translation of the camera are decoupled, enabling the operator to use FLC when controlling the UGV. This decoupling is then experimentally verified. The developments in the gaming community indicates that FLC is more intuitive than Tank Control and reduces the well known situational awareness problem. It furthermore reduces the need for operator training, since literary millions of future operators have already spent hundreds of hours using the interface.
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