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A C Svensson

Publications and source records attributed to A C Svensson.

10 recordsLinked to original sources

Chromosomal distribution, localization and expression of the human endogenous retrovirus ERV9.

ERV9 is a class I family of human endogenous retroviral sequences. Somatic cell hybrid genomic hybridization experiments using a mono-chromosomal panel indicate the presence of approximately 120 ERV9 loci in the human genome distributed on most chromosomes. Fluorescence in situ hybridization (FISH) using an ERV9 cDNA probe containing gag, pol and env sequences, verified this observation and a consistent signal was found at the chromosome region 11q13.3-->q13.5. By analysis of a panel of radiation hybrids, an ERV9 locus was mapped to within a 300-kbp region at the chromosome site 11q13. The marker cCLGW567 and the locus MAP3K11/D11S546 centromeric and telomeric flanked it, respectively. Northern blot analysis, using an ERV9 LTR probe, indicated that most normal tissues examined expressed low abundant ERV9 LTR driven mRNAs of various sizes. The most prominent expression was found in adrenal glands and testis. However, the level of expression varied in the same tissues among different individuals indicating that ERV9 mRNA expression probably is inducible in certain tissues or at various cell stages.

Animals↗

Retroelements in the human MHC class II region.

Molecular genetic studies of the human major histocompatibility complex (MHC) have led to the identification of more than 200 genes. Besides the large number of genes in the MHC, densely clustered areas of retroelements have been identified. These include short and long interspersed elements (SINEs and LINEs), and human endogenous retroviruses (HERVs). The presence of retroelements in the MHC provides a clear example of how these elements affect the genome plasticity of the host. Comparative analyses of these retroelements have proven highly useful in evolutionary studies of the MHC. Recently, HERV-encoded superantigens have been implicated as candidate autoimmune genes in type I diabetes and multiple sclerosis. In addition, genetic analyses have revealed that autoimmune diseases show strong associations with MHC class II genes. The intriguing correlations between retroviral encoded antigens, MHC class II genes and the development of autoimmune disease merit intense future investigations of retroelements, in particular those endogenous retroviruses located in the MHC class II region proper.

Antigens↗

Expression of human endogenous retrovirus ERV3 (HERV-R) mRNA in normal and neoplastic tissues.

We investigated the mRNA expression of the human endogenous retrovirus ERV3 (HERV-R) in several normal and corresponding tumor tissues. The env gene of ERV3 is expressed as mRNA in several tissues. Comparison of ERV3 mRNA expression by Northern analyses, revealed a non-systematic variation. Expression was shown to be particularly high in the adrenal gland and some cases of lung cancer. This tissue-tropism should be seen in relation to the high expression previously found in syncytiotrophoblasts in placenta and sebaceous glands of the skin, suggesting profound influences by steroid hormonal regulation.

Blotting, Northern↗

Presence of retroelements reveal the evolutionary history of the human DR haplotypes.

Comparison of intron sequences has been a successful tool for drawing major conclusions about the evolutionary relationship of DRB genes. This complex family of genes is discussed in this review as well as a proposed model for the evolution of HLA-DR haplotypes. The model is based both on phylogenetic analysis of intron sequences as well as presence of ERV9 LTR elements located at identical position in intron 5 of a number of DRB genes. According to this model, two main evolutionary branches of DR haplotypes exist. The DR53 haplotype represents one branch, and the second branch contains the DR51, DR52, DR1, and DR8 haplotypes. After the divergence of the DR53 haplotype, an ERV9 LTR element was inserted in a primordial gene. Consequently, all DRB1 genes as well as the DRB3 gene within haplotypes of the second branch, contain this LTR element. In addition, conserved regulatory sequence motifs are found present within these LTR elements that might regulate DRB gene expression. Novel haplotypes are generated by recombinations and the maintenance of the DR haplotype variation as well as the frequent genetic rearrangements observed might be evolutionary advantageous.

Animals↗

Evolutionary relationship between human major histocompatibility complex HLA-DR haplotypes.

HLA-DR haplotypes of the human major histocompatibility complex are organized in five different groups. They can be identified based on the serological specificity expressed by the polymorphic DRB1 locus and by the presence of a characteristic set of DRB genes. The nucleotide sequences of introns 4 and 5 of the two DRB genes (DRB1(*)01 and DRB6(*)01 ) from a DR1 haplotype and the three DRB genes (DRB1(*)15, DRB6(*)15 , and DRB5(*)15 ), from a DR51 haplotype were determined. This study identified endogenous retroviral long terminal repeat elements (ERV9 LTR) located at identical positions in intron 5 of the DRB1 genes in both the DR1 and DR51 haplotypes. Phylogenetic analyses revealed a close evolutionary relationship between these two haplotypes. The DRB5 gene, unique for the DR51 haplotype, may have been lost by a recent gene deletion event creating the DR1 haplotype. A model for the evolution of the human DR haplotypes involving separate duplication and contraction events is presented.

Base Sequence↗

Primate DRB genes from the DR3 and DR8 haplotypes contain ERV9 LTR elements at identical positions.

The HLA-DRB genes of the human major histocompatibility complex constitute a multigene family with a varying number of DRB genes in different haplotypes. To gain further knowledge concerning the evolutionary relationship, the complete nucleotide sequence was determined for a region spanning introns 4 and 5 of the three DRB genes (DRB1*0301, DRB2, and DRB3*0101) from a DR52 haplotype and the single DRB gene (DRB1*08021) in the DR8 haplotype. These analyses identified as endogenous retroviral long terminal repeat element (ERV9 LTR3), inserted at identical positions in intron 5 of the functional DRB genes in these two haplotypes. Comparison of the nucleotide sequence from introns 4 and 5 including the ERV9 LTR elements revealed a strong similarity between the three expressed DRB genes. The DRB3*0101 and DRB1*08021 genes were most similar in this comparison. These findings provide further evidence for a separate duplication in a primordial DR52 haplotype followed by a gene contraction event in the DR8 haplotype. A homologous element was found in a chimpanzee DRB gene from a DR52 haplotype. This represents the first characterized ERV9 LTR element in a nonhuman species. The corresponding introns of the DRB genes in the DR4 haplotype contain no ERV9 LTRs. In contrast, these genes have insertions of distinct Alu repeats, implying distinct evolutionary histories of DR52 and DR53 haplotypes, respectively. Phylogenetic analyses of DRB introns from DR52, DR53, and DR8 haplotypes showed a close relationship between the DRB2 and DRB4 genes. Thus, the ancestral DR haplotype that evolved to generate the DR52 and DR53 haplotypes most likely shared a primordial common DRB gene.

Animals↗

Characterization of three separated exons in the HLA class II DR region of the human major histocompatibility complex.

The human major histocompatibility complex, HLA, is a highly polymorphic gene region which includes the DRA and DRB genes. The number of DRB genes differs between haplotypes. The DR4 haplotype seems to be one of the most complex with five DRB loci, DRB1, DRB4, DRB7, DRB8, and DRB9, in addition to the single DRA locus. We determined the nucleotide sequences of three separated DRB exons located between the DRB4 locus and the DRA locus in the DR4 haplotype, two DRB signal-peptide exons (S1 and S3) and one DRB first-domain exon (locus designation DRB9). Sequence comparisons suggest the following order of events for the origin of these exons: DRB9 seems to be the oldest exon and has previously been detected in multiple HLA haplotypes. DRB9 is more divergent than the three other known DRB pseudogenes, all of which have been found in apes. This suggests that DRB9 arose prior to the hominoid divergence. An L1 repeat has been inserted 3' to DRB9. Subsequently, a LTR of the ERV9 retrovirus-like family was inserted into the L1 repeat. Such LTRs have recently been observed in some of the other DRB genes. The pseudogenes DRB7 and DRB8 (containing only exons 3-6) arose after DRB9. Finally, the separated signal peptide exons S1 and S3 were formed. The molecular characterization of these separated DRB exons and insertion elements further clarifies the complex evolutionary history of the HLA-DR region. These selectively neutral exons may serve as useful markers for tracing the phylogeny of HLA haplotypes.

Base Sequence↗

The structure of human MHC class II genes.

The class II molecules of the human major histocompatibility complex bind intracellularly processed peptides and present them to T-helper cells. They therefore have a critical role in the initiation of the immune response. A salient feature of the class II molecules is their polymorphism. It has been shown that some autoimmune diseases are associated with certain class II alleles. This article reviews the basic structural features of class II molecules, and the genes encoding them as well as mechanisms governing the development of their extraordinary polymorphism.

Autoimmune Diseases↗

The in-vitro influence of ceftazidime on host defence mechanisms.

The effects of ceftazidime, a new third generation cephalosporin, on host defence mechanisms, was investigated in vitro. No significant alteration of polymorphonuclear leukocyte chemotactic, phagocytic, or chemiluminescent responses were found. Granulocyte adherence to nylon fibre columns was increased by 10 mg/l or more of ceftazidime. Lymphocyte DNA synthesis was slightly decreased by high concentrations of ceftazidime, though not by therapeutic concentrations. Ceftazidime was found to stimulate the release of increased amounts of chemotaxis and phagocytosis-stimulating factors from Escherichia coli and Pseudomonas aeruginosa when bacteria were exposed to subminimal inhibitory concentrations of the antibiotic during active growth phases.

Ceftazidime↗