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Edman, Kjell
Publications (10 of 15) Show all publications
Bergman, I. M., Edman, K., van As, P., Huisman, A. & Juul-Madsen, H. R. (2014). A two-nucleotide deletion renders the mannose-binding lectin 2 (MBL2) gene nonfunctional in Danish Landrace and Duroc pigs. Immunogenetics, 66(3), 171-184
Open this publication in new window or tab >>A two-nucleotide deletion renders the mannose-binding lectin 2 (MBL2) gene nonfunctional in Danish Landrace and Duroc pigs
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2014 (English)In: Immunogenetics, ISSN 0093-7711, E-ISSN 1432-1211, Vol. 66, no 3, p. 171-184Article in journal (Refereed) Published
Abstract [en]

The mannose-binding lectins (MBLs) are central components of innate immunity, facilitating phagocytosis and inducing the lectin activation pathway of the complement system. Previously, it has been found that certain single-nucleotide polymorphisms (SNPs) in porcine MBL1 and MBL2 (pMBL1, pMBL2) affect mRNA expression, serum concentration, and susceptibility to disease, but the combinatory effect of pMBL1 and pMBL2 genotypes needs further elucidation. In the present study, pMBL1 and pMBL2 alleles, combined pMBL haplotypes, and MBL-A concentration in serum were analyzed in purebred Landrace (N = 30) and Duroc (N = 10) pigs. Furthermore, the combined pMBL haplotypes of 89 PiStrain x (Large White x Landrace) crossbred pigs were studied, and the genotypes of 67 crossbreds challenged with Escherichia coli were compared to their individual disease records. In the purebred animals, three non-synonymous SNPs and a two-nucleotide deletion were detected in the coding sequence of pMBL2. The two-nucleotide deletion was present at a frequency of 0.88 in the Landrace pigs and 0.90 in the Duroc pigs, respectively. In the crossbreds, the T allele of the SNP G949T in pMBL1-previously shown to have profound effect on MBL-A concentration even in the heterozygote condition-was detected in 47 % of the animals. Finally, an association was found between low-producing MBL genotypes and low body weight on the day of weaning in the same animals.

Keywords
Mannose-binding lectin (MBL), Pigs, Polymorphism, Innate immunity, E. coli, Disease resistance
National Category
Biochemistry and Molecular Biology
Research subject
Natural Science, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-33346 (URN)10.1007/s00251-014-0758-5 (DOI)000331714200004 ()2-s2.0-84894556948 (Scopus ID)
Available from: 2014-03-27 Created: 2014-03-27 Last updated: 2017-12-05Bibliographically approved
Israelsson, S., Sävneby, A., Ekström, J.-O., Jonsson, N., Edman, K. & Lindberg, A. M. (2014). Improved replication efficiency of echovirus 5 after transfection of colon cancer cells using an authentic 5' RNA genome end methodology. Investigational new drugs, 32(6), 1063-1070
Open this publication in new window or tab >>Improved replication efficiency of echovirus 5 after transfection of colon cancer cells using an authentic 5' RNA genome end methodology
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2014 (English)In: Investigational new drugs, ISSN 0167-6997, E-ISSN 1573-0646, Vol. 32, no 6, p. 1063-1070Article in journal (Refereed) Published
Abstract [en]

Oncolytic virotherapy is a promising novel form of cancer treatment, but the therapeutic efficiency needs improvement. A potential strategy to enhance the therapeutic effect of oncolytic viruses is to use infectious nucleic acid as therapeutic agent to initiate an oncolytic infection, without administrating infectious viral particles. Here we demonstrate improved viral replication activation efficiency when transfecting cells with 5’ end authentic in vitro transcribed enterovirus RNA as compared to genomic RNA with additional non-genomic 5’ nucleotides generated by conventional cloning methods. We used echovirus 5 (E5) as an oncolytoc model virus due to its ability to replicate in and completely destroy five out of six colon cancer cell lines and kill artificial colon cancer tumors (HT29 spheroids), as shown here. An E5 infectious cDNA clone including a hammerhead ribozyme sequence was used to generate in vitro transcripts with native 5’ genome ends. In HT29 cells, activation of virus replication is approximately 20-fold more efficient for virus genome transcripts with native 5’ genome ends compared to E5 transcripts generated from a standard cDNA clone. This replication advantage remains when viral progeny release starts by cellular lysis 22 h post transfection. Hence, a native 5’ genomic end improves infection activation efficacy of infectious nucleic acid, potentially enhancing its therapeutic effect when used for cancer treatment. The clone design with a hammerhead ribozyme is likely to be applicable to a variety of oncolytic positive sense RNA viruses for the purpose of improving the efficacy of oncolytic virotherapy.

Keywords
Picornavirus, RNA virus, Enterovirus, Oncolytic virotherapy, Hammerhead ribozyme, Infectious nucleic acid
National Category
Biochemistry and Molecular Biology
Research subject
Biomedical Sciences, Virology
Identifiers
urn:nbn:se:lnu:diva-41541 (URN)10.1007/s10637-014-0136-z (DOI)000345142300002 ()2-s2.0-84938677294 (Scopus ID)
Available from: 2015-04-01 Created: 2015-04-01 Last updated: 2017-12-04Bibliographically approved
Bergman, I.-M., Edman, K., Nilsson Ekdahl, K., Rosengren, K. J. & Edfors, I. (2012). Extensive polymorphism in the porcine Toll-like receptor 10 gene. International Journal of Immunogenetics, 39(1), 68-76
Open this publication in new window or tab >>Extensive polymorphism in the porcine Toll-like receptor 10 gene
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2012 (English)In: International Journal of Immunogenetics, ISSN 1744-3121, E-ISSN 1744-313X, Vol. 39, no 1, p. 68-76Article in journal (Refereed) Published
Abstract [en]

The great importance of the Toll-like receptors (TLRs) in innate immunity is well established, but one family member – TLR10 – remains elusive. TLR10 is expressed in various tissues in several species, but its ligand is not known and its function is still poorly understood. The open reading frame of TLR10 was sequenced in 15 wild boars, representing three populations, and in 15 unrelated domestic pigs of Hampshire, Landrace and Large White origin. Amino acid positions corresponding to detected nonsynonymous single nucleotide polymorphisms (SNPs) were analysed in the crystal structures determined for the human TLR1–TLR2–lipopeptide complex and the human TLR10 Toll/Interleukin 1 receptor (TIR) dimer. SNP occurrence in wild boars and domestic pigs was compared, and haplotypes for the TLR10 gene and the TLR6-1-10 gene cluster were reconstructed. Despite the limited number of animals sequenced in the present study (N = 30), a larger number of SNPs were found in TLR10 than recently reported for TLR1, TLR6 and TLR2. Thirty-three SNPs were detected, of which 20 were nonsynonymous. The relative frequency of nonsynonymous (dN) and synonymous (dS) SNPs between wild boars and domestic pigs was higher in TLR10 than recently reported for TLR1, TLR6 and TLR2. However, the polymorphism reported in the present study seems to leave the function of the TLR10 molecule unaffected. Furthermore, no nonsynonymous SNPs were detected in the part of the gene corresponding to the hinge region of the receptor, probably reflecting rigorously acting functional constraint. The total number of SNPs and the number of nonsynonymous SNPs were significantly lower (< 0.05) in the wild boars than in the domestic pigs, and fewer TLR10 haplotypes were present in the wild boars. The majority of the TLR6-1-10 haplotypes were specific for either wild boars or domestic pigs, probably reflecting differences in microbial environment and population history.

National Category
Immunology Genetics
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-15033 (URN)10.1111/j.1744-313X.2011.01057.x (DOI)2-s2.0-84855348173 (Scopus ID)
Available from: 2011-10-19 Created: 2011-10-19 Last updated: 2017-12-08Bibliographically approved
Bergman, I.-M., Rosengren, K. J., Edman, K. & Edfors, I. (2010). European wild boars and domestic pigs display different polymorphic patterns in the Toll-like receptor (TLR) 1, TLR2, and TLR6 genes. Immunogenetics, 62(1), 49-58
Open this publication in new window or tab >>European wild boars and domestic pigs display different polymorphic patterns in the Toll-like receptor (TLR) 1, TLR2, and TLR6 genes
2010 (English)In: Immunogenetics, ISSN 0093-7711, E-ISSN 1432-1211, Vol. 62, no 1, p. 49-58Article in journal (Refereed) Published
Abstract [en]

During the last decade, the Toll-like receptors (TLRs) have been extensively studied and their immense importance in innate immunity is now being unveiled. Here, we report pronounced differences – probably reflecting the domestication process and differences in selective pressure – between wild boars and domestic pigs regarding single nucleotide polymorphisms (SNPs) in TLR genes. The open reading frames of TLR1, TLR2, and TLR6 were sequenced in 25 wild boars, representing three populations, and in 15 unrelated domestic pigs of Hampshire, Landrace, and Large White origin. In total, 20, 27, and 26 SNPs were detected in TLR1, TLR2, and TLR6, respectively. In TLR1 and TLR2, the numbers of SNPs detected were significantly lower (P ≤ 0.05, P ≤ 0.01) in the wild boars than in the domestic pigs. In the wild boars, one major high frequency haplotype was found in all three genes, while the same pattern was exhibited only by TLR2 in the domestic pigs. The relative frequency of non-synonymous (dN) and synonymous (dS) SNPs was lower for the wild boars than for the domestic pigs in all three genes. In addition, differences in diversity between the genes were revealed: the mean heterozygosity at the polymorphic positions was markedly lower in TLR2 than in TLR1 and TLR6. Because of its localization – in proximity of the bound ligand – one of the non-synonymous SNPs detected in TLR6 may represent species-specific function on the protein level. Furthermore, the codon usage pattern in the genes studied deviated from the general codon usage pattern in Sus scrofa.

Place, publisher, year, edition, pages
Springer, 2010
Keywords
polymorphism, Toll-like receptor (TLR), selection, swine, codon usage
National Category
Genetics
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-107 (URN)10.1007/s00251-009-0409-4 (DOI)
Available from: 2010-03-17 Created: 2010-03-17 Last updated: 2017-12-12Bibliographically approved
Bergman, I.-M., Edman, K., Rosengren, K. J. & Edfors, I. (2010). European wild boars and domestic pigs display different polymorphic patterns in the Toll-like receptor (TLR)1, TLR2, TLR6, and TLR10 genes.. In: International Symposium on Animal Genomics for Animal Health Paris, France, 31 May – 2 June 2010: The AGAH 2010 Abstract Book. Paper presented at International Symposium on Animal Genomics for Animal Heallth, Paris, 31 maj-2 juni, 2010 (pp. 35).
Open this publication in new window or tab >>European wild boars and domestic pigs display different polymorphic patterns in the Toll-like receptor (TLR)1, TLR2, TLR6, and TLR10 genes.
2010 (English)In: International Symposium on Animal Genomics for Animal Health Paris, France, 31 May – 2 June 2010: The AGAH 2010 Abstract Book, 2010, p. 35-Conference paper, Published paper (Other academic)
Abstract [en]

The Toll-like receptors (TLR) are vitally important pattern recognition receptors linking innate and adaptive immunity. Several single nucleotide polymorphisms (SNP) in human TLR genes have been associated with disease. There are few studies on associations between polymorphisms in TLR genes and disease in pigs, but the TLR2/TLR6 heterodimer is activated by Mycoplasma hyopneumoniae, and the expression of TLR2, TLR4, and TLR9 is modulated in the presence of different Salmonella serovars. Porcine TLR1, TLR6, and TLR10 are located in a cluster on the p arm of chromosome 8, while TLR2 resides on the q arm. Previously, we identified quantitative trait loci (QTL) for immune-related traits on pig chromosome 8, close to the KIT gene and the microsatellite S0225, respectively. In order to explore polymorphism in some TLR genes in European wild boars and domestic pigs, TLR1, TLR2, and TLR6 were sequenced in 25 wild boars, representing three populations, and in 15 domestic pigs of Hampshire, Landrace, and Large White origin. Similarly, TLR10 was sequenced in 15 wild boars and 15 domestic pigs. In TLR1 and TLR2, more SNP were present in the domestic pigs than in the wild boars. In TLR6, SNP numbers were similar in both animal groups, but the level of heterozygosity was higher in the domestic pigs than in the wild boars. In TLR10, again, more SNP were present in the domestic pigs, and a higher number of nonsynonymous SNP were detected in TLR10 compared to the other genes. This may suggest redundancy for TLR10 in pigs. 

National Category
Genetics Medical Bioscience
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-7426 (URN)
Conference
International Symposium on Animal Genomics for Animal Heallth, Paris, 31 maj-2 juni, 2010
Available from: 2010-08-17 Created: 2010-08-17 Last updated: 2014-02-25Bibliographically approved
Israelsson, S., Gullberg, M., Jonsson, N., Roivainen, M., Edman, K. & Lindberg, A. M. (2010). Studies of Echovirus 5 interactions with the cell surface: Heparan sulfate mediates attachment to the host cell.. Virus Research, 151(2), 170-176
Open this publication in new window or tab >>Studies of Echovirus 5 interactions with the cell surface: Heparan sulfate mediates attachment to the host cell.
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2010 (English)In: Virus Research, ISSN 0168-1702, E-ISSN 1872-7492, Vol. 151, no 2, p. 170-176Article in journal (Refereed) Published
Abstract [en]

Infections caused by Echovirus 5 (E5), an enterovirus of the Picornaviridae family, have been associated with fever, rashes and sporadic cases of aseptic meningitis. To elucidate the receptor usage of this virus, the significance of a previously proposed integrin binding arginine-glycine-aspartic acid (RGD) motif found in the VP3 capsid protein was investigated, as well as the capacity of E5 to interact with heparan sulfate on the cell surface. Using the prototype strain E5 Noyce (E5N), an E5N mutant where the aspartic acid of the RGD motif has been substituted to a glutamic acid and clinical E5 isolates, the RGD motif of VP3 was found to be non-essential and hence not involved in integrin receptor binding. However, E5N and clinical E5 isolates interact with heparan sulfate at the cell surface, as demonstrated by virus replication inhibition assays using heparin and heparinase III, and studies of E5 interactions at the cell surface measured by real-time PCR analysis. In conclusion, E5 utilizes heparan sulfate as a cellular receptor, but the RGD motif of VP3 is not essential for E5 infectivity.

National Category
Microbiology in the medical area
Research subject
Biomedical Sciences, Virology
Identifiers
urn:nbn:se:lnu:diva-7169 (URN)10.1016/j.virusres.2010.05.001 (DOI)20466025 (PubMedID)2-s2.0-77954219093 (Scopus ID)
Available from: 2010-08-13 Created: 2010-08-13 Last updated: 2018-01-12Bibliographically approved
Tolf, C., Ekström, J.-O., Gullberg, M., Arbrandt, G., Niklasson, B., Frisk, G., . . . Lindberg, A. M. (2008). Characterization of polyclonal antibodies against the capsid proteins of Ljungan virus. Journal of Virological Methods, 150(1-2), 34-40
Open this publication in new window or tab >>Characterization of polyclonal antibodies against the capsid proteins of Ljungan virus
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2008 (English)In: Journal of Virological Methods, ISSN 0166-0934, E-ISSN 1879-0984, Vol. 150, no 1-2, p. 34-40Article in journal (Refereed) Published
Abstract [en]

Ljungan virus (LV) is a suspected human pathogen isolated from voles in Sweden and North America. To enable virus detection and studies of localization and activity of virion proteins, polyclonal antibodies were produced against bacterially expressed capsid proteins of the LV strain, 87-012G. Specific detection of proteins corresponding to viral antigens in lysates of LV infected cells was demonstrated by immunoblotting using each one of the generated polyclonal antibodies. In addition, native viral antigens present in cell culture infected with LV strains 87-012G or 145SLG were detected in ELISA and by immunofluorescence using the antibodies against the VP0 and VP1 proteins. The anti-VP3 antibody did not react with native proteins of the LV virion, suggesting that the VP3 is less potent in evoking humoral response and may have a less exposed orientation in the virus capsid. No activity of the antibodies was observed against the closely related human parechovirus type 1. The polyclonal antibody against the VP1 protein was further used for detection of LV infected myocytes in a mouse model of LV-induced myocarditis. Thus, polyclonal antibodies against recombinant viral capsid proteins enabled detection of natural LV virions by several different immunological methods.

Place, publisher, year, edition, pages
Elsevier, 2008
Keywords
Parechovirus, Protein expression, Polyclonal antibodies, Virus detection, Immunodetection
National Category
Microbiology in the medical area
Research subject
Biomedical Sciences, Virology
Identifiers
urn:nbn:se:hik:diva-928 (URN)10.1016/j.jviromet.2008.02.012 (DOI)18403027 (PubMedID)
Available from: 2008-12-11 Created: 2008-12-10 Last updated: 2018-01-13Bibliographically approved
Ekström, J.-O., Tolf, C., Edman, K. & Lindberg, A. M. (2007). Physicochemical properties of the Ljungan virus virion in different environments: inactivated by heat but resistant th acidic pH, detergents, and non-physiological environments such as Virkon® containing soulutions. Microbiology and immunology, 51, 841-850
Open this publication in new window or tab >>Physicochemical properties of the Ljungan virus virion in different environments: inactivated by heat but resistant th acidic pH, detergents, and non-physiological environments such as Virkon® containing soulutions
2007 (English)In: Microbiology and immunology, ISSN 0385-5600, E-ISSN 1348-0421, Vol. 51, p. 841-850Article in journal (Refereed) Published
National Category
Natural Sciences
Research subject
Biomedical Sciences, Virology; Natural Science, Microbiology; Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-1688 (URN)
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2017-12-12Bibliographically approved
Ekström, J.-O., Tolf, C., Fahlgren, C., Johansson, S., Arbrandt, G., Niklasson, B., . . . Lindberg, A. M. (2007). Replication of Ljungan virus in cell culture: The genomic 5'-end, infectious cDNA clones and host cell response to viral infections. Virus Research, 130(December 2007), 129-139
Open this publication in new window or tab >>Replication of Ljungan virus in cell culture: The genomic 5'-end, infectious cDNA clones and host cell response to viral infections
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2007 (English)In: Virus Research, ISSN 0168-1702, E-ISSN 1872-7492, Vol. 130, no December 2007, p. 129-139Article in journal (Refereed) Published
Abstract [en]

Ljungan virus (LV) is a picornavirus recently isolated from bank voles (Clethrionomys glareolus). The previously uncharacterised 5'-end sequence of the LV genome was determined. Infectious cDNA clones were constructed of the wild type LV prototype strain 87-012 and of the cytolytically replicating cell cultureadapted variant 87-012G. Virus generated from cDNA clones showed identical growth characteristics as uncloned virus stocks. Cell culture adapted LV, 87-012G, showed a clear cytopathic effect (CPE) at 3-4 days post-infection (p.i.). Virus titers, determined by plaque titration, increased however only within the first 18 h p.i. Replication of LV (+) strand RNA was determined by real-time PCR and corresponded in time with increasing titers. In contrast, the amounts of thereplication intermediate, the (-) strand, continued to increase until the cells showed CPE. This indicates separate controlling mechanisms for replication of LV (+) and (-) genome strands. Replication was also monitored by immunofluorescence (IF) staining. IF staining of both prototype 87-012 and the CPE causing 87-012G showed groups of 5-25 infected cells at 48 h p.i., suggesting a, for picornaviruses, not previously described direct cell-to-cell transmission.

National Category
Microbiology
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-2358 (URN)10.1016/j.virusres.2007.06.004 (DOI)000251480800015 ()17645978 (PubMedID)
Note

Ingår i avhandling under titeln: "Replication of Ljungan virus in cell culture: properties of the virus-host cell interactions".

Available from: 2010-04-07 Created: 2010-04-07 Last updated: 2017-11-27Bibliographically approved
Johannesson, P., Israelsson, S., Edman, K. & Lindberg, A. M. (2005). A novel and rapid method to quantify cytolytic replication of picornaviruses in cell culture. Journal of virological methods, 130, 117-123
Open this publication in new window or tab >>A novel and rapid method to quantify cytolytic replication of picornaviruses in cell culture
2005 (English)In: Journal of virological methods, Vol. 130, p. 117-123Article in journal (Refereed) Published
Abstract [en]

Determining viral titers is a key issue in a wide variety of studies regarding different aspects of virology. The standard methods used for determining picornavirus titers are endpoint titration assay and plaque assay, both time consuming and laborious. The method described uses the tetrazolium salt MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide) that is reduced to formazane by cellular dehydrogenase, genes shown to be down-regulated during picornavirus infection. The amount formazane produced correlates with the viral titers obtained and can easily be measured using an ELISA plate reader. The colorimetric method has been evaluated using virus types from different genera of the Picornaviridae family. The MTT method reduces the time spent on determining the viral titers and still maintains a reliable accuracy.

National Category
Microbiology in the medical area
Research subject
Biomedical Sciences, Virology; Natural Science, Biomedical Sciences; Natural Science, Microbiology
Identifiers
urn:nbn:se:lnu:diva-564 (URN)10.1016/j.jviromet.2005.06.016 (DOI)
Available from: 2010-04-01 Created: 2010-04-01 Last updated: 2018-01-12Bibliographically approved
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