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Mutations in the bovine leukemia virus Tax protein can abrogate the long terminal repeat-directed transactivating activity without concomitant loss of transforming potential.

ABSTRACT: The bovine leukemia virus Tax protein transactivates gene expression directed by the viral long terminal repeat (LTR) and contributes to immortalization of primary cells. Theoretical analysis of the protein sequence revealed the presence of a putative zinc finger structure at its amino end. Selected mutations in that region completely abolished transactivation, demonstrating its importance for LTR-directed gene regulation. However, these mutations did not interfere with the ability of tax to bind zinc or to contribute to immortalization of primary cells. Thus, transactivation of bovine leukemia virus LTR and target cell transformation are independent functions of Tax and involve different functional domains of the protein.

SUBMITTER: Willems L

PROVIDER: S-EPMC525610 | biostudies-other | 1992 May

REPOSITORIES: biostudies-other

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Mutations in the bovine leukemia virus Tax protein can abrogate the long terminal repeat-directed transactivating activity without concomitant loss of transforming potential.

Willems L L Grimonpont C C Heremans H H Rebeyrotte N N Chen G G Portetelle D D Burny A A Kettmann R R

Proceedings of the National Academy of Sciences of the United States of America 19920501 9

The bovine leukemia virus Tax protein transactivates gene expression directed by the viral long terminal repeat (LTR) and contributes to immortalization of primary cells. Theoretical analysis of the protein sequence revealed the presence of a putative zinc finger structure at its amino end. Selected mutations in that region completely abolished transactivation, demonstrating its importance for LTR-directed gene regulation. However, these mutations did not interfere with the ability of tax to bin ...[more]

PMID: 1315045

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Project description:BACKGROUND:Limited data are available on the incidence of variations in nucleotide sequences of long terminal repeat (LTR) regions of Bovine Leukemia Virus (BLV). Consequently, the possible impact of SNPs on BLV LTR function are poorly elucidated. Thus, a detailed and representative study of full-length LTR sequences obtained from sixty-four BLV isolates from different geographical regions of Poland, Moldova, Croatia, Ukraine and Russia were analyzed for their genetic variability. METHODS:Overlap extension PCR, sequencing and Bayesian phylogenetic reconstruction of LTR sequences were performed. These analyses were followed by detailed sequence comparison, estimation of genetic heterogeneity and identification of transcription factor binding site (TFBS) modifications. RESULTS:Phylogenetic analysis of curated LTR sequences and those available in the GenBank database reflected the acknowledged env gene classification of BLV into 10 genotypes, and further clustered analysed sequences into three genotypes - G4, G7 and G8. Additional molecular studies revealed the presence of 97 point mutations distributed at 89 positions throughout all 64 LTR sequences. The highest rate of variability was noted in U3 and U5 subregions. However, the variability in regulatory sequences (VR) was assessed as lower than the variability within non-regulatory sequences (VNR) for both, U3 and U5 subregions. In contrast, VR value for R subregion, as well as for the total LTR, was higher than the VNR suggesting the existence of positive selection. Twelve unique SNPs for these LTR sequences localized in regulatory and non-regulatory elements were identified. The presence of different types of substitutions lead to the abrogation of present or to the creation of additional TFBS. CONCLUSION:This study represents the largest study of LTR genetic variability of BLV field isolates from Eastern part of Europe. Phylogenetic analysis of LTRs supports the clustering BLV variants based on their geographic origin. The SNP screening showed variations modifying LTR regulatory sequences, as well as altering TFBS. These features warrant further exploration as they could be related to proviral load and distinctive regulation of BLV transcription and replication.

Dataset Information

Mutations in the bovine leukemia virus Tax protein can abrogate the long terminal repeat-directed transactivating activity without concomitant loss of transforming potential.

Publications

Mutations in the bovine leukemia virus Tax protein can abrogate the long terminal repeat-directed transactivating activity without concomitant loss of transforming potential.

Similar Datasets

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