L233P mutation in the bovine leukemia virus Tax protein depresses endothelial cell recruitment and tumorigenesis in athymic nude mice

2019 ◽  
Vol 164 (5) ◽  
pp. 1343-1351 ◽  
Author(s):  
Hiroshi Mori ◽  
Takafumi Tomiyasu ◽  
Kanako Nishiyama ◽  
Maiko Matsumoto ◽  
Yoshiaki Osawa ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Nude Mice ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Cell Recruitment ◽  
Athymic Nude Mice ◽  
Tax Protein ◽  
Endothelial Cell Recruitment

scholarly journals Phosphorylation of bovine leukemia virus Tax protein is required for in vitro transformation but not for transactivation

Oncogene ◽  
1998 ◽  
Vol 16 (17) ◽  
pp. 2165-2176 ◽  
Author(s):  
Luc Willems ◽  
Cathy Grimonpont ◽  
Pierre Kerkhofs ◽  
Carine Capiau ◽  
Dirk Gheysen ◽  
...  
Keyword(s):  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
In Vitro Transformation ◽  
Tax Protein

scholarly journals Mutant Tax Protein from Bovine Leukemia Virus with Enhanced Ability To Activate the Expression of c-fos

2002 ◽  
Vol 76 (5) ◽  
pp. 2557-2562 ◽  
Author(s):  
Shigeru Tajima ◽  
Yoko Aida
Keyword(s):  
Bovine Leukemia Virus ◽  
Mutational Analysis ◽  
Leukemia Virus ◽  
Upstream Sequence ◽  
Wild Type ◽  
Cell Leukemia Virus Type ◽  
Mutant Proteins ◽  
Tax Protein ◽  
Human T Cell ◽  
Carg Box

ABSTRACT Bovine leukemia virus (BLV) is the etiologic agent of enzootic bovine leukosis. We previously identified several mutants of the BLV Tax protein with an ability to transactivate transcription via the BLV enhancer that is significantly greater than that of the wild-type Tax protein. Moreover, the mutant proteins also activated other viral enhancers, such as the enhancer of human T-cell leukemia virus type 1, which cannot be activated by wild-type BLV Tax. In this study, we demonstrated that the mutant proteins but not wild-type protein activate the upstream sequence of the human c-fos gene, which contains two major cis-acting elements, the CArG box and cyclic AMP-responsive element (CRE) motif. The mutant protein also strongly increased levels of endogenous c-fos mRNA in both human and bovine cell lines. On the other hand, the wild-type Tax protein has no activity to activate the expression of human c-fos, indicating that wild-type BLV Tax might discriminate between human and bovine c-fos promoter sequences. Deletion and point-mutational analysis of the cis-acting elements revealed that both the CArG box and the CRE motif were indispensable for the activation of c-fos by the mutant BLV Tax protein. Our results suggest that the mutant BLV Tax proteins might not only have the ability to enhance the production of virus particles but might also have increased ability to induce leukemia.

scholarly journals T-cell lymphoma induction by radiation leukemia virus in athymic nude mice.

1978 ◽  
Vol 148 (5) ◽  
pp. 1292-1310 ◽  
Author(s):  
P Ricciardi-Castagnoli ◽  
M Lieberman ◽  
O Finn ◽  
H S Kaplan
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Nude Mice ◽  
Leukemia Virus ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Target Cells ◽  
Transferase Activity ◽  
Athymic Nude Mice ◽  
Cell Markers

We report the development of extrathymic lymphoblastic lymphomas in RadLV-inoculated congenitally athymic nude mice. Thus, a leukemogenic virus which appears to require the presence of a thymus for its replication in normothymic mice can infect and transform target cells in the absence of this organ in the athymic host. The cells of one of these lymphomas have been established in vitro as a permanent cell line, BALB/Nu1. This cell line as well as a lymphoma induced in NIH/Swiss nude mice exhibit several T-cell markers, including terminal deoxynucleotidyl transferase activity, Thy-1.2, and Ly-2.2, but not Ly-1.2 nor TL. Ig determinants were not detected. The characteristics of the tumor cells support the view that cells with T-cell markers may normally exist in nude mice and undergo neoplastic transformation and clonal expansion after infection with a leukemogenic virus. The alternative possibility that virus-induced differentiation of prothymocytes may lead to the expression of Thy-1.2 and Ly-2.2 antigens is also considered. BALB/Nu1 cells release large numbers of type C viral particles. The virus, designated radiation leukemia virus (RadLV)/Nu1, has RTase activity and the protein profile characteristic of murine leukemia virus (MuLV). In radioimmunoassays, it cross-reacts completely with RadLV/VL3, a virus obtained from RadLV-induced C57BL/Ka thymic lymphoma cells in culture, and slightly with a xenotropic virus (BALB:virus-2) and with AKR MuLV. On inoculation into C57BL/Ka mice it has thymotropic and leukemogenic activity. In vitro it is B-tropic, poorly fibrotropic, and has limited xenotropic activity. Thus, RadLV/Nu1 appears to be biologically and serologically similar or identical to its parent virus, RadLV.

scholarly journals In Vivo Rescue of a Silent tax-Deficient Bovine Leukemia Virus from a Tumor-Derived Ovine B-Cell Line by Recombination with a Retrovirally Transduced Wild-Type taxGene

1999 ◽  
Vol 73 (2) ◽  
pp. 1054-1065 ◽  
Author(s):  
Anne Van Den Broeke ◽  
Claude Bagnis ◽  
Malgorzata Ciesiolka ◽  
Yvette Cleuter ◽  
Hans Gelderblom ◽  
...  
Keyword(s):  
Amino Acid ◽  
B Cell ◽  
Cell Line ◽  
Tumor Cells ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Wild Type ◽  
Consistent Finding ◽  
Tax Protein

ABSTRACT The lack of bovine leukemia virus (BLV) expression is a consistent finding in freshly isolated ovine tumor cells and in the B-cell lines derived from these tumors. In order to gain further insight into the mechanisms of BLV silencing in these tumors, we have used the YR2 B-cell line, which was derived from the leukemic cells of a BLV-infected sheep. This cell line contains a single, monoclonally integrated, silent provirus, which cannot be reactivated either by stimulation in vitro or by in vivo injection of the tumor cells or cloned proviral DNA in sheep. Sequence analysis of the taxgene from the YR2 cell line identified two G-to-A transitions (G7924 to A7924 and G8149 to A8149) that result in E-to-K amino acid changes at positions 228 and 303 in the Tax protein. Following retroviral vector-mediated transfer of a wild-type tax gene into YR2 cells, we showed that BLV mRNA, viral proteins, and virions were produced, demonstrating that the cellular factors required for virus expression were present in the original YR2 cell line. Injection of this transduced YR2 cell line in sheep led to the rescue of replication-competent BLV proviruses. The integrated competent proviruses exhibited unique chimeric tax genes, which arose from homologous recombination between the transduced wild-typetax and the YR2-derived tax sequences. Furthermore, in one of these functional recombinant proviruses, only the A8149-to-G8149 reversion was present, providing clear evidence that the defect underlying the silent phenotype in YR2 cells results from a single C-terminal E303-to-K303 amino acid substitution in the BLV Tax protein. Our observations suggest that a single strategically located mutation in tax provides a mechanism for BLV inactivation in B-cell tumors.

Rat embryo fibroblasts immortalization by bovine leukemia virus Tax protein

1995 ◽  
Vol 17 (2) ◽  
pp. 137-140 ◽  
Author(s):  
L. Willems ◽  
H. Heremans ◽  
A. Burny ◽  
R. Kettmann
Keyword(s):  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Rat Embryo ◽  
Tax Protein ◽  
Embryo Fibroblasts

L233P mutation of the Tax protein strongly correlated with leukemogenicity of bovine leukemia virus

2013 ◽  
Vol 167 (3-4) ◽  
pp. 364-371 ◽  
Author(s):  
Emi Inoue ◽  
Keiko Matsumura ◽  
Norihiko Soma ◽  
Shintaro Hirasawa ◽  
Mayuko Wakimoto ◽  
...  
Keyword(s):  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Strongly Correlated ◽  
Tax Protein

scholarly journals Analysis of Nucleotide Sequence of Tax, miRNA and LTR of Bovine Leukemia Virus in Cattle with Different Levels of Persistent Lymphocytosis in Russia

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 246
Author(s):  
Aneta Pluta ◽  
Natalia V. Blazhko ◽  
Charity Ngirande ◽  
Thomas Joris ◽  
Luc Willems ◽  
...  
Keyword(s):  
Bovine Leukemia Virus ◽  
Sequence Variation ◽  
Leukemia Virus ◽  
Lymphoproliferative Disease ◽  
P Value ◽  
Persistent Lymphocytosis ◽  
Tax Protein ◽  
Infected Cells ◽  
The Relationship ◽  
Bovine Species

Bovine Leukemia Virus (BLV) is the etiological agent of enzootic bovine leucosis (EBL), a lymphoproliferative disease of the bovine species. In BLV-infected cells, the long terminal repeat (LTR), the viral Tax protein and viral miRNAs promote viral and cell proliferation as well as tumorigenesis. Although their respective roles are decisive in BLV biology, little is known about the genetic sequence variation of these parts of the BLV genome and their impact on disease outcome. Therefore, the objective of this study was to assess the relationship between disease progression and sequence variation of the BLV Tax, miRNA and LTR regions in infected animals displaying either low or high levels of persistent lymphocytosis (PL). A statistically significant association was observed between the A(+187)C polymorphism in the downstream activator sequence (DAS) region in LTR (p-value = 0.00737) and high lymphocytosis. Our study also showed that the mutation A(−4)G in the CAP site occurred in 70% of isolates with low PL and was not found in the high PL group. Conversely, the mutations G(−133)A/C in CRE2 (46.7%), C(+160)T in DAS (30%) and A(310)del in BLV-mir-B4-5p, A(357)G in BLV-mir-B4-3p, A(462)G in BLV-mir-B5-5p, and GA(497–498)AG in BLV-mir-B5-3p (26.5%) were often seen in isolates with high PL and did not occur in the low PL group. In conclusion, we found several significant polymorphisms among BLV genomic sequences in Russia that would explain a progression towards higher or lower lymphoproliferation. The data presented in this article enabled the classification between two different genotypes; however, clear association between genotypes and the PL development was not found.

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