| 1. |
- Fallesen, Peter, et al.
(författare)
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The Effect of Medical Treatment of Attention Deficit Hyperactivity Disorder (ADHD) on Foster Care Caseloads : Evidence from Danish Registry Data
- 2015
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Ingår i: Journal of health and social behavior. - : SAGE Publications. - 0022-1465 .- 2150-6000. ; 56:3, s. 398-414
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Tidskriftsartikel (refereegranskat)abstract
- Since the early 2000s, foster care caseloads have decreased in many wealthy democracies, yet the causes of these declines remain, for the most part, a mystery. This article uses administrative data on all Danish municipalities (N = 277) and a 10% randomly drawn sample of all Danish children (N = 157,938) in the period from 1998 to 2010 to show that increasing medical treatment of attention deficit hyperactivity disorder (ADHD) accounts for a substantial share of the decrease in foster care caseloads. According to our estimates, the decline in foster care caseloads during this period would have been 45% smaller absent increases in medical treatment of ADHD. These findings are especially provocative in light of recent research showing ambiguous effects of medical treatment of ADHD. Future research should be attentive to how medical treatment aimed at addressing children's acute behavioral problems could also have a powerful effect on foster care caseloads.
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| 2. |
- Ahlen, Gustaf, et al.
(författare)
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Limited effect on NS3-NS4A protein cleavage after alanine substitutions within the immunodominant HLA-A2-restricted epitope of the hepatitis C virus genotype 3a non-structural 3/4A protease.
- 2012
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 93:Pt 8, s. 1680-1686
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Tidskriftsartikel (refereegranskat)abstract
- It has been well established that immunological escape mutations within the hepatitis C virus genotype (gt) 1a non-structural (NS) 3/4A protease is partly prevented by a reduction of the viral protease fitness. Surprisingly little is known whether similar mutations affect proteases from other genotypes. In the present study, we assessed both the human leukocyte antigen (HLA)-A2-restricted cytotoxic T cell response and gt3a NS3/4A protease fitness. Similar to gt1, the 1073-1081 epitope was also immunodominant within the gt3a-specific HLA-A2-restricted cytotoxic T cell response, despite a homology of only 56% between gt1a and gt3a genes. However, unlike the gt1a NS3/4A protease, all residues within the gt3a 1073-1081 epitope could sequentially be replaced by alanine with a, at least in part, retained protease activity.
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| 3. |
- Anderson, Jennifer L, et al.
(författare)
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Outcrossing and the maintenance of males within C. elegans populations.
- 2010
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Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 101 Suppl 1
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Tidskriftsartikel (refereegranskat)abstract
- Caenorhabditis elegans is an androdioecious nematode with both hermaphrodites and males. Although males can potentially play an important role in avoiding inbreeding and facilitating adaptation, their existence is evolutionarily problematic because they do not directly generate offspring in the way that hermaphrodites do. This review explores how genetic, population genomic, and experimental evolution approaches are being used to address the role of males and outcrossing within C. elegans. Although theory suggests that inbreeding depression and male mating ability should be the primary determinants of male frequency, this has yet to be convincingly confirmed experimentally. Genomic analysis of natural populations finds that outcrossing occurs at low, but not negligible levels, and that observed patterns of linkage disequilibrium consistent with strong selfing may instead be generated by natural selection against outcrossed progeny. Recent experimental evolution studies suggest that males can be maintained at fairly high levels if populations are initiated with sufficient genetic variation and/or subjected to strong natural selection via a change in the environment. For example, as reported here, populations adapting to novel laboratory rearing and temperature regimes maintain males at frequencies from 5% to 40%. Laboratory and field results still await full reconciliation, which may be facilitated by identifying the loci underlying among-strain differences in mating system dynamics.
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| 4. |
- Andersson, Stefan, et al.
(författare)
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Quantitative genetic effects of bottlenecks : experimental evidence from a wild plant species, Nigella degenii
- 2010
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Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 101:3, s. 298-307
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the genetic consequences of changes in population size is fundamental in a variety of contexts, such as adaptation and conservation biology. In the study presented here, we have performed a replicated experiment with the plant Nigella degenii to explore the quantitative genetic effects of a single-founder bottleneck. In agreement with adetive theory, the bottleneck reduced the mean (co)variance within lines and caused stochastic, line-specific changes in the genetic (co)variance structure. However, a significant portion of the (co)variance structure was conserved, and 2 characters—leaf and flower (sepal) size—turned out to be positively correlated in all data sets, indicating a potential for correlated evolution in these characters, even after a severe bottleneck. The hierarchical partitioning of genetic variance for flower size was in good agreement with predictions from additive theory, whereas the remaining characters showed an excess of within-line variance and a deficiency of among-line variance. The latter discrepancies were most likely a result of selection, given the small proportion of lines (23%) that remained viable until the end of the experiment. Our results suggest that bottlenecked populations of N. degenii generally have a lower adaptive potential than the ancentral population but also highlight the idiosyncratic nature of bottleneck effects.
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| 5. |
- Asghar, Naveed, et al.
(författare)
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Deep sequencing analysis of tick-borne encephalitis virus from questing ticks at natural foci reveals similarities between quasispecies pools of the virus
- 2017
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Ingår i: Journal of General Virology. - : The Microbiology Society. - 0022-1317 .- 1465-2099. ; 98:3, s. 413-421
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Tidskriftsartikel (refereegranskat)abstract
- Every year, tick-borne encephalitis virus (TBEV) causes severe central nervous system infection in 10 000 to 15 000 people in Europe and Asia. TBEV is maintained in the environment by an enzootic cycle that requires a tick vector and a vertebrate host, and the adaptation of TBEV to vertebrate and invertebrate environments is essential for TBEV persistence in nature. This adaptation is facilitated by the error-prone nature of the virus's RNA-dependent RNA polymerase, which generates genetically distinct virus variants called quasispecies. TBEV shows a focal geographical distribution pattern where each focus represents a TBEV hotspot. Here, we sequenced and characterized two TBEV genomes, JP-296 and JP-554, from questing Ixodes ricinus ticks at a TBEV focus in central Sweden. Phylogenetic analysis showed geographical clustering among the newly sequenced strains and three previously sequenced Scandinavian strains, Toro-2003, Saringe-2009 and Mandal-2009, which originated from the same ancestor. Among these five Scandinavian TBEV strains, only Mandal-2009 showed a large deletion within the 3' non-coding region (NCR), similar to the highly virulent TBEV strain Hypr. Deep sequencing of JP-296, JP-554 and Mandal-2009 revealed significantly high quasispecies diversity for JP-296 and JP-554, with intact 3' NCRs, compared to the low diversity in Mandal-2009, with a truncated 3' NCR. Single-nucleotide polymorphism analysis showed that 40% of the single-nucleotide polymorphisms were common between quasispecies populations of JP-296 and JP-554, indicating a putative mechanism for how TBEV persists and is maintained within its natural foci.
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| 6. |
- Ayukekbong, James, et al.
(författare)
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Role of noroviruses as aetiological agents of diarrhoea in developing countries
- 2015
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 96, s. 1983-1999
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Tidskriftsartikel (refereegranskat)abstract
- Diarrhoea is considered to be the second leading cause of death due to infections among children <5 years of age worldwide that may be caused by bacteria, parasites, viruses and non-infectious agents. The major causative agents of diarrhoea in developing countries may vary from those in developed countries. Noroviruses are considered to be the most common cause of acute diarrhoea in both children and adults in industrialized countries. On the other hand, there is a lack of comprehensive epidemiological evidence from developing countries that norovirus is a major cause of diarrhoea. In these regions, asymptomatic norovirus infections are very common, and similar detection rates have been observed in patients with diarrhoea and asymptomatic persons. This review summarizes the current knowledge of norovirus infection in developing countries and seeks to position infections with noroviruses among those of other enteropathogens in terms of disease burden in these regions.
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| 7. |
- Barqasho, Babilonia, et al.
(författare)
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Implications of the release of high-mobility group box 1 protein from dying cells during human immunodeficiency virus type 1 infection in vitro
- 2010
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 91:Pt 7, s. 1800-1809
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Tidskriftsartikel (refereegranskat)abstract
- Plasma levels of high-mobility group box 1 protein (HMGB1) are elevated during the course of human immunodeficiency virus type 1 (HIV-1) infection and the molecule has an impact on virus replication. This study investigated the mode of cell death and release of HMGB1 during HIV-1 infection in vitro. MT4 cells and primary CD4(+) T cells were infected with HIV-1 isolates, and HMGB1 release was monitored in relation to cytopathic effects (CPE) and apoptosis. HMGB1 release from cells was analysed by Western blotting. For MT4 cells, an enzyme-linked immunosorbent spot (ELISPOT) assay was adapted to measure the release during necrosis. Lactate dehydrogenase (LDH) activity was quantified using a commercial assay. Flow cytometry was used to determine the level of infection and apoptosis. MT4 cells were > or =90 % infected at 48 h post-infection (p.i.). CPE was first observed at 60 h and correlated with release of HMGB1, LDH activity and caspase-3 (C3) activation. HMGB1 spots were clearly detected by ELISPOT assay at 72 h p.i. Annexin V and C3 staining showed that apoptosis was substantially involved in HIV-1-related cell death. Addition of Z-VAD (a caspase inhibitor) in a single dose at 24 or 40 h p.i. decreased both the number of caspase-positive cells and the release of HMGB1. Infection of primary CD4(+) T cells showed a 22 % (median) infection rate at 96 h. Related CPE corresponded to LDH and HMGB1 release. Both necrosis and apoptosis contributed to HMGB1 liberation during HIV-1-induced cell death and the protein could induce tumour necrosis factor-alpha release from peripheral mononuclear blood cells. These data imply that passive HMGB1 release contributes to the excessive immune activation characteristic of HIV-1 pathogenesis.
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| 8. |
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| 9. |
- Bidokhti, Mehdi, et al.
(författare)
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Evolutionary dynamics of bovine coronaviruses: natural selection pattern of the spike gene implies adaptive evolution of the strains
- 2013
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 94, s. 2036-2049
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Tidskriftsartikel (refereegranskat)abstract
- Coronaviruses demonstrate great potential for interspecies transmission, including zoonotic outbreaks. Although bovine coronavirus (BCoV) strains are frequently circulating in cattle farms worldwide, causing both enteric and respiratory disease, little is known about their genomic evolution. We sequenced and analysed the full-length spike (S) protein gene of 33 BCoV strains from dairy and feedlot farms collected during outbreaks that occurred from 2002 to 2010 in Sweden and Denmark. Amino acid identities were >97% for the BCoV strains analysed in this work. These strains formed a clade together with Italian BCoV strains and were highly similar to human enteric coronavirus HECV-4408/US/94. A high similarity was observed between BCoV, canine respiratory coronavirus (CRCoV) and human coronavirus OC43 (HCoV-OC43). Molecular clock analysis of the S gene sequences estimated BCoV and CRCoV diverged from a common ancestor in 1951, while the time of divergence from a common ancestor of BCoV and HCoV-OC43 was estimated to be 1899. BCoV strains showed the lowest similarity to equine coronavirus, placing the date of divergence at the end of the eighteenth century. Two strongly positive selection sites were detected along the receptor-binding subunit of the S protein gene: spanning amino acid residues 109-131 and 495-527. By contrast, the fusion subunit was observed to be under negative selection. The selection pattern along the S glycoprotein implies adaptive evolution of BCoVs, suggesting a successful mechanism for BCoV to continuously circulate among cattle and other ruminants without disappearance.
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| 10. |
- Blomström, Anne-Lie
(författare)
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NSs protein of Schmallenberg virus counteracts the antiviral response of the cell by inhibiting its transcriptional machinery
- 2014
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 95, s. 1640-1646
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Tidskriftsartikel (refereegranskat)abstract
- Bunyaviruses have evolved a variety of strategies to counteract the antiviral defence systems of mammalian cells. Here we show that the NSs protein of Schmallenberg virus (SBV) induces the degradation of the RPB1 subunit of RNA polymerase II and consequently inhibits global cellular protein synthesis and the antiviral response. In addition, we show that the SBV NSs protein enhances apoptosis in vitro and possibly in vivo, suggesting that this protein could be involved in SBV pathogenesis in different ways.
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| 11. |
- Boreström, Cecilia, 1974, et al.
(författare)
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E2F1, ARID3A/Bright and Oct-2 factors bind to the Epstein-Barr virus C promoter, EBNA1 and oriP, participating in long-distance promoter-enhancer interactions.
- 2012
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 93, s. 1065-75
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Tidskriftsartikel (refereegranskat)abstract
- The Epstein-Barr virus (EBV) C promoter (Cp) regulates several genes required for B-cell proliferation in latent EBV infection. The family of repeats (FR) region of the latent origin of plasmid replication (oriP) functions as an Epstein-Barr nuclear antigen 1 (EBNA1)-dependent distant enhancer of Cp activity, and the enhancer-promoter interaction is mediated by a higher-order multi-protein complex containing several copies of EBNA1. Using DNA-affinity purification with a 170 bp region of the Cp in combination with mass spectrometry, we identified the cell cycle-regulatory protein E2F1, the E2F-binding protein ARID3A, and the B-cell-specific transcription factor Oct-2 as components of this multi-protein complex. Binding of the three factors to the FR region of oriP was determined by DNA-affinity and immunoblot analysis. Co-immunoprecipitation and proximity ligation analysis revealed that the three factors, E2F1, ARID3A and Oct-2, interact with each other as well as with EBNA1 in the nuclei of EBV-positive cells. Using the chromatin immunoprecipitation assay, we showed that E2F1 and Oct-2 interacted with the FR part of oriP and the Cp, but the ARID3A interaction was, however, only detected at the Cp. Our findings support the hypothesis that EBNA1 initiates transcription at the Cp via interactions between multiple EBNA1 homodimers and cellular transcription factors in a large molecular machinery that forms a dynamic interaction between Cp and FR.
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| 12. |
- Borggren, Marie, et al.
(författare)
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R5 human immunodeficiency virus type 1 with efficient DC-SIGN use is not selected for early after birth in vertically infected children
- 2013
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 94:Pt 4, s. 767-773
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Tidskriftsartikel (refereegranskat)abstract
- The binding of human immunodeficiency virus (HIV) to C-type lectin receptors may result in either enhanced trans-infection of T-cells or virus degradation. We have investigated the efficacy of HIV-1 utilization of DC-SIGN, a C-type lectin receptor, in the setting of intrauterine or intrapartum mother-to-child transmission (MTCT). Viruses isolated from HIV-1-infected mothers at delivery and from their vertically infected children both shortly after birth and later during the progression of the disease were analysed for their use of DC-SIGN, binding and ability to trans-infect. DC-SIGN use of a child’s earlier virus isolate tended to be reduced as compared with that of the corresponding maternal isolate. Furthermore, the children’s later isolate displayed enhanced DC-SIGN utilization compared with that of the corresponding earlier virus. These results were also supported in head-to-head competition assays and suggest that HIV-1 variants displaying efficient DC-SIGN use are not selected for during intrauterine or intrapartum MTCT. However, viruses with increased DC-SIGN use may evolve later in paediatric HIV-1 infections.
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| 13. |
- 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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| 14. |
- Chen, Zhiqiang, et al.
(författare)
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Increased Prediction Ability in Norway Spruce Trials Using a Marker X Environment Interaction and Non-Additive Genomic Selection Model
- 2019
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Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 110, s. 830-843
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Tidskriftsartikel (refereegranskat)abstract
- A genomic selection study of growth and wood quality traits is reported based on control-pollinated Norway spruce families established in 2 Northern Swedish trials at 2 locations using exome capture as a genotyping platform. Nonadditive effects including dominance and first-order epistatic interactions (including additive-by-additive, dominance-by-dominance, and additive-by-dominance) and marker-by-environment interaction (MxE) effects were dissected in genomic and phenotypic selection models. Genomic selection models partitioned additive and nonadditive genetic variances more precisely than pedigree-based models. In addition, predictive ability in GS was substantially increased by including dominance and slightly increased by including MxE effects when these effects are significant. For velocity, response to genomic selection per year increased up to 78.9/80.8%, 86.9/82.9%, and 91.3/88.2% compared with response to phenotypic selection per year when genomic selection was based on 1) main marker effects (M), 2) M + MxE effects (A), and 3) A + dominance effects (AD) for sites 1 and 2, respectively. This indicates that including MxE and dominance effects not only improves genetic parameter estimates but also when they are significant may improve the genetic gain. For tree height, Pilodyn, and modulus of elasticity (MOE), response to genomic selection per year improved up to 68.9%, 91.3%, and 92.6% compared with response to phenotypic selection per year, respectively.
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| 15. |
- Duffy, Margaret R., et al.
(författare)
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Generation and characterization of a novel candidate gene therapy and vaccination vector based on human species D adenovirus type 56
- 2018
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 99, s. 135-147
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Tidskriftsartikel (refereegranskat)abstract
- The vectorization of rare human adenovirus (HAdV) types will widen our knowledge of this family and their interaction with cells, tissues and organs. In this study we focus on HAdV-56, a member of human Ad species D, and create ease-of-use cloning systems to generate recombinant HAdV-56 vectors carrying foreign genes. We present in vitro transduction profiles for HAdV-56 in direct comparison to the most commonly used HAdV-5-based vector. In vivo characterizations demonstrate that when it is delivered intravenously (i.v.) HAdV-56 mainly targets the spleen and, to a lesser extent, the lungs, whilst largely bypassing liver transduction in mice. HAdV-56 triggered robust inflammatory and cellular immune responses, with higher induction of IFNγ, TNFα, IL5, IL6, IP10, MCP1 and MIG1 compared to HAdV-5 following i.v. administration. We also investigated its potential as a vaccine vector candidate by performing prime immunizations in mice with HAdV-56 encoding luciferase (HAdV-56-Luc). Direct comparisons were made to HAdV-26, a highly potent human vaccine vector currently in phase II clinical trials. HAdV-56-Luc induced luciferase 'antigen'-specific IFNγ-producing cells and anti-HAdV-56 neutralizing antibodies in Balb/c mice, demonstrating a near identical profile to that of HAdV-26. Taken together, the data presented provides further insight into human Ad receptor/co-receptor usage, and the first report on HAdV-56 vectors and their potential for gene therapy and vaccine applications.
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| 16. |
- Faust, Helena, et al.
(författare)
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Mutations in human papillomavirus type 16 L1 hypervariable surface-exposed loops affect L2 binding and DNA encapsidation
- 2013
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 94:Pt 8, s. 1841-1849
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Tidskriftsartikel (refereegranskat)abstract
- Prophylactic vaccines against human papillomavirus (HPV) based on virus-like particles (VLP) induce type-specific neutralizing antibodies against a small number of hypervariable residues positioned in surface-exposed loops of the major capsid protein L1. To investigate the importance of these residues for neutralization, cross-neutralization, L2 incorporation and genome encapsidation, ten surface-exposed amino acid residues in four hypervariable loops of L1 were mutated. VLPs containing mutated or WT L1, with or without WT L2, were produced in 293TT cells using pseudovirion expression vectors. The mutations reduced the ability to induce neutralizing antibodies and to incorporate the L2 protein in the capsid. Ability to induce cross-neutralizing antibodies and to encapsidate pseudogenomes were completely abrogated. In summary, the surface-exposed L1 loops are important for the function of the HPV particle.
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| 17. |
- Faust, Helena, et al.
(författare)
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Prevalence of human papillomavirus types, viral load and physical status of HPV16 in head and neck squamous cell carcinoma from the South Swedish Health Care Region
- 2016
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 97:11, s. 2949-2956
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Tidskriftsartikel (refereegranskat)abstract
- Incidence of human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is rising in several countries. Intriguingly, large variations of HPV16 viral load and different proportions of the physical viral status among HNSCC have been reported. We analysed fresh biopsies of 275 HNSCC patients from the South Swedish Health Care Region for HPV types with modified general primer PCR and Luminex. Seventy-eight HPV16-positive HNSCC cases were further investigated for viral DNA load and physical status using quantitative PCR for HPV E2 and E7 genes. Presence of intact E2 gene, as a surrogate marker for episomal HPV, was investigated with conventional PCR. Fifteen different HPV types were detected in HNSCC cases and HPV16 was present in 74% of the HPV-positive cases. HPV was detected in 65% (92/141) and 11% (15/134) of oropharyngeal and non-oropharyngeal carcinomas, respectively (P<0.0001). HPV was detected in 73% (75/103) of tonsillar carcinomas. The median load of HPV16 was 13 copies cell-1 (range 0.003–1080). Among HPV16-positive patients with oropharyngeal carcinoma, metastases to regional lymph nodes were observed in 100% (17/17) and 68% (40/58) for those with <1 HPV16 copy cell-1 and >1 HPV16 copy Cell-1, respectively (P=0.007). Among HPV16 cases, purely integrated HPV16 was found in 6%, whereas entirely episomal and mixed virus was detected in 51 and 42% of cases, respectively. Conclusively, HPV16 viral DNA load demonstrated a large diversity among HNSCCs. Although integration of HPV16 is common (48%), the episomal HPV16 is salient (93%) among HPV16 HNSCCs. In addition, low amount of HPV16 was associated with lymph node metastases among oropharyngeal carcinomas.
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| 18. |
- Faust, Helena, et al.
(författare)
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Pseudovirion-binding and neutralizing antibodies to cutaneous Human Papillomaviruses correlated to presence of HPV DNA in skin.
- 2013
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 94, s. 1096-1103
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Tidskriftsartikel (refereegranskat)abstract
- We compared seroreactivity to Human papillomavirus (HPV) antigens measured with two different high-throughput assays. One method used GST-L1 fusion proteins and the other heparin-bound HPV pseudovirions as antigens and both methods used multiplexed fluorescent beads for detection. For six HPV types (5, 6, 15, 16, 32 and 38), seroreactivity could be measured in parallel for 434 serum samples from non-immunosuppressed patients with skin lesions (squamous cell carcinoma of the skin, basal cell carcinoma of the skin, actinic keratosis and benign skin lesions). Biopsies from the skin lesions were tested for presence of HPV DNA using three different PCR methods, with typing by sequencing. Among the types included in the serological tests, HPV DNA of types HPV5, 15, 38 and 76 were most frequently detected in the tumours. Serum samples from subjects with HPV DNA positive biopsies and randomly selected serum samples from subjects with HPV DNA negative biopsies were also tested with neutralization assays with HPV5, 38 and 76 pseudovirions. Agreement of the three serological methods varied from poor to moderate and showed limited consistency. Type-specific seroprevalences among patients positive for the same type of HPV DNA (sensitivity of serology) was improved with the pseudovirion-based method (average of 40%, maximum 63%) compared to the GST-L1 method (average of 20%, maximum of 25%). Neutralization was the most sensitive assay for HPV38 (50%). In summary, the pseudovirion-based methods appeared to have an improved sensitivity.
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| 19. |
- Faust, Helena, et al.
(författare)
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Validation of multiplexed human papillomavirus serology using pseudovirions bound to heparin coated beads.
- 2010
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 91, s. 1840-1848
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Tidskriftsartikel (refereegranskat)abstract
- We developed and validated a high-throughput human papillomavirus (HPV) serology method based on Luminex technology, using pseudovirions (PsVs) of eight mucosal HPV types (HPV 6, 11, 16, 18, 31, 45, 52 and 58) and two cutaneous HPV types (HPV 5 and 38) bound to heparin coated beads. Analysis with neutralising type-specific monoclonal antibodies against included HPV types indicated type-specificity of the assay. Analysis of negative control serum samples from 63 children and 71 middle-aged women with up to one lifetime sexual partner indicated high specificity. Positive control serum samples from subjects with known HPV DNA status or clinical diagnosis found expected sensitivities for most of the HPV types in 219 European serum samples, but less than expected in 124 samples from Africa. HPV 45 and 52 did not react as expected with the human serum samples. The Pseudovirion-Luminex method was used to determine the HPV-seropositivity-associated relative risk for future cervical cancer using 208 serum samples from a prospective study of 18814 women followed for 23 years, previously analysed with standard HPV 16 ELISA. The Pseudovirion-Luminex method gave similar results as ELISA (Kappa= 0.77). As expected, HPV seropositivities assayed using the Pseudovirion-Luminex method found increased risk for cervical cancer for HPV 16 (OR=7.7, CI 95%=2.6-23) and HPV 31(OR=4.1, CI 95%=1.6-10.8), non-significant tendencies for increased risk for other mucosal HPV types and no risk for the cutaneous HPV types. In summary, multiplexed HPV serology using mammalian-derived pseudovirions selected for native conformation by binding to heparin-coated beads is validated as a high-throughput HPV serological method, for most of the analysed HPV types.
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| 20. |
- Fegraeus, K. Jaderkvist, et al.
(författare)
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Different DMRT3 Genotypes Are Best Adapted for Harness Racing and Riding in Finnhorses
- 2015
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Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 106:6, s. 734-740
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies showed a positive effect of the DMRT3 "gait keeper" mutation on harness racing performance in Standardbreds, French-, and Nordic trotters. The mutation has also been shown to influence riding traits in multiple breeds. This study investigated the effect of the DMRT3 mutation on harness racing performance and riding traits in Finnhorses. Finnhorses used for harness racing (n = 180) and for riding (n = 59) were genotyped for the DMRT3 mutation. For the trotters the genotypes were evaluated for association with racing performance (number of starts, victories, placings, earnings, and race times). At 3-6 years of age the AA genotype was superior compared with the CA and CC genotypes. The AA horses had a significantly higher proportion of victories (P = 1.4 x 10(-6)) and placings (P = 4.1 x 10(-7)), better race times (P = 0.01), and earned more money (P = 0.009) compared with C-horses. For the Finnhorses used for riding the owners answered a questionnaire to score how well the horse performed the gaits walk, trot, and canter on a scale from 1 to 6. These scores were tested for association with the DMRT3 genotypes. Although AA horses were more successful as racehorses, the CC and CA horses appear more adapted for classical riding disciplines. The AA horses received significantly lower gait scores compared with C-horses for the majority of gaits. Except for rhythm in extended canter (P = 0.05), there were no significant differences between CA and CC horses. This study shows that there are different optimal genotypes for different disciplines and the DMRT3 mutation clearly influences gaits and performance in Finnhorses.
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| 21. |
- Francois, Liesbeth, et al.
(författare)
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Conformation Traits and Gaits in the Icelandic Horse are Associated with Genetic Variants in Myostatin (MSTN)
- 2016
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Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 107:5, s. 431-437
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Tidskriftsartikel (refereegranskat)abstract
- Many genes are known to have an influence on conformation and performance traits; however, the role of one gene, Myostatin (MSTN), has been highlighted in recent studies on horses. Myostatin acts as a repressor in the development and regulation of differentiation and proliferative growth of skeletal muscle. Several studies have examined the link between MSTN, conformation, and performance in racing breeds, but no studies have investigated the relationship in Icelandic horses. Icelandic horses, a highly unique breed, are known both for their robust and compact conformation as well as their additional gaits tolt and pace. Three SNPs (g.65868604G>T [PR8604], g.66493737C>T [PR3737], and g.66495826A>G [PR5826]) flanking or within equine MSTN were genotyped in 195 Icelandic horses. The SNPs and haplotypes were analyzed for association with official estimated breeding values (EBV) for conformation traits (n = 11) and gaits (n = 5). The EBV for neck, withers, and shoulders was significantly associated with both PR8604 and PR3737 (P < 0.05). PR8604 was also associated with EBV for total conformation (P = 0.05). These associations were all supported by the haplotype analysis. However, while SNP PR5826 showed a significant association with EBVs for leg stance and hooves (P < 0.05), haplotype analyses for these traits failed to fully support these associations. This study demonstrates the possible role of MSTN on both the form and function of horses from non-racing breeds. Further analysis of Icelandic horses as well as other non-racing breeds would be beneficial and likely help to completely understand the influence of MSTN on conformation and performance in horses.
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| 22. |
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| 23. |
- Gavier-Widén, Dolores, et al.
(författare)
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Proposal for a unified classification system and nomenclature of lagoviruses
- 2017
-
Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 98, s. 1658-1666
-
Tidskriftsartikel (refereegranskat)abstract
- Lagoviruses belong to the Caliciviridae family. They were first recognized as highly pathogenic viruses of the European rabbit (Oryctolagus cuniculus) and European brown hare (Lepus europaeus) that emerged in the 1970-1980s, namely, rabbit haemorrhagic disease virus (RHDV) and European brown hare syndrome virus (EBHSV), according to the host species from which they had been first detected. However, the diversity of lagoviruses has recently expanded to include new related viruses with varying pathogenicity, geographic distribution and host ranges. Together with the frequent recombination observed amongst circulating viruses, there is a clear need to establish precise guidelines for classifying and naming lagovirus strains. Therefore, here we propose a new nomenclature based on phylogenetic relationships. In this new nomenclature, a single species of lagovirus would be recognized and called Lagovirus europaeus. The species would be divided into two genogroups that correspond to RHDV- and EBHSV-related viruses, respectively. Genogroups could be subdivided into genotypes, which could themselves be subdivided into phylogenetically well-supported variants. Based on available sequences, pairwise distance cutoffs have been defined, but with the accumulation of new sequences these cutoffs may need to be revised. We propose that an international working group could coordinate the nomenclature of lagoviruses and any proposals for revision.
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| 24. |
- Gonzalez, Elena G., et al.
(författare)
-
Phylogeography and Population Genetic Analyses in the Iberian Toothcarp (Aphanius iberus Valenciennes, 1846) at Different Time Scales
- 2018
-
Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 109:3, s. 253-263
-
Tidskriftsartikel (refereegranskat)abstract
- Secondary freshwater fish species inhabiting fluctuating and extreme environments are susceptible to changes in dispersion, effective population size, and genetic structure. The Iberian toothcarp Aphanius iberus is an endemic cyprinodontid of the Iberian Peninsula restricted to brackish water of salt marshes and coastal lagoons on the eastern Spanish Mediterranean coast. In this study, we analyzed mitochondrial cytochrome b (cyt b) DNA and microsatellite variation to evaluate ways in which the processes of extinction, dispersal, and colonization of A. iberus across its geographic distribution have affected its population genetic structure over time and space. The A. iberus network reconstruction indicated subtle levels of phylogeographic structuring.This, combined with substantial mitochondrial DNA (mtDNA) genetic diversity, suggests that Pleistocene glaciations had a lesser effect on the demographic structure of its populations than was the case for Iberian freshwater species with a similar distribution. Haplotype network, hierarchical analysis of molecular variance, and pairwise ΦST comparisons involving some Levantine samples showed a relatively high degree of mtDNA differentiation, which could be explained by historical isolation of the Villena Lagoon population. Conversely, significant genetic differentiation that follows an isolation-by-distance pattern, and a reduction in Ne though time was detected with microsatellites, suggesting extensive habitat fragmentation on the Mediterranean coast of the Iberian Peninsula over the past hundreds of years. At a smaller geographical scale (Mar Menor Lagoon), habitat fragmentation, probably due to human activity, appears to have resulted in substantially reduced migration and increased genetic drift, as shown by expanded genetic differentiation of populations.Subject areas: Population structure and phylogeography, Conservation
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| 25. |
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| 26. |
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| 27. |
- Gustafsson, RKL, et al.
(författare)
-
Direct infection of primary endothelial cells with human cytomegalovirus prevents angiogenesis and migration
- 2015
-
Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 96:12, s. 3598-3612
-
Tidskriftsartikel (refereegranskat)abstract
- Human cytomegalovirus (hCMV) is a beta herpesvirus that establishes lifelong infection. Although the virus does not usually cause overt clinical symptoms in immunocompetent individuals it can have deleterious effects in immunocompromised patients, such as those on post-transplant medication or with HIV infection. hCMV is the most common congenital infection and can lead to serious fetal sequelae. Endothelial cells (ECs) are natural hosts for hCMVin vivo, therefore, investigations of how this cell type is modulated by infection are key to understanding hCMV pathogenesis. Previous studies have examined the effect of secretomes from hCMV-infected cells on EC angiogenesis, whereas the effect of direct infection on this process has not been so well investigated. Here, we show that placental ECs are viral targets during congenital infection and that vessels in infected tissue appear morphologically abnormal. We demonstrate that the clinical hCMV strain VR1814 impaired EC tube assembly inin vitroangiogenesis assays and inhibited wound healing ability in scratch assays. Secretomes from infected cultures did not impair angiogenesis of uninfected ECs, suggesting that cell-intrinsic changes, as opposed to secreted factors, were responsible. We observed viral gene transcription dependent downregulation of the expression of angiogenesis-associated genes, including angiopoietin-2, TEK receptor and vascular endothelial growth factor receptors. An alternative clinical hCMV stain, TB40E showed similar effects on EC angiogenesis. Together, our data indicate that direct infection with hCMV can induce an anti-migratory and anti-angiogenic EC phenotype, which could have a detrimental effect on the vasculature development in infected tissues.
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| 28. |
- Hedrick, Philip W., et al.
(författare)
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Genomic Variation of Inbreeding and Ancestry in the Remaining Two Isle Royale Wolves
- 2017
-
Ingår i: Journal of Heredity. - : OXFORD UNIV PRESS INC. - 0022-1503 .- 1465-7333. ; 108:2, s. 120-126
-
Tidskriftsartikel (refereegranskat)abstract
- Inbreeding, relatedness, and ancestry have traditionally been estimated with pedigree information, however, molecular genomic data can provide more detailed examination of these properties. For example, pedigree information provides estimation of the expected value of these measures but molecular genomic data can estimate the realized values of these measures in individuals. Here, we generate the theoretical distribution of inbreeding, relatedness, and ancestry for the individuals in the pedigree of the Isle Royale wolves, the first examination of such variation in a wild population with a known pedigree. We use the 38 autosomes of the dog genome and their estimated map lengths in our genomic analysis. Although it is known that the remaining wolves are highly inbred, closely related, and descend from only 3 ancestors, our analyses suggest that there is significant variation in the realized inbreeding and relatedness around pedigree expectations. For example, the expected inbreeding in a hypothetical offspring from the 2 remaining wolves is 0.438 but the realized 95% genomic confidence interval is from 0.311 to 0.565. For individual chromosomes, a substantial proportion of the whole chromosomes are completely identical by descent. This examination provides a background to use when analyzing molecular genomic data for individual levels of inbreeding, relatedness, and ancestry. The level of variation in these measures is a function of the time to the common ancestor(s), the number of chromosomes, and the rate of recombination. In the Isle Royale wolf population, the few generations to a common ancestor results in the high variance in genomic inbreeding.
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| 29. |
- Hepojoki, J, et al.
(författare)
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Acute hantavirus infection induces galectin-3-binding protein
- 2014
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 95:Pt 11, s. 2356-2364
-
Tidskriftsartikel (refereegranskat)abstract
- Hantaviruses are zoonotic viruses that cause life-threatening diseases when transmitted to humans. Severe hantavirus infection is manifested by impairment of renal function, pulmonary oedema and capillary leakage. Both innate and adaptive immune responses contribute to the pathogenesis, but the underlying mechanisms are not fully understood. Here, we showed that galectin-3-binding protein (Gal-3BP) was upregulated as a result of hantavirus infection bothin vitroandin vivo. Gal-3BP is a secreted glycoprotein found in human serum, and increased Gal-3BP levels have been reported in chronic viral infections and in several types of cancer. Ourin vitroexperiments showed that, whilst Vero E6 cells (an African green monkey kidney cell line) constitutively expressed and secreted Gal-3BP, this protein was detected in primary human cells only as a result of hantavirus infection. Analysis of Gal-3BP levels in serum samples of cynomolgus macaques infected experimentally with hantavirus indicated that hantavirus infection induced Gal-3BP alsoin vivo. Finally, analysis of plasma samples collected from patients hospitalized because of acute hantavirus infection showed higher Gal-3BP levels during the acute than the convalescent phase. Furthermore, the Gal-3BP levels in patients with haemorrhagic fever with renal syndrome correlated with increased complement activation and with clinical variables reflecting the severity of acute hantavirus infection.
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| 30. |
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| 31. |
- Häggström, Jens, et al.
(författare)
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Identification of 2 Loci Associated with Development of Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniels
- 2011
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Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 102, s. S62-S67
-
Tidskriftsartikel (refereegranskat)abstract
- Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs. It is characterized by chronic progressive degenerative lesions of the mitral valve. The valve leaflets become thickened and prolapse into the left atrium resulting in mitral regurgitation (MR). MMVD is most prevalent in small to medium sized dog breeds, Cavalier King Charles Spaniels (CKCS) in particular. The onset of MMVD is highly age dependent, and at the age of 10 years, nearly all CKCS are affected. The incidence of a similar disease in humans-mitral valve prolapse-is 1-5%. By defining CKCSs with an early onset of MMVD as cases and old dogs with no or mild signs of MMVD as controls, we conducted a genome-wide association study (GWAS) to identify loci associated with development of MMVD. We have identified a 1.58 Mb region on CFA13 (P(genome) = 4.0x 10(-5)) and a 1.68 Mb region on CFA14 (P(genome) = 7.9x 10(-4)) associated with development of MMVD. This confirms the power of using the dog as a model to uncover potential candidate regions involved in the molecular mechanisms behind complex traits.
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| 32. |
- Iheozor-Ejiofor, Rommel Paneth, et al.
(författare)
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Vaccinia virus-free rescue of fluorescent replication-defective vesicular stomatitis virus and pseudotyping with Puumala virus glycoproteins for use in neutralization tests
- 2016
-
Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 97, s. 1052-1059
-
Tidskriftsartikel (refereegranskat)abstract
- Puumala virus (PUUV) grows slowly in cell culture. To study antigenic properties of PUUV, an amenable method for their expression would be beneficial. To achieve this, a replication-defective recombinant vesicular stomatitis virus, rVSV Delta G*EGFP, was rescued using BSRT7/5 and encephalomyocarditis virus (EMCV) internal ribosomal entry site (IRES)-enabled rescue plasmids. Using these particles, pseudotypes bearing PUUV Sotkamo strain glycoproteins were produced, with titres in the range 10(5)-10(8), and were used in pseudotype focus reduction neutralization tests (pFRNTs) with neutralizing monoclonal antibodies and patient sera. The results were compared with those from orthodox focus reduction neutralization tests (oFRNTs) using native PUUV with the same samples and showed a strong positive correlation (r(s)=0.82) between the methods. While developing the system we identified three amino acids which were mutated in the Vero E6 cell culture adapted PUUV prototype Sotkamo strain sequence, and changing these residues was critical for expression and neutralizing antibody binding of PUUV glycoproteins.
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| 33. |
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| 34. |
- Johansson Wensman, Jonas, et al.
(författare)
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The X proteins of bornaviruses interfere with type I interferon signalling
- 2013
-
Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 94, s. 263-269
-
Tidskriftsartikel (refereegranskat)abstract
- Borna disease virus (BDV) is a neurotropic, negative-stranded RNA virus causing persistent infection and progressive neurological disorders in a wide range of warm-blooded animals. The role of the small non-structural X protein in viral pathogenesis is not completely understood. Here we investigated whether the X protein of BDV and avian bornavirus (ABV) interferes with the type I interferon (IFN) system, similar to other non-structural proteins of negative-stranded RNA viruses. In luciferase reporter assays, we found that the X protein of various bornaviruses interfered with the type I IFN system at all checkpoints investigated, in contrast to previously reported findings, resulting in reduced type I IFN secretion.
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| 35. |
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| 36. |
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| 37. |
- Leijon, Mikael, et al.
(författare)
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Genetic variation and Dynamics of infections of equine herpesvirus type 5 in individual horses
- 2016
-
Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 97, s. 169-178
-
Tidskriftsartikel (refereegranskat)abstract
- Equid herpesvirus 5 (EHV-5) is related to the human Epstein-Barr virus (human herpesvirus 4) and has frequently been observed in equine populations worldwide. EHV-5 was previously assumed to be low to non-pathogenic; however, studies have also related the virus to the severe lung disease equine multinodular pulmonary fibrosis (EMPF). Genetic information of EHV-5 is scanty: the whole genome was recently described and only limited nucleotide sequences are available. In this study, samples were taken twice 1 year apart from eight healthy horses at the same professional training yard and samples from a ninth horse that was diagnosed with EMPF with samples taken pre- and post-mortem to analyse partial glycoprotein B (gB) gene of EHV-5 by using next-generation sequencing. The analysis resulted in 27 partial gB gene sequences, 11 unique sequence types and five amino acid sequences. These sequences could be classified within four genotypes (I-IV) of the EHV-5 gB gene based on the degree of similarity of the nucleotide and amino acid sequences, and in this work horses were shown to be identified with up to three different genotypes simultaneously. The observations showed a range of interactions between EHV-5 and the host over time, where the same virus persists in some horses, whereas others have a more dynamic infection pattern including strains from different genotypes. This study provides insight into the genetic variation and dynamics of EHV-5, and highlights that further work is needed to understand the EHV-5 interaction with its host.
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| 38. |
- Levanov, Lev, et al.
(författare)
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Defining of MAbs-neutralizing sites on the surface glycoproteins Gn and Gc of a hantavirus using vesicular stomatitis virus pseudotypes and site-directed mutagenesis
- 2019
-
Ingår i: Journal of General Virology. - : MICROBIOLOGY SOC. - 0022-1317 .- 1465-2099. ; 100:2, s. 145-155
-
Tidskriftsartikel (refereegranskat)abstract
- Earlier four monoclonal antibodies (MAbs) against surface glycoproteins Gn and Gc of puumala virus (PUUV, genus Orthohantavirus, family Hantaviridae, order Bunyavirales) were generated and for three MAbs with neutralizing capacity the localization of binding epitopes was predicted using pepscan and phage-display techniques. In this work, we produced vesicular stomatitis virus (VSV) particles pseudotyped with the Gn and Gc glycoproteins of PUUV and applied site-directed mutagenesis to dissect the structure of neutralizing epitopes. Replacement of cysteine amino acid (aa) residues with alanines resulted in pseudotype particles with diminished (16 to 18 %) neut-titres; double Cys -> Ala mutants, as well as mutants with bulky aromatic and charged residues replaced with alanines, have shown even stronger reduction in neut-titres (from 25 % to the escape phenotype). In silico modelling of the neut-epitopes supported the hypothesis that these critical residues are located on the surface of viral glycoprotein molecules and thus can be recognized by the antibodies indeed. A similar pattern was observed in experiments with mutant pseudotypes and sera collected from patients suggesting that these neut-epitopes are utilized in a course of human PUUV infection. These data will help understanding the mechanisms of hantavirus neutralization and assist construction of vaccine candidates.
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| 39. |
- Lewis, Nicola S., et al.
(författare)
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Influenza A virus evolution and spatio-temporal dynamics in Eurasian wild birds : a phylogenetic and phylogeographical study of whole-genome sequence data
- 2015
-
Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 96, s. 2050-2060
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Tidskriftsartikel (refereegranskat)abstract
- Low pathogenic avian influenza A viruses (IAVs) have a natural host reservoir in wild waterbirds and the potential to spread to other host species. Here, we investigated the evolutionary, spatial and temporal dynamics of avian IAVs in Eurasian wild birds. We used whole-genome sequences collected as part of an intensive long-term Eurasian wild bird surveillance study, and combined this genetic data with temporal and spatial information to explore the virus evolutionary dynamics. Frequent reassortment and co-circulating lineages were observed for all eight genomic RNA segments over time. There was no apparent species-specific effect on the diversity of the avian IAVs. There was a spatial and temporal relationship between the Eurasian sequences and significant viral migration of avian lAVs from West Eurasia towards Central Eurasia. The observed viral migration patterns differed between segments. Furthermore, we discuss the challenges faced when analysing these surveillance and sequence data, and the caveats to be borne in mind when drawing conclusions from the apparent results of such analyses.
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| 40. |
- Lidqvist, Maria, et al.
(författare)
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Detection of human papillomavirus oncoprotein E7 in liquid-based cytology
- 2012
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 93:2, s. 356-363
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Tidskriftsartikel (refereegranskat)abstract
- The selection and characterization of a set of mouse mAbs against high-risk human papillomavirus (HPV) E7 oncoprotein and the development of protocols for immunocytochemistry (ICC) are described here. A large number of antibodies raised towards HPV16 and 18 E7 were tested for high-risk specificity by ELISA using a panel of HPV E7 proteins. Antibodies detecting low-risk E7 were discarded, resulting in 38 high-risk HPV E7-specific antibodies. The corresponding epitopes were mapped using overlapping HPV E7 fragments displayed on phage particles. Functionality in ICC against formalin-fixed cervical cancer cell lines was demonstrated for ten mAbs; their high-risk specificity was confirmed by Western blot analysis and ICC on transiently transformed cells expressing high- or low-risk HPV E7. These mAbs were specific for one or several of the high-risk strains HPV16, 18, 31, 35 and 45. Specific E7 staining of liquid-based cytology (LBC) samples was demonstrated for seven mAbs and optimized protocols were established. The E716-41 and E718-79 mAbs demonstrated particularly strong and specific staining of cells stored in LBC fluid for at least 6 months. It is proposed that the high-risk HPV E7 staining protocols established in this study may have the potential to be included in a complementary test for the detection and identification of malignantly transformed cells, in for example atypical squamous cells of undetermined significance samples.
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| 41. |
- Lin, J., et al.
(författare)
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Novel hepatitis E like virus found in Swedish moose
- 2014
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 95:PART3, s. 557-570
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Tidskriftsartikel (refereegranskat)abstract
- A novel virus was detected in a sample collected from a Swedish moose (Alces alces). The virus was suggested as a member of the Hepeviridae family, although it was found to be highly divergent from the known four genotypes (gt1-4) of hepatitis E virus (HEV). Moose are regularly hunted for consumption in the whole of Scandinavia. Thus, the finding of this virus may be important from several aspects: (a) as a new diverged HEV in a new animal species, and (b) potential unexplored HEV transmission pathways for human infections. Considering these aspects, we have started the molecular characterization of this virus. A 5.1 kb amplicon was sequenced, and corresponded to the partial ORF1, followed by complete ORF2, ORF3 and poly(A) sequence. In comparison with existing HEVs, the moose HEV genome showed a general nucleotide sequence similarity of 37-63% and an extensively divergent putative ORF3 sequence. The junction region between the ORFs was also highly divergent; however, two putative secondary stem-loop structures were retained when compared to gt1-4, but with altered structural appearance. In the phylogenetic analysis, the moose HEV deviated and formed its own branch between the gt1-4 and other divergent animal HEVs. The characterization of this highly divergent genome provides important information regarding the diversity of HEV infecting various mammalian species. However, further studies are needed to investigate its prevalence in the moose populations and possibly in other host species, including the risk for human infection. © 2014 Statens Veterinarmedicinska Anstalt.
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| 42. |
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| 43. |
- Lionikas, Arimantas, et al.
(författare)
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Genomic Analysis of Variation in Hindlimb Musculature of Mice from the C57BL/6J and DBA/2J Lineage
- 2010
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Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 101:3, s. 360-367
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Tidskriftsartikel (refereegranskat)abstract
- The precise locations of attachment points of muscle to bone-the origin and insertion sites-are crucial anatomical and functional characteristics that influence locomotor performance. Mechanisms that control the development of these interactions between muscle, tendon, and bone are currently not well understood. In a subset of BXD recombinant inbred (RI) strains derived from the C57BL/6J and DBA/2J strains, we observed a soleus femoral attachment anomaly (SFAA) that was rare in both parental strains (Lionikas, Glover et al. 2006). The aim of the present study was to assess suitability of SFAA as a model to study the genetic mechanisms underlying variation in musculoskeletal anatomy. We scored the incidence of SFAA in 55 BXD strains (n = 9 to 136, median = 26, phenotyped animals per strain, for a total number of 2367). Seven strains (BXD1, 12, 38, 43, 48, 54, and 56) exhibited a high incidence of unilateral SFAA (47-89%), whereas 23 strains scored 0%. Exploration of the mechanisms underlying SFAA in 2 high incidence strains, BXD1 and BXD38, indicated that SFAA-relevant genes are to be found in both C57BL/6J and DBA/2J regions of the BXD1 genome. However, not all alleles relevant for the expression of the phenotype were shared between the 2 high-incidence BXD strains. In conclusion, the anatomical origin of the soleus muscle in mouse is controlled by a polygenic system. A panel of BXD RI strains is a useful tool in exploring the genetic mechanisms underlying SFAA and improving our understanding of musculoskeletal development.
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| 44. |
- Liu, LF, et al.
(författare)
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RNA processing bodies are disassembled during Old World alphavirus infection
- 2019
-
Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 100:10, s. 1375-1389
-
Tidskriftsartikel (refereegranskat)abstract
- RNA processing bodies (P-bodies) are non-membranous cytoplasmic aggregates of mRNA and proteins involved in mRNA decay and translation repression. P-bodies actively respond to environmental stresses, associated with another type of RNA granules, known as stress granules (SGs). Alphaviruses were previously shown to block SG induction at late stages of infection, which is important for efficient viral growth. In this study, we found that P-bodies were disassembled or reduced in number very early in infection with Semliki Forest virus (SFV) or chikungunya virus (CHIKV) in a panel of cell lines. Similar to SGs, reinduction of P-bodies by a second stress (sodium arsenite) was also blocked in infected cells. The disassembly of P-bodies still occurred in non-phosphorylatable eIF2α mouse embryonal fibroblasts (MEFs) that are impaired in SG assembly. Studies of translation status by ribopuromycylation showed that P-body disassembly is independent of host translation shutoff, which requires the phosphorylation of eIF2α in the SFV- or CHIKV-infected cells. Labelling of newly synthesized RNA with bromo-UTP showed that host transcription shutoff correlated with P-body disassembly at the same early stage (3–4 h) after infection. However, inhibition of global transcription with actinomycin D (ActD) failed to disassemble P-bodies as effectively as the viruses did. Interestingly, blocking nuclear import with importazole led to an efficient P-bodies loss. Our data reveal that P-bodies are disassembled independently from SG formation at early stages of Old World alphavirus infection and that nuclear import is involved in the dynamic of P-bodies.
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| 45. |
- Lukhovitskaya, Nina, et al.
(författare)
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A viral transcription factor exhibits antiviral RNA silencing suppression activity independent of its nuclear localization
- 2014
-
Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 95, s. 2831-2837
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Tidskriftsartikel (refereegranskat)abstract
- Viral suppressors of RNA silencing (VSRs) are critical for the success of virus infection and efficient accumulation of virus progeny. The chrysanthemum virus B p12 protein acts as a transcription factor to regulate cell size and proliferation favourable for virus infection. Here, we showed that the p12 protein suppressed RNA silencing and was able to complement a VSR-deficient unrelated virus. Moreover, p12 counter-silencing activity could be uncoupled from its function as a transcription factor in the nucleus. The altered p12 protein, which lacked a nuclear localization signal and was not imported into the nucleus, was able to suppress RNA silencing as efficiently as the native protein. The data revealed new aspects of p12 functioning and identified a novel role for this viral zinc-finger transcription factor. The results provided a general insight into one of the activities of the p12 protein, which appeared to possess more than one function.
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| 46. |
- Lukhovitskaya, Nina
(författare)
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Dynamic localization of two tobamovirus ORF6 proteins involves distinct organellar compartments
- 2013
-
Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 94, s. 230-240
-
Tidskriftsartikel (refereegranskat)abstract
- ORF6 is a small gene that overlaps the movement and coat protein genes of subgroup la tobamoviruses. The ORF6 protein of tomato mosaic virus (ToMV) strain L (L-ORF6), interacts in vitro with eukaryotic elongation factor la, and mutation of the ORF6 gene of tobacco mosaic virus (TMV) strain U1 (U1-ORF6) reduces the pathogenicity in vivo of TMV, whereas expression of this gene from two other viruses, tobacco rattle virus (TRV) and potato virus X (PVX), increases their pathogenicity. In this work, the in vivo properties of the L-ORF6 and U1-ORF6 proteins were compared to identify sequences that direct the proteins to different subcellular locations and also influence virus pathogenicity. Site-specific mutations in the ORF6 protein were made, hybrid ORF6 proteins were created in which the N-terminal and C-terminal parts were derived from the two proteins, and different subregions of the protein were examined, using expression either from a recombinant TRV vector or as a yellow fluorescent protein fusion from a binary plasmid in Agrobacterium tumefaciens. L-ORF6 caused mild necrotic symptoms in Nicotiana benthamiana when expressed from TRV, whereas U1-ORF6 caused severe symptoms including death of the plant apex. The difference in symptoms was associated with the C-terminal region of L-ORF6, which directed the protein to the endoplasmic reticulum (ER), whereas U1-ORF6 was directed initially to the nucleolus and later to the mitochondria. Positively charged residues at the N terminus allowed nucleolar entry of both U1-ORF6 and L-ORF6, but hydrophobic residues at the C terminus of L-ORF6 directed this protein to the ER.
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| 47. |
- Magnius, L., et al.
(författare)
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ICTV Virus Taxonomy Profile: Deltavirus
- 2018
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 99:12, s. 1565-1566
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis delta virus, the only member of the only species in the genus Deltavirus, is a unique human pathogen. Its -1.7 kb circular negative-sense RNA genome encodes a protein, hepatitis delta antigen, which occurs in two forms, small and large, both with unique functions. Hepatitis delta virus uses host RNA polymerase II to replicate via double rolling circle RNA synthesis. Newly synthesized linear RNAs are circularized after autocatalytic cleavage and ligation. Hepatitis delta virus requires the envelope of the helper virus, hepatitis B virus (family Hepadnaviridae), to produce infectious particles. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of Deltavirus which is available at www.ictv.global/report/deltavirus.
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| 48. |
- Matsubara, K., et al.
(författare)
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No Interstitial Telomeres on Autosomes but Remarkable Amplification of Telomeric Repeats on the W Sex Chromosome in the Sand Lizard (Lacerta agilis)
- 2015
-
Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 106:6, s. 753-757
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Tidskriftsartikel (refereegranskat)abstract
- Telomeres are repeat ( TTAGGG) (n) sequences that form terminal ends of chromosomes and have several functions, such as protecting the coding DNA from erosion at mitosis. Due to chromosomal rearrangements through evolutionary history ( e.g., inversions and fusions), telomeric sequences are also found between the centromere and the terminal ends ( i.e., at interstitial telomeric sites, ITSs). ITS telomere sequences have been implicated in heritable disease caused by genomic instability of ITS polymorphic variants, both with respect to copy number and sequence. In the sand lizard ( Lacerta agilis), we have shown that telomere length is predictive of lifetime fitness in females but not males. To assess whether this sex specific fitness effect could be traced to ITSs differences, we mapped ( TTAGGG) n sequences using fluorescence in situ hybridization in fibroblast cells cultured from 4 specimens of known sex. No ITSs could be found on autosomes in either sex. However, females have heterogametic sex chromosomes in sand lizards ( ZW, 2n = 38) and the female W chromosome showed degeneration and remarkable ( TTAGGG) n amplification, which was absent in the Z chromosomes. This work warrants further research on sex chromosome content, in particular of the degenerate W chromosome, and links to female fitness in sand lizards.
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- Moens, U, et al.
(författare)
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ICTV Virus Taxonomy Profile: Polyomaviridae
- 2017
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 98:6, s. 1159-1160
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Tidskriftsartikel (refereegranskat)
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