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- Gullberg, Maria, et al.
(författare)
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A single coxsackievirus B2 capsid residue controls cytolysis and apoptosis in rhabdomyosarcoma cells.
- 2010
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Ingår i: Journal of Virology. - 0022-538X .- 1098-5514. ; 84:12, s. 5868-5879
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Tidskriftsartikel (refereegranskat)abstract
- Coxsackievirus B2 (CVB2), one of six human pathogens of the group B coxsackieviruses within the enterovirus genus of Picornaviridae, causes a wide spectrum of human diseases ranging from mild upper respiratory illnesses to myocarditis and meningitis. The CVB2 prototype strain Ohio-1 (CVB2O) was originally isolated from a patient with summer grippe in the 1950s. Later on, CVB2O was adapted to cytolytic replication in rhabdomyosarcoma (RD) cells. Here, we present analyses of the correlation between the adaptive mutations of this RD variant and the cytolytic infection in RD cells. Using reverse genetics, we identified a single amino acid change within the exposed region of the VP1 protein (glutamine to lysine at position 164) as the determinant for the acquired cytolytic trait. Moreover, this cytolytic virus induced apoptosis, including caspase activation and DNA degradation, in RD cells. These findings contribute to our understanding of the host cell adaptation process of CVB2O and provide a valuable tool for further studies of virus-host interactions.
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| 2. |
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| 3. |
- Sjöberg Wester, Elisabet, et al.
(författare)
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Genetic basis of the K phenotype in the Swedish population.
- 2005
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Ingår i: Transfusion. - : Wiley. - 1537-2995 .- 0041-1132. ; 45:4, s. 545-549
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in Undetermined BACKGROUND: The absence of all Kell blood group antigens (K0 phenotype) is very rare. K0 persons, however, can produce clinically significant anti-Ku (K5) after transfusion and/or pregnancy and require K0 blood for transfusion. Ten alleles giving rise to the K0 phenotype have been reported: different populations were studied although none from Scandinavia. STUDY DESIGN AND METHODS: Three K0 samples were identified by blood banks in Sweden (Uppsala,Umeå, and Linköping) during a 20-year period. Kell antigen typing was performed with standard serologic techniques by the respective blood banks and K 0 status was confirmed by the International Blood GroupReference Laboratory in Bristol, England. Polymerase chain reaction and DNA sequencing of the KEL coding region (exons 1-19) was performed on genomic DNA. RESULTS:The Uppsala K0 was homozygous for a 1540C>T substitution in exon 13, leading to an immediate stop codon. The Umeå K0 was homozygous for 1023delG in exon 8 that results in a frameshift and a premature stop codon in exon 9. In the Linköping K0, a previously reported mutation g>a at +1 of intron 3 was found. CONCLUSION: Two novel and one previously reported null alleles at the KEL locus are described. The identified nonsense mutations abolish expression of the Kell glycoprotein and are thus responsible for the K0 phenotype in these Swedish families.
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| 4. |
- Storry, Jill, et al.
(författare)
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Homozygosity for a null allele of SMIM1 defines the Vel-negative blood group phenotype
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 537-U109
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Tidskriftsartikel (refereegranskat)abstract
- The Vel antigen is present on red blood cells (RBCs) from all humans except rare Vel-negative individuals who can form antibodies to Vel in response to transfusion or pregnancy. These antibodies may cause severe hemolytic reactions in blood recipients. We combined SNP profiling and transcriptional network modeling to link the Vel-negative phenotype to SMIM1, located in a 97-kb haplotype block on chromosome 1p36. This gene encodes a previously undiscovered, evolutionarily conserved transmembrane protein expressed on RBCs. Notably, 35 of 35 Vel-negative individuals were homozygous for a frameshift deletion of 17 bp in exon 3. Functional studies using antibodies raised against SMIM1 peptides confirmed a null phenotype in RBC membranes, and SMIM1 overexpression induced Vel expression. Genotype screening estimated that similar to 1 of 17 Swedish blood donors is a heterozygous deletion carrier and similar to 1 of 1,200 is a homozygous deletion knockout and enabled identification of Vel-negative donors. Our results establish SMIM1 as a new erythroid gene and Vel as a new blood group system.
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