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Biomedical subjects

M Kenter

Publications and source records attributed to M Kenter.

15 recordsLinked to original sources

Canine distemper virus from diseased large felids: biological properties and phylogenetic relationships.

Specific pathogen free (SPF) domestic cats were inoculated with tissue homogenate obtained from a Chinese leopard (Panthera pardus japonensis) that had died in a North American zoo from a natural infection with canine distemper virus (CDV). The cats developed a transient cell-associated CDV viraemia along with pronounced lymphopenia but did not show any clinical symptoms. Plasma neutralizing-antibody titres against the homologous CDV (A92-27/4, isolated from the Chinese leopard) were consistently higher than against the CDV vaccine strain 'Bussell'. The Chinese leopard CDV isolate showed in vitro biological properties reminiscent of virulent, wild-type CDV strains. Sequence analysis of the H gene of two large felid CDV isolates from the USA (A92-27/4 and A92-6) revealed up to 10% amino acid changes including up to four additional potential N-linked glycosylation sites in the extra-cytoplasmic domain as compared to CDV vaccine strains. Phylogenetic analysis was performed using the entire coding region of the H gene and a 388 bp fragment of the P gene of several morbillivirus species. Evidence was obtained that recent CDV isolates from different species in the United States (including isolates from large felids), Europe and Africa are significantly distinct from CDV vaccine strains. All wild-type CDV isolates analysed clustered according to geographical distribution rather than to host species origin. By sequence analysis a CDV epizootic among large felids in a Californian safari park was linked to a virus which most likely originated from feral non-felid carnivores.

Amino Acid Sequence↗

Allelic diversity at the Mhc-DP locus in rhesus macaques (Macaca mulatta).

Allelic diversity at the major histocompatibility complex class II DP locus of rhesus macaques was studied by sequencing exon 2 of Mamu-DPA1 and -DPB1 genes. The Mamu-DPA1 gene is apparently invariant, whereas the Mamu-DPB1 locus displays polymorphism. Here we report the characterization of 1 Mamu-DPA1 and 13 Mamu-DPB1 alleles which were compared with other available primate Mhc-DPA1 and -DPB1 sequences. As compared with Mhc-DRB and -DQB1, most codons for the contact residues in the antigen binding site of the primate Mhc-DPB1 gene have a relatively low degree of variation in encoding various types of amino acids. In contrast to Mhc-DRB and -DQB, the HLA- and Mamu-DPB1 sequences cluster in a species-specific manner in phylogenetic trees. Mhc-DPB1 polymorphisms, however, are inherited in a transspecies mode of evolution, as is demonstrated by the sharing of lineage members between closely related macaque species. The data demonstrate that the transspecies character of Mhc-DPB1 polymorphism was retained over much shorter periods of time as compared with its sister class II loci, Mhc-DQ and -DR.

Alleles↗

Phylogenetic evidence of canine distemper virus in Serengeti's lions.

Recently an epizootic, reported to be due to a morbillivirus infection, affected the lion population of the Tanzanian Serengeti National Park. A morbillivirus phosphoprotein (P) gene fragment was amplified by PCR from tissue samples of several affected lions. Sequencing of the amplificates and subsequent phylogenetic analyses revealed that a wild-type strain of canine distemper morbillivirus (CDV) was involved. Vaccination of the local domestic dog population with proven safe CDV vaccines is proposed.

Animals↗

Comparative analysis of the gene encoding the nucleocapsid protein of dolphin morbillivirus reveals its distant evolutionary relationship to measles virus and ruminant morbilliviruses.

A morbillivirus of uncertain origin recently killed hundreds of Mediterranean dolphins. This is the first report of the nucleotide and deduced amino acid sequence of a dolphin morbillivirus (DMV) gene. The sequence of the nucleocapsid (N) gene including boundaries was determined. When the DMV N gene coding region was compared with the corresponding sequences of other morbilliviruses a distant evolutionary relationship between these viruses and DMV was apparent. Phylogenetic analysis of the sequence data provided further evidence that DMV is not closely related to any known morbillivirus, whereas phocine distemper virus exhibits a relatively close relationship to canine distemper virus.

Amino Acid Sequence↗

Insertion of N-linked glycosylation sites in the variable regions of the human immunodeficiency virus type 1 surface glycoprotein through AAT triplet reiteration.

Variable regions with sequence length variation in the human immunodeficiency virus type 1 envelope exhibit an unusual pattern of codon usage with AAT, ACT, and AGT together composing > 70% of all codons used. We postulate that this distribution is caused by insertion of AAT triplets followed by point mutations and selection. Accumulation of the encoded amino acids (asparagine, serine, and threonine) leads to the creation of new N-linked glycosylation sites, which helps the virus to escape from the immune pressure exerted by virus-neutralizing antibodies.

Base Sequence↗

Mhc-DRB and -DQA1 nucleotide sequences of three lowland gorillas. Implications for the evolution of primate Mhc class II haplotypes.

Mhc-DRB and -DQA1 second-exon and -DRB 3'-untranslated-region nucleotide sequences of three lowland gorillas with no known family relationship with each other and of two HLA homozygous typing cell lines were determined and compared with published primate Mhc-DRB and -DQA1 sequences. Eleven distinct MhcGogo-DRB second-exon sequences were found, which represent the gorilla counterparts of the HLA-DRB1*03, -DRB1*10, -DRB3, -DRB5, and -DRB6 allelic lineages. One Gogo-DRB second-exon sequence does not have an obvious human counterpart and is tentatively designated Gogo-DRBY*01. The gorilla equivalents of the HLA-DRB2 and -DRB8 loci were identified as judged on Mhc-DRB 3'-untranslated-region sequences. In addition, four different Gogo-DQA1 alleles belonging to three different allelic lineages were detected. The Mhc-DRB-DQA1 haplotypes of these gorillas were deduced based on the obtained Mhc-DRB and -DQA1 sequences and the two published Mhc-DRB haplotypes of the lowland gorilla Sylvia. All deduced Gogo-DRB-DQA1 haplotypes show gene constellations different from known HLA-DRB-DQA1 haplotypes, while some of the Gogo-DRB haplotypes presented here contain more DRB genes than the HLA-DRB haplotypes. Based on phylogenetic trees, bootstrap analyses, and the gorilla, chimpanzee, and human Mhc-DRB haplotypes described, we propose that at least two Mhc-DRB loci, here tentatively designated Mhc-DRBI and -DRBII, existed on an ancient primate Mhc-DRB haplotype. The Mhc-DRB1*01, -DRB1*02 (-DRB1*15 and -DRB1*16), -DRB1*03 (-DRB1*03, -DRB1*08, -DRB1*11, -DRB1*12, -DRB1*13, and DRB1*14), and -DRB1*10 allelic lineages and -DRB3 and -DRBY loci probably evolved from the hypothetical primate Mhc-DRBI locus, whereas the present primate Mhc-DRB2, -DRB4, and -DRB6 loci originate from the ancient Mhc-DRBII locus of this core primate Mhc-DRB haplotype.

Amino Acid Sequence↗

Major histocompatibility complex class II polymorphisms in humans and chimpanzees.

Allelic variation at the MhcPatr-DR and -DQ loci was studied by molecular biological techniques and compared to available HLA data. With regard to the number of allelic lineages, the chimpanzee shows a condensation of its major histocompatibility complex (MHC) class II repertoire as compared to humans. This does not have an impact on the overall degree of MHC class II polymorphism in the chimpanzee since a few lineages that are oligomorphic in humans display an extensive degree of polymorphism in the chimpanzee.

Alleles↗

Mhc-DQB repertoire variation in hominoid and Old World primate species.

Comparison of 87 distinct Mhc-DQB sequences, obtained from 13 primate species, demonstrates that five out of eight trans-species Mhc-DQB allele lineages are at least 30 million years old and predate divergence of hominoid and Old World primate species. One lineage may be much older because its members are not only traced back in higher primates, but also are present in a New World primate species. Comparing Mhc-DQB repertoire variation in distinct species, allows one to pinpoint when certain polymorphisms were lost or gained in primate evolution. Heterogeneity observed among members of trans-species Mhc-DQB allele lineages can be explained in major part by point mutations, whereas intraexonic crossing-over is a potent mechanism in generating new allele lineages. The stability of Mhc-DQB polymorphisms is influenced by selective forces because distinct allele lineages appear to have accumulated nucleotide substitutions and amino acid replacements at different rates.

Alleles↗

Evolutionary relationships among the primate Mhc-DQA1 and DQA2 alleles.

The variation of the Mhc-DQA1 and DQA2 loci of ten different primate species (hominoids and Old World monkeys) was studied in order to obtain an insight in the processes that generate polymorphism of major histocompatibility complex (Mhc) class II genes and to establish the evolutionary relationships of their alleles. To that end nucleotide sequences of 36 Mhc class II DQA1 and seven DQA2 second exons were determined and phylogenetic trees that illustrate their evolutionary relationships were constructed. We demonstrate the existence of four primate Mhc-DQA1 allele lineages, two of which probably existed before the separation of the ancestors of the hominoids and Old World monkeys (approximately 22-28 million years ago). Mhc-DQA2 sequences were found only in the hominoid species and showed little diversity. We found no evidence for a major contribution of recombinational events to the generation of allelic diversity of the primate Mhc-DQA1 locus. Instead, our data suggest that the primate Mhc-DQA1 and DQA2 loci are relatively stable entities that mutated primarily as a result of point mutations.

Alleles↗

Mhc-DRB diversity of the chimpanzee (Pan troglodytes).

Fifty-four chimpanzee Patr-DRB and five human HLA-DRB second exons were cloned and sequenced from thirty-five chimpanzees and four human B-cell lines and compared with known Mhc-DRB sequences of these two species. Equivalents of the HLA-DRB1*02, -DRB1*03, -DRB1*07 allelic lineages and the HLA-DRB3, -DRB4, -DRB5, -DRB6, and -DRB7 loci were all found in the chimpanzee. In addition, two chimpanzee Patr-DRB lineages (Patr-DRBX and -DRBY) were found for which no human counterparts have been described. None of the Patr-DRB sequences is identical to known HLA-DRB sequences. The Patr-DRB1*0702 and HLA-DRB1*0701 alleles are the most similar sequences in a comparison between the two species and differ by only two nucleotides out of 246 sequenced. Equivalents of the HLA-DRB1*01, -DRB1*04, and -DRB1*09 alleles were not found in our sample of chimpanzees. A per locus comparison of the number of Patr-DRB alleles with the HLA-DRB alleles shows that the Patr-DRB3, -DRB4, -DRB5, and -DRB6 locus are, thus far, more polymorphic than their human homologs. The polymorphism of the Patr-DRB1 locus seems to be less extensive than that reported for the HLA-DRB1 locus. Nevertheless, the Patr-DRB1 locus seems to be the most polymorphic of the Patr-DRB loci. Phylogenetic analyses indicate that the HLA-DRB1*09 allele may have originated from a recombination between a Mhc-DRB5 allele and the DRB1 allele of a Mhc-DR7 haplotype. Although recombination seems to increase the diversity of the Patr-DRB alleles, its contribution to the generation of Patr-DRB variation is probably low. Hence, most Patr-DRB diversity presumably accumulated via recurrent point mutations. Finally, two distinct Patr-DRB haplotypes are deduced, one of which (the chimpanzee equivalent of the HLA-DR7 haplotype) is probably older than 6-8 million years.

Amino Acid Sequence↗

A personal computer program for large-scale comparisons of related nucleotide sequences.

A personal computer program (COMPSEQ) has been developed which can present an informative listing of pre-aligned exonic nucleotide sequences and of their translations to amino acid sequences as well run triplet-oriented analyses on these sequences in a given reading frame. The sequence listing focuses on the differences between related sequences by suppressing the concordances between them.

Algorithms↗

Diversity of immunoglobulin heavy chain gene segment rearrangement in B lymphoblastoid cell lines from X-linked agammaglobulinemia patients.

X-linked agammaglobulinemia (XLA) is characterized by an arrest in early B lymphocyte differentiation. Precursor B cells are present in the bone marrow (BM), whereas peripheral blood B cell numbers are severely decreased. A series of Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines (BLCL) was established from peripheral blood of three XLA patients belonging to one pedigree. These BLCL manifested productive VHDJH rearrangements and a random utilization of the VH families. The CDR3 regions of the rearrangements varied in length from 12 to 47 nucleotides and included N regions in all cases. The results supported the conclusion that the few B lymphocytes in peripheral blood of XLA patients exhibit all mechanisms that generate immunoglobulin (Ig) heavy (H) chain diversity. However, no evidence for somatic mutation was found. Within the VH3 family 50% of the expressed VH gene segments belonged to a single subgroup and within the VH4 family a preferential utilization of one VH4 gene element was observed. The utilization of H chain joining (HH) elements was biased to JH4 and JH6 and a high percentage of the CDR3 regions was found to be generated by unconventional mechanisms, such as multiple D usage and the fusion of D elements to D segments with irregular recombination recognition signals. These unique features of the recombined and expressed VHDJH regions in XLA may explain the inability of XLA patients to respond to a variety of antigens. Alternatively, they could be secondary to a B lymphocyte maturation defect in XLA.

Agammaglobulinemia↗

RFLP analysis of the HLA-, ChLA-, and RhLA-DQ alpha chain gene regions: conservation of restriction sites during evolution.

Genomic DNA samples, derived from a panel of 60 chimpanzees and 45 rhesus monkeys, were digested with the restriction enzymes Taq I and Bgl II and hybridized with an HLA-DQ alpha chain cDNA probe. The results were compared with the data available on a human reference panel. Use of the restriction enzyme Taq I and the DQ alpha chain probe allows the detection of five HLA-DQA1 and two HLA-DQA2 gene-associated fragments within the human population. For the ChLA and RhLA systems, 3 and 7 different DQA1-associated restriction patterns were detected, respectively, while for the chimpanzee a nonpolymorphic DQA2 (DX alpha) gene-associated fragment was also observed. The equivalent of the HLA- and ChLA-DQA2 genes appears to be absent in the rhesus monkey. The ChLA-DQA1 and -DQA2 gene-associated RFLP patterns are identical in man and chimpanzee, whereas such restriction site conservation is not seen in the rhesus monkey. The conclusion drawn is that the genetic organization of the HLA-DQA and ChLA-DQA gene regions, and possibly some of their allelic variabilities, already existed before man and chimpanzee separated in evolution. Moreover, the particular duplication which led to the generation of the HLA- and ChLA-DQA2 genes must have happened before speciation of members belonging to the superfamily Hominoidea (man, chimpanzee, etc), but probably after the separation of superfamily Cercopitecoidea (rhesus monkeys, baboons, etc.) from Hominoidea.

Animals↗