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Genetic polymorphisms in bovine leuk...
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Zhao, Xiangrong.
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Genetic polymorphisms in bovine leukemia virus genome: Transcriptional promoter, regulatory genes, and envelope structural gene.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Genetic polymorphisms in bovine leukemia virus genome: Transcriptional promoter, regulatory genes, and envelope structural gene./
作者:
Zhao, Xiangrong.
面頁冊數:
252 p.
附註:
Adviser: Gertrude Buehring.
Contained By:
Dissertation Abstracts International68-08B.
標題:
Biology, Bioinformatics. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3275673
ISBN:
9780549172505
Genetic polymorphisms in bovine leukemia virus genome: Transcriptional promoter, regulatory genes, and envelope structural gene.
Zhao, Xiangrong.
Genetic polymorphisms in bovine leukemia virus genome: Transcriptional promoter, regulatory genes, and envelope structural gene.
- 252 p.
Adviser: Gertrude Buehring.
Thesis (Ph.D.)--University of California, Berkeley, 2007.
Bovine leukemia virus (BLV) is an oncogenic virus widespread in cattle. It belongs to the genus Deltaretrovirus of the family Retroviridae along with human and simian T-lymphotropic viruses. The purpose of this dissertation research was to determine the natural variation among BLV isolates from different areas globally. Sequences related to transcription regulation (LTR and pXBL) were compared to a non-regulatory sequence (envelope gene [env]) for variability and selection pressures.
ISBN: 9780549172505Subjects--Topical Terms:
1018415
Biology, Bioinformatics.
Genetic polymorphisms in bovine leukemia virus genome: Transcriptional promoter, regulatory genes, and envelope structural gene.
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Bovine leukemia virus (BLV) is an oncogenic virus widespread in cattle. It belongs to the genus Deltaretrovirus of the family Retroviridae along with human and simian T-lymphotropic viruses. The purpose of this dissertation research was to determine the natural variation among BLV isolates from different areas globally. Sequences related to transcription regulation (LTR and pXBL) were compared to a non-regulatory sequence (envelope gene [env]) for variability and selection pressures.
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My first hypothesis was that the sequence of BLV LTR, especially its regulatory motifs, would be highly conserved, if their sequence integrity is critical to viral transcriptional regulation. With 52 viral isolates from cattle in 4 different continents, nucleotide variations from the consensus of all of the sequences were observed in most isolates and clustered phylogenetically, corresponding to the geographic distribution of donor cattle. Regulatory regions were significantly more conserved than non-regulatory regions in the BLV LTR overall, as well as in each LTR sub-regions (U3, R and U5). This indicates that selection occurs not only in coding sequences, but may also involve regulatory sequences. This was the first study to date (described in Chapter 2) on the natural diversity of the BLV LTR, and the first regarding possible selection pressures on regulatory sequences in deltaretroviruses.
520
$a
To further understand the BLV transcription and expression from a genetic point of view, from the 52 positive isolates described above, 30 non-redundant pXBL sequences (coding for regulatory proteins) were determined and then used for polymorphism and molecular evolutionary analyses. Rates of overall and synonymous substitutions were consistently lower, and nucleotide/amino acid composition bias and codon bias higher, in more-overlapped than in less-overlapped regions. Ratios of non-synonymous/synonymous substitutions were lowest in the tax, gene and its sub-regions. These data support the concept that a higher level of overlapping in coding regions correlates with greater evolutionary constraint. Tax, the most conserved among the four regulatory proteins, showed purifying selection consistent with its importance in the viral life cycle. This was the first study to date (described in Chapter 3) on polymorphisms in the full-length BLV pXBL coding region, and the first population study to examine triple-overlapping reading frames in any viral genome.
520
$a
As an enveloped retrovirus, BLV has envelope (Env) proteins, encoded by envelope structural gene (env), containing functional domains that determine viral infectivity and immunogenicity. Twenty-eight new env sequences were added to the current literature of 16 full-length BLV env gene sequences. The phylogenetic clustering, genotying, and geographic distribution of BLV env variations corresponded in most cases. Most natural variations are mapped to the surface of the proposed conformational models of BLV gp51 N-terminus and gp30 external domain, overlapping with or adjacent to immunogenetic epitopes. Analyses for evidence of possible selection pressures suggest the BLV env is under stringent negative selection overall, while strong positive selection is indicated for immunogenetic epitopes G. Those analyses expand available literature and provide information to help resolve certain controversial issues (e.g., relative variability in different BLV env sub-coding regions).
520
$a
As reported in Chapter 2, the Kamikawa cluster contains all and the only 6 isolates (UCD1326, JP-K1, K2, K3, K4, and K5) with a point mutation in the putative BLV GRE, G148A. This variation might be potentially detrimental to BLV glucocorticoid responsiveness, because it has only 6 nucleotides in common with the consensus mouse mammary tumor virus GRE, whereas the wild type putative BLV GRE has 7 in common. To further examine whether such a naturally existing, phylogenetic cluster-specific GRE variation is biologically significant, luciferase reporter assays in pTax-neo/pLuc-LTRv-hygro double-transfectant cell lines are in progress. The fifth chapter describes and discusses the materials and methods and preliminary data obtained to date, and predicted future results. (Abstract shortened by UMI.)
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