| 1. |
- Adams, Jimi, et al.
(författare)
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Peer Network Processes in Adolescents' Health Lifestyles
- 2022
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Ingår i: Journal of health and social behavior. - : SAGE Publications. - 0022-1465 .- 2150-6000. ; 63:1, s. 125-141
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Tidskriftsartikel (refereegranskat)abstract
- Combining theories of health lifestyles-interrelated health behaviors arising from group-based identities-with those of network and behavior change, we investigated network characteristics of health lifestyles and the role of influence and selection processes underlying these characteristics. We examined these questions in two high schools using longitudinal, complete friendship network data from the National Longitudinal Study of Adolescent to Adult Health. Latent class analyses characterized each school's predominant health lifestyles using several health behavior domains. School-specific stochastic actor-based models evaluated the bidirectional relationship between friendship networks and health lifestyles. Predominant lifestyles remained stable within schools over time, even as individuals transitioned between lifestyles. Friends displayed greater similarity in health lifestyles than nonfriend dyads. Similarities resulted primarily from teens' selection of friends with similar lifestyles but also from teens influencing their peers' lifestyles. This study demonstrates the salience of health lifestyles for adolescent development and friendship networks.
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| 2. |
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| 3. |
- 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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| 4. |
- Abdel-Hamid, Mohamed, et al.
(författare)
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Genetic diversity in hepatitis C virus in Egypt and possible association with hepatocellular carcinoma
- 2007
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 88:5, s. 1526-1531
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Tidskriftsartikel (refereegranskat)abstract
- Egypt has one of the world's highest prevalences of hepatitis C virus (HCV) infection, with a majority of genotype 4 infections. To explore the genetic diversity of HCV in Egypt, sera from 131 Egyptians [56 from community studies, 37 chronic hepatitis patients, 28 hepatocellular carcinoma (HCC) patients and 10 patients with non-Hodgkin's lymphoma] were genotyped by restriction fragment-length polymorphism and phylogenetic analyses of sequences from the mid-core and non-structural 5B regions. The different genotyping methods showed good agreement. The majority of the viruses (83 of 131; 63 %) were of subtype 4a, but five other subtypes within genotype 4 were also observed, as well as three genotype 1b, five genotype 1g and one genotype 3a samples. Interestingly, subtype 4o, which was easily identifiable in all three genomic regions, 3 showed an association with HCC (P=0.017), which merits further investigation.
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| 5. |
- Abdurahman, S, et al.
(författare)
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Selected amino acid substitutions in the C-terminal region of human immunodeficiency virus type 1 capsid protein affect virus assembly and release
- 2004
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 85:Pt 10, s. 2903-2913
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Tidskriftsartikel (refereegranskat)abstract
- The capsid protein (CA or p24) of human immunodeficiency virus type 1 (HIV-1) plays a major role both early and late in the virus replication cycle. Many studies have suggested that the C-terminal domain of this protein is involved in dimerization and proper assembly of the viral core. Point mutations were introduced in two conserved sites of this region and their effects on viral protein expression, particle assembly and infectivity were studied. Eight different mutants (L205A+P207A, L205A, P207A, 223GPG225AAA, G223A, P224A, G225A and V221G) of the infectious clone pNL4-3 were constructed. Most substitutions had no substantial effect on HIV-1 protein synthesis, yet they impaired viral infectivity and particle production. The two mutants P207A and V221G also had a profound effect on Gag–Pol protein processing in HeLa–tat cells. However, these results were cell line-specific and Gag–Pol processing of P207A was not affected in 293T cells. In HeLa–tat cells, no virus particles were detected with the P207A mutation, whereas the other mutant virus particles were heterogeneous in size and morphology. None of the mutants showed normal, mature, conical core structures in HeLa–tat cells. These results indicate that the two conserved sequences in the C-terminal CA domain are essential for proper morphogenesis and infectivity of HIV-1 particles.
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| 6. |
- Adams, WC, et al.
(författare)
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Adenovirus serotype 5 infects human dendritic cells via a coxsackievirus-adenovirus receptor-independent receptor pathway mediated by lactoferrin and DC-SIGN
- 2009
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 90:Pt 7, s. 1600-1610
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Tidskriftsartikel (refereegranskat)abstract
- The coxsackievirus–adenovirus receptor (CAR) is the described primary receptor for adenovirus serotype 5 (Ad5), a common human pathogen that has been exploited as a viral vector for gene therapy and vaccination. This study showed that monocytes and dendritic cells (DCs), such as freshly isolated human blood myeloid DCs, plasmacytoid DCs and monocyte-derived DCs, are susceptible to recombinant Ad5 (rAd5) infection despite their lack of CAR expression. Langerhans cells and dermal DCs from skin expressed CAR, but blocking CAR only partly decreased rAd5 infection, together suggesting that other receptor pathways mediate viral entry of these cells. Lactoferrin (Lf), an abundant protein in many bodily fluids known for its antiviral and antibacterial properties, promoted rAd5 infection in all cell populations except plasmacytoid DCs using a CAR-independent process. Lf caused phenotypic differentiation of the DCs, but cell activation played only a minor role in the increase in infection frequencies. The C-type lectin receptor DC-SIGN facilitated viral entry of rAd5–Lf complexes and this was dependent on high-mannose-type N-linked glycans on Lf. These results suggest that Lf present at high levels at mucosal sites can facilitate rAd5 attachment and enhance infection of DCs. A better understanding of the tropism and receptor mechanisms of Ad5 may help explain Ad5 pathogenesis and guide the engineering of improved rAd vectors.
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| 7. |
- 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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| 8. |
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| 9. |
- Allander, T, et al.
(författare)
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Recombinant human monoclonal antibodies against different conformational epitopes of the E2 envelope glycoprotein of hepatitis C virus that inhibit its interaction with CD81
- 2000
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 81:10, s. 2451-2459
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Tidskriftsartikel (refereegranskat)abstract
- The antibody response to the envelope proteins of hepatitis C virus (HCV) may play an important role in controlling the infection. To allow molecular analyses of protective antibodies, we isolated human monoclonal antibodies to the E2 envelope glycoprotein of HCV from a combinatorial Fab library established from bone marrow of a chronically HCV-infected patient. Anti-E2 reactive clones were selected using recombinant E2 protein. The bone marrow donor carried HCV genotype 2b, and E2 used for selection was of genotype 1a. The antibody clones were expressed as Fab fragments in E. coli, and as Fab fragments and IgG1 in CHO cells. Seven different antibody clones were characterized, and shown to have high affinity for E2, genotype 1a. Three clones also had high affinity for E2 of genotype 1b. They all bind to conformation-dependent epitopes. Five clones compete for the same or overlapping binding sites, while two bind to one or two other epitopes of E2. Four clones corresponding to the different epitopes were tested as purified IgG1 for blocking the CD81-E2 interaction in vitro; all four were positive at 0.3-0.5 microg/ml. Thus, the present results suggest the existence of at least two conserved epitopes in E2 that mediate inhibition of the E2-CD81 interaction, of which one appeared immunodominant in this donor.
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| 10. |
- Almqvist, J, et al.
(författare)
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Functional interaction of Oct transcription factors with the family of repeats in Epstein-Barr virus oriP.
- 2005
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 86:Pt 5, s. 1261-7
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Tidskriftsartikel (refereegranskat)abstract
- The family of repeats (FR) is a major upstream enhancer of the Epstein-Barr virus (EBV) latent C promoter (Cp) that controls transcription of six different latent nuclear proteins following interaction with the EBV nuclear protein EBNA1. Here, it was shown that Cp could also be activated by octamer-binding factor (Oct) proteins. Physical binding to the FR by the cellular transcription factors Oct-1 and Oct-2 was demonstrated by using an electrophoretic mobility-shift assay. Furthermore, Oct-1 in combination with co-regulator Bob.1, or Oct-2 alone, could drive transcription of a heterologous thymidine kinase promoter linked to the FR in both B cells and epithelial cells. Cp controlled by the FR was also activated by binding of Oct-2 to the FR. This may have direct implications for B cell-specific regulation of Cp.
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| 11. |
- 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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| 12. |
- 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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| 13. |
- Andersson, Stefan, et al.
(författare)
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The genetic basis of naturally occurring pollen color dimorphisms in Nigella degenii (Ranunculaceae)
- 2005
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Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 96:5, s. 550-556
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Tidskriftsartikel (refereegranskat)abstract
- Nigella degenii ssp. barbro and ssp. jenny differ from related taxa in being dimorphic for pollen color, with some plants having dark pollen and others light pollen. In this study we performed experimental crosses to determine whether the difference in pollen color is governed by few or many loci and whether the two subspecies utilize the same gene to control pollen color. Patterns of segregation in crosses between morphs show that dark pollen is dominant over light pollen and that a single major gene is responsible for most of the variation in pollen color. Consequently it should be relatively easy for pollen color dimorphisms to establish and spread in these subspecies. Aberrant segregation ratios were attributed to genetic factors that reduced the expression of the allele conferring dark pollen or processes that sorted between color morphs during seed development. Crosses between dark pollen plants from different subspecies showed signs of complementation in the F-2 generation, but the frequency of the light morph was too low to support a model involving complementary action of recessive alleles at two separate loci. Based on this and other observations, we hypothesize that the pollen color difference is controlled by the same major locus in the two subspecies.
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| 14. |
- Antonsson, Annika, et al.
(författare)
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Prevalence and type spectrum of human papillomaviruses in healthy skin samples collected in three continents.
- 2003
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 84:Pt 7, s. 1881-1886
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Tidskriftsartikel (refereegranskat)abstract
- In order to investigate whether previous findings of ubiquitous skin papillomavirus infection in Caucasians apply to populations from other parts of the world, skin swab samples from Bangladesh, Japan, Ethiopia and Zambia were analysed in parallel with Swedish samples. The prevalence of HPV DNA in the material from Bangladesh was 68 %, Japan 54 %, Ethiopia 52 %, Zambia 42 % and Sweden 70 %. A great multiplicity of genotypes was demonstrated by the finding of 88 HPV types or putative types in 142 HPV DNA-positive samples in total. Double or multiple genotypes were frequently found in the same sample. The most prevalent HPV type was HPV-5, with an overall prevalence of 6·5 %. This was also the only type that was found in samples from all of the countries in the study. The results presented show that commensal skin HPV infections have a worldwide distribution with a very broad spectrum of genotypes.
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| 15. |
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| 16. |
- 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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| 17. |
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| 18. |
- Ayhan, Nazli, et al.
(författare)
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Field surveys in Croatia and North Macedonia reveal two novel phleboviruses circulating in sandflies
- 2021
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 102:11
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Tidskriftsartikel (refereegranskat)abstract
- Sandfly-borne phleboviruses are distributed widely throughout the Mediterranean Basin, presenting a threat to public health in areas where they circulate. However, the true diversity and distribution of pathogenic and apathogenic sandfly-borne phleboviruses remains a key issue to be studied. In the Balkans, most published data rely on serology-based studies although virus isolation has occasionally been reported. Here, we report the discovery of two novel sandfly-borne phleboviruses, provisionally named Zaba virus (ZABAV) and Bregalaka virus (BREV), which were isolated in Croatia and North Macedonia, respectively. This constitutes the first isolation of phleboviruses in both countries. Genetic analysis based on complete coding sequences indicated that ZABAV and BREV are distinct from each other and belong to the genus Phlebovirus, family Phenuiviridae. Phylogenetic and amino acid modelling of viral polymerase shows that ZABAV and BREV are new members of the Salehabad phlebovirus species and the Adana phlebovirus species, respectively. Moreover, sequence-based vector identification suggests that ZABAV is mainly transmitted by Phlebotomus neglectus and BREV is mainly transmitted by Phlebotomus perfiliewi. BREV neutralizing antibodies were detected in 3.3% of human sera with rates up to 16.7% in certain districts, demonstrating that BREV frequently infects humans in North Macedonia. In vitro viral growth kinetics experiments demonstrated viral replication of both viruses in mammalian and mosquito cells. In vivo experimental studies in mice suggest that ZABAV and BREV exhibit characteristics making them possible human pathogens.
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| 19. |
- 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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| 20. |
- Banabazi, Mohammad Hossein
(författare)
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Weighted Single-Step GWAS for Body Mass Index and Scans for Recent Signatures of Selection in Yorkshire Pigs
- 2022
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Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 113, s. 325-335
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Tidskriftsartikel (refereegranskat)abstract
- Controlling extra fat deposition is economically favorable in modern swine industry. Understanding the genetic architecture of fat deposition traits such as body mass index (BMI) can help in improving genomic selection for such traits. We utilized a weighted single-step genome-wide association study (WssGWAS) to detect genetic regions and candidate genes associated with BMI in a Yorkshire pig population. Three extended haplotype homozygosity (EHH)-related statistics were also incorporated within a de-correlated composite of multiple signals (DCMS) framework to detect recent selection signatures signals. Overall, the full pedigree consisted of 7016 pigs, of which 5561 had BMI records and 598 pigs were genotyped with an 80 K single nucleotide polymorphism (SNP) array. Results showed that the most significant windows (top 15) explained 9.35% of BMI genetic variance. Several genes were detected in regions previously associated with pig fat deposition traits and treated as potential candidate genes for BMI in Yorkshire pigs: FTMT, SRFBP1, KHDRBS3, FOXG1, SOD3, LRRC32, TSKU, ACER3, B3GNT6, CCDC201, ADCY1, RAMP3, TBRG4, CCM2. Signature of selection analysis revealed multiple candidate genes previously associated with various economic traits. However, BMI genetic variance explained by regions under selection pressure was minimal (1.31%). In conclusion, candidate genes associated with Yorkshire pigs' BMI trait were identified using WssGWAS. Gene enrichment analysis indicated that the identified candidate genes were enriched in the insulin secretion pathway. We anticipate that these results further advance our understanding of the genetic architecture of BMI in Yorkshire pigs and provide information for genomic selection for fat deposition in this breed.
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| 21. |
- Bano, AS, et al.
(författare)
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Genetic and functional characterization of human immunodeficiency virus type 1 VprC variants from north India: presence of unique recombinants with mosaic genomes from B, C and D subtypes within the open reading frame of Vpr
- 2009
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 90:Pt 11, s. 2768-2776
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Tidskriftsartikel (refereegranskat)abstract
- The human immunodeficiency virus type 1 (HIV-1) epidemic in India is predominantly caused by genetic subtype C, though other minor subtypes have also been reported. One of the major accessory proteins of HIV-1, namely Vpr, is known to influence key steps in viral replication, cell cycle progression, promoter activation, apoptosis and pathogenesis. Therefore, we carried out a genetic and functional analysis of the Vpr variants from eight HIV-1-infected individuals from north India. The sequence analyses revealed that six of eight samples clustered with ancestral subtype C. Remarkably, five of these showed a conserved and region-specific L64P mutation, located in the predicted third α-helix. This change adversely affected their ability to activate the HIV-1 long terminal repeat promoter without compromising their ability to cause apoptosis. Bootscan, phylogenetic and SimPlot analysis of the remaining two samples (VprS2 and A6) revealed very interesting mosaic genomes derived from B, C and D subtypes. The N-terminal half of the VprS2 gene consisted of genomic segments derived from subtypes B/D, C and D but the C-terminal half was derived predominantly from subtype C. Interestingly the N-terminal half of sample A6 also showed similar B/D, C and D inter-subtype recombinant structure but the C-terminal half was entirely derived from the consensus B subtype. Multiple breakpoints in a short stretch of 291 nt encoding the Vpr gene strongly suggest that this region is a potential hot-spot for the formation of inter-subtype recombinants and also highlight the importance of the rapidly evolving HIV-1 epidemic in the north Indian region due to multiple genetic subtypes.
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| 22. |
- 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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| 23. |
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| 24. |
- Benkő, Mária, et al.
(författare)
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ICTV Virus Taxonomy Profile : Adenoviridae 2022
- 2022
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 103:3
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Tidskriftsartikel (refereegranskat)abstract
- The family Adenoviridae includes non-enveloped viruses with linear dsDNA genomes of 25-48 kb and medium-sized icosahedral capsids. Adenoviruses have been discovered in vertebrates from fish to humans. The family is divided into six genera, each of which is more common in certain animal groups. The outcome of infection may vary from subclinical to lethal disease. This is a summary of the ICTV Report on the family Adenoviridae, which is available at ictv.global/report/adenoviridae.
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| 25. |
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| 26. |
- Bererhi, Badreddine, et al.
(författare)
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Limited effects of inbreeding on breeding coloration
- 2023
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Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 114:2, s. 143-151
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Tidskriftsartikel (refereegranskat)abstract
- Animal color signals may function as indicators of fighting ability when males compete for access to females. This allows opponents to settle aggressive interactions before they escalate into physical combat and injury. Thus, there may be strong directional selection on these traits, toward enhanced signal quality. This renders sexually selected traits particularly susceptible to inbreeding depression, due to relatively low ratios of additive genetic variance to dominance variance. We measured the effects of inbreeding on an intrasexually selected color signal (the badge) in a population of Swedish sand lizards (Lacerta agilis) using the Rhh software based on 17 to 21 microsatellites. Males of this sexually dichromatic species use the badge during aggressive interactions to display, and assess, fighting ability. We found negative effects of homozygosity on badge size, saturation, and brightness. However, no such effects were observed on color hue. Pairwise correlations between badge size, hue, and saturation were all statistically significant. Thus, the sand lizard "badge" is a multicomponent signal with variation explained by covariation in badge size, saturation, and color hue. Body mass corrected for skeletal size (body condition) positively predicted badge size and saturation, encouraging future research on the extent that sexual signals may convey information on multigene targets (i.e. "genic capture").
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| 27. |
- 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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| 28. |
- Bindra, Amarinder, et al.
(författare)
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Search for DNA of exogenous mouse mammary tumor virus-related virus in human breast cancer samples
- 2007
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 88, s. 1806-1809
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Tidskriftsartikel (refereegranskat)abstract
- Earlier reports of a human exogenous retrovirus (HMTV) related closely to mouse mammary tumor virus (MMTV) led us to search for these viral sequences in breast cancer tissues and normal tissues. A real-time PCR was developed based on MMTV and published HMTV envelope sequences. The real-time PCR method can detect one to ten copies of MMTV target DNA. Tissue samples were collected prospectively from 18 breast cancer patients and 11 non-malignant control cases, as well as peripheral blood leukocytes from the same women. Despite the high sensitivity of the real-time PCR method used, none of the samples were positive for HMTV DNA or RNA. The absence of HMTV DNA in both breast cancer samples and controls indicates either that the concentration of putative HMTV DNA in the breast cancers was too low for detection or that it did not exist there.
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| 29. |
- Bjorling, E, et al.
(författare)
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Human neutralizing human immunodeficiency virus type 2-specific Fab molecules generated by phage display
- 1999
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 8080 ( Pt 8), s. 1987-1993
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Tidskriftsartikel (refereegranskat)abstract
- A panel of human immunodeficiency virus type 2 (HIV-2)-neutralizing, recombinant Fab fragments was generated by using the phage display technique. The combinatorial library was derived from an asymptomatic, HIV-2-seropositive individual and constructed on the surface of filamentous phage by using the pComb3 phagemid vector and then screened against native HIV-2 envelope glycoprotein (gp125). Ten of 30 Fab fragments generated displayed strong reactivity in an ELISA and were therefore selected for further study. Six of these possessed neutralizing capacity, with titres varying from 20 to 80 against the homologous HIV-2 strain, and one also had a weak neutralizing capacity against a heterologous HIV-2 isolate, K135. Sequencing of the heavy chain CDR3 regions showed that the gp125-specific Fabs represented individual clones. These reagents may be useful for studies on the conformational structures of the HIV-2 envelope antigens and their immunogenicity, which may help in vaccine design. Furthermore, the cloned Fab genes may be transformed into whole IgG for eukaryotic expression, and as such used for therapeutic and immunoprophylactic studies in HIV-2-infected macaques and, possibly, for human immunoprophylaxis against HIV-2.
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| 30. |
- 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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| 31. |
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| 32. |
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| 33. |
- 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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| 34. |
- 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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| 35. |
- Brandsch, Roderich, et al.
(författare)
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Expression and flavinylation of Arthrobacter oxydans 6-hydroxy-D-nicotine oxidase in Bacillus subtilis
- 1989
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Ingår i: Journal of General Microbiology. - : Microbiology Society. - 0022-1287. ; 135:1093-1099
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Tidskriftsartikel (refereegranskat)abstract
- 6-Hydroxy-d-nicotine oxidase (6-HDNO) of Arthrobacter oxydans, an enzyme inducible by dl-nicotine, contains FAD covalently bound via an 8α-N(3)His linkage. Expression of the gene encoding 6-HDNO and flavinylation of the protein were studied in Bacillus subtilis. In this heterologous system the following findings were made. 1. An enzymically active covalently flavinylated 6-HDNO of normal size can be expressed in B. subtilis. 2. The natural promoter of the 6-HDNO gene appeared inefficient in B. subtilis. The B. subtilis sdh promoter, when inserted upstream of the A. oxydans promoter, increased 6-HDNO expression >50-fold. 3. Expression of the 6-HDNO gene from plasmids in B. subtilis was, independently of the promoter construct used, stimulated more than fivefold by dl-nicotine in the growth medium. It is concluded that flavinylation of 6-HDNO is possibly autocatalytic and mediated by factors generally found in bacterial cells.
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| 36. |
- 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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| 37. |
- Brinster, C, et al.
(författare)
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Hepatitis C virus non-structural protein 3-specific cellular immune responses following single or combined immunization with DNA or recombinant Semliki Forest virus particles
- 2002
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 83:Pt 2, s. 369-381
-
Tidskriftsartikel (refereegranskat)abstract
- The capacity of recombinant Semliki Forest virus particles (rSFV) expressing the hepatitis C virus non-structural protein 3 (NS3) to induce, in comparison or in combination with an NS3-expressing plasmid, specific cellular and humoral immune responses in murine models was evaluated. In vitro studies indicated that both types of vaccine expressed the expected size protein, albeit with different efficacies. The use of mice transgenic for the human HLA-A2.1 molecule indicated that the rSFV-expressed NS3 protein induces, as shown previously for an NS3 DNA vaccine, NS3-specific cytotoxic lymphocytes (CTLs) targeted at one dominant HLA-A2 epitope described in infected patients. All DNA/rSFV vaccine combinations evaluated induced specific CTLs, which were detectable for up to 31 weeks after the first injection. Overall, less than 1 log difference was observed in terms of the vigour of the bulk CTL response induced and the CTL precursor frequency between all vaccines (ranging from 1:2·6×105 to 1:1×106). Anti-NS3 antibodies could only be detected following a combined vaccine regimen in non-transgenic BALB/c mice. In conclusion, rSFV particles expressing NS3 are capable of inducing NS3-specific cellular immune responses targeted at a major HLA-A2 epitope. Such responses were comparable to those obtained with a DNA-based NS3 vaccine, whether in the context of single or combined regimens.
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| 38. |
- Cao, TH, et al.
(författare)
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Characterization of HLA DR13-restricted CD4(+) T cell epitopes of hepatitis B core antigen associated with self-limited, acute hepatitis B
- 2002
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 83:Pt 12, s. 3023-3033
-
Tidskriftsartikel (refereegranskat)abstract
- The HLA DR13 allele has been associated with a self-limited course of hepatitis B virus infection, possibly through the induction of a more vigorous hepatitis B core antigen (HBcAg) and/or hepatitis B e antigen-specific CD4+ T cell response. HBcAg-specific CD4+ T cell responses were investigated in three HLA DR13-positive subjects with self-limited, acute hepatitis B. HBcAg-specific, short-term T cell lines derived from these three subjects showed a dominant recognition of HBcAg peptides spanning aa 1–20 (P1), 11–30 (P2), 41–60 (P5), 111–131 (P12) and 141–160 (P15). In order to characterize these epitopes in more detail, CD4+ T cell clones and cell lines were generated using HBcAg. Surprisingly, 11 of 12 T cell clones examined recognized P15; one recognized P10 (aa 91–111). Of four T cell lines, two recognized P15 and two recognized P5. By peptide mapping, the minimal epitope of P15 was located to residues 147TVVRRRGRSP156.
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| 39. |
- Carlborg, Örjan, et al.
(författare)
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Parallel computing in interval mapping of quantitative trait loci.
- 2002
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Ingår i: Journal of Heredity. - 0022-1503 .- 1465-7333. ; 92:5
-
Tidskriftsartikel (refereegranskat)abstract
- Linear regression analysis is considered the least computationally demanding method for mapping quantitative trait loci (QTL). However, simultaneous search for multiple QTL, the use of permutations to obtain empirical significance thresholds, and larger experimental studies significantly increase the computational demand. This report describes an easily implemented parallel algorithm, which significantly reduces the computing time in both QTL mapping and permutation testing. In the example provided, the analysis time was decreased to less than 15% of a single processor system by the use of 18 processors. We indicate how the efficiency of the analysis could be improved by distributing the computations more evenly to the processors and how other ways of distributing the data facilitate the use of more processors. The use of parallel computing in QTL mapping makes it possible to routinely use permutations to obtain empirical significance thresholds for multiple traits and multiple QTL models. It could also be of use to improve the computational efficiency of the more computationally demanding QTL analysis methods.
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| 40. |
- Catania, Francesco, et al.
(författare)
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Endogenous Mechanisms for the Origins of Spliceosomal Introns
- 2009
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Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 100:5, s. 591-596
-
Tidskriftsartikel (refereegranskat)abstract
- Over 30 years since their discovery, the origin of spliceosomal introns remains uncertain. One nearly universally accepted hypothesis maintains that spliceosomal introns originated from self-splicing group-II introns that invaded the uninterrupted genes of the last eukaryotic common ancestor (LECA) and proliferated by “insertion” events. Although this is a possible explanation for the original presence of introns and splicing machinery, the emphasis on a high number of insertion events in the genome of the LECA neglects a considerable body of empirical evidence showing that spliceosomal introns can simply arise from coding or, more generally, nonintronic sequences within genes. After presenting a concise overview of some of the most common hypotheses and mechanisms for intron origin, we propose two further hypotheses that are broadly based on central cellular processes: 1) internal gene duplication and 2) the response to aberrant and fortuitously spliced transcripts. These two nonmutually exclusive hypotheses provide a powerful way to explain the establishment of spliceosomal introns in eukaryotes without invoking an exogenous source.
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| 41. |
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| 42. |
- 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
-
Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 110, s. 830-843
-
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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| 43. |
- Clevestig, P, et al.
(författare)
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CCR5 use by human immunodeficiency virus type 1 is associated closely with the gp120 V3 loop N-linked glycosylation site
- 2006
-
Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 87:Pt 3, s. 607-612
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Tidskriftsartikel (refereegranskat)abstract
- Human immunodeficiency virus type 1 (HIV-1) enters cells through the chemokine receptors CCR5 (R5 virus) and/or CXCR4 (X4 virus). Loss of N-linked glycans and increased net charge of the third variable loop (V3) of the gp120 envelope glycoprotein have been observed to be important steps towards CXCR4 use. All reported sequences using CCR5 or CXCR4 exclusively, or using both, were gathered from the Los Alamos HIV Database and analysed with regard to the V3 N-linked glycosylation motifs (sequons) and charge. The V3 loop glycan had a sensitivity of 0·98 and a 0·92 positive predictive value in the context of CCR5 use. The difference from X4 was remarkable (P<10−12). Especially, the sequon motif NNT within the V3 loop was conserved in 99·2 % of the major clades. The results suggest a close association between the V3 loop glycan and CCR5 use and may provide new insight into HIV-1 tropism and help to improve phenotype-prediction models.
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| 44. |
- Coffin, John, et al.
(författare)
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ICTV Virus Taxonomy Profile : Retroviridae 2021
- 2021
-
Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 102:12
-
Tidskriftsartikel (refereegranskat)abstract
- Viruses in the family Retroviridae are found in a wide variety of vertebrate hosts. Enveloped virions are 80-100 nm in diameter with an inner core containing the viral genome and replicative enzymes. Core morphology is often characteristic for viruses within the same genus. Replication involves reverse transcription and integration into host cell DNA, resulting in a provirus. Integration into germline cells can result in a heritable provirus known as an endogenous retrovirus. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Retroviridae, which is available at ictv.global/ report/retroviridae.
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| 45. |
- Collins, Lesley J., et al.
(författare)
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The Modern RNP World of Eukaryotes
- 2009
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Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 100:5, s. 597-604
-
Forskningsöversikt (refereegranskat)abstract
- Eukaryote gene expression is mediated by a cascade of RNA functions that regulate, process, store, transport, and translate RNA transcripts. The RNA network that promotes this cascade depends on a large cohort of proteins that partner RNAs; thus, the modern RNA world of eukaryotes is really a ribonucleoprotein (RNP) world. Features of this "RNP infrastructure" can be related to the high cytosolic density of macromolecules and the large size of eukaryote cells. Because of the densely packed cytosol or nucleoplasm (with its severe restriction on diffusion of macromolecules), partitioning of the eukaryote cell into functionally specialized compartments is essential for efficiency. This necessitates the association of RNA and protein into large RNP complexes including ribosomes and spliceosomes. This is well illustrated by the ubiquitous spliceosome for which most components are conserved throughout eukaryotes and which interacts with other RNP-based machineries. The complexes involved in gene processing in modern eukaryotes have broad phylogenetic distributions suggesting that the common ancestor of extant eukaryotes had a fully evolved RNP network. Thus, the eukaryote genome may be uniquely informative about the transition from an earlier RNA genome world to the modern DNA genome world.
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| 46. |
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| 47. |
- Curr, Kenneth, et al.
(författare)
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Influence of naturally occurring insertions in the fingers subdomain of human immunodeficiency virus type 1 reverse transcriptase on polymerase fidelity and mutation frequencies in vitro
- 2006
-
Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 87, s. 419-428
-
Tidskriftsartikel (refereegranskat)abstract
- The fingers subdomain of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a hotspot for nucleoside analogue resistance mutations. Some multi-nucleoside analogue-resistant variants contain a T69S substitution along with dipeptide insertions between residues 69 and 70. This set of mutations usually co-exists with classic zidovudine-resistance mutations (e.g. M41L and T215Y) or an A62V mutation and confers resistance to multiple nucleoside analogue inhibitors. As insertions lie in the vicinity of the dNTP-binding pocket, their influence on RT fidelity was investigated. Commonly occurring insertion mutations were selected, i.e. T69S-AG, T69S-SG and T69S-SS alone, in combination with 3'-azido-2',3'-deoxythymidine-resistance mutations M41L, L210W, R211K, L214F, T215Y (LAG(AZ) and LSG(AZ)) or with an alternate set where A62V substitution replaces M41L (VAG(AZ), VSG(AZ) and VSS(AZ)). Using a lacZalpha gapped duplex substrate, the forward mutation frequencies of recombinant wild-type and mutant RTs bearing each of the above sets of mutations were measured. All of the mutants displayed significant decreases in mutation frequencies. Whereas the dipeptide insertions alone showed the least decrease (4.0- to 7.5-fold), the VAG series showed an intermediate reduction (5.0- to 11.4-fold) and the LAG set showed the largest reduction in mutation frequencies (15.3- and 16.3-fold for LAG(AZ) and LSG(AZ), respectively). Single dNTP exclusion assays for mutants LSG(AZ) and LAG(AZ) confirmed their large reduction in misincorporation efficiencies. The increased in vitro fidelity was not due to excision of the incorrect nucleotide via ATP-dependent removal. There was also no direct correlation between increased fidelity and template-primer affinity, suggesting a change in the active site that is conducive to better discrimination during dNTP insertion.
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| 48. |
- de Jong, Marein A. W. P., et al.
(författare)
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Dendritic cells mediate herpes simplex virus infection and transmission through the C-type lectin DC-SIGN
- 2008
-
Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 89, s. 2398-2409
-
Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DCs) are essential for the induction of specific immune responses against invading pathogens. Herpes simplex virus (HSV) is a common human pathogen that causes painful but mild infections of the skin and mucosa, and which results in latency and recurrent infections. Of the two HSV subtypes described, HSV-1 causes mainly oral–facial lesions, whilst HSV-2 is associated with genital herpes. DCs are involved in HSV-induced immune suppression, but little is known about the molecular interactions between DCs and HSV. This study demonstrated that HSV-1 and -2 both interact with the DC-specific C-type lectin DC-SIGN. Further analyses demonstrated that DC-SIGN interacts with the HSV glycoproteins gB and gC. Binding of HSV-1 to immature DCs depended on both DC-SIGN and heparan sulfate proteoglycans. Strikingly, HSV-1 infection of DCs was almost completely inhibited by blocking antibodies against DC-SIGN. Thus, DC-SIGN is an important attachment receptor for HSV-1 on immature DCs and enhances infection of DCs in cis. In addition, DC-SIGN captures HSV-1 for transmission to permissive target cells. These data strongly suggest that DC-SIGN is a potential target to prevent HSV infection and virus dissemination. Further studies will show whether these interactions are involved in HSV-induced immune suppression.
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| 49. |
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| 50. |
- 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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