Structure of a Defective Provirus of Bovine Leukemia Virus

Ogawa, Yoshiaki; Sagata, Noriyuki; Tsuzuku-Kawamura, Junko; Koyama, Hiroyuki; Onuma, Misao; Izawa, Hisao; Ikawa, Yoji

doi:10.1111/j.1348-0421.1987.tb01333.x

Cited by 5 publications

(4 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Tax orf is the largest of the X region located between the env gene and the 3' LTR (Figure 2). The Tax protein is a target of the host immune response with T and B epitopes corresponding to regions 110–130/131–150 and 261–280, respectively [182]. …”

Section: The Blv Genomementioning

confidence: 99%

Mechanisms of leukemogenesis induced by bovine leukemia virus: prospects for novel anti-retroviral therapies in human

et al. 2007

View full text Add to dashboard Cite

In 1871, the observation of yellowish nodules in the enlarged spleen of a cow was considered to be the first reported case of bovine leukemia. The etiological agent of this lymphoproliferative disease, bovine leukemia virus (BLV), belongs to the deltaretrovirus genus which also includes the related human T-lymphotropic virus type 1 (HTLV-1). This review summarizes current knowledge of this viral system, which is important as a model for leukemogenesis. Recently, the BLV model has also cast light onto novel prospects for therapies of HTLV induced diseases, for which no satisfactory treatment exists so far.

show abstract

Section: The Blv Genomementioning

confidence: 99%

Mechanisms of leukemogenesis induced by bovine leukemia virus: prospects for novel anti-retroviral therapies in human

et al. 2007

View full text Add to dashboard Cite

show abstract

“…However, it is unknown how the expression of BLV is restricted in vivo to levels that are undetectable by conventional methods. Several candidate mechanisms for silencing have been proposed: (i) accumulation and export of unspliced viral mRNA by Rex protein (10), (ii) inactivation of a viral protein(s) caused by mutation or deletion of the proviral genome (29,36,48,49), (iii) blockage of the transcription of the viral LTR by DNA methylation (11,41), (iv) absence and/or inactivation of cellular factors that can activate LTR-directed transcription (2,24,28,39), and (v) induction and/or activation of cellular factors that repress the viral transcription (39,60). Recently, Van Den Broeke et al (49) reported that the occurrence of a deficient Tax protein as a result of mutation may play an important role in the silenced phenotype observed in BLV-induced ovine B-cell tumors.…”

Section: Discussionmentioning

confidence: 99%

The Region between Amino Acids 245 and 265 of the Bovine Leukemia Virus (BLV) Tax Protein Restricts Transactivation Not Only via the BLV Enhancer but Also via Other Retrovirus Enhancers

Tajima¹,

Aida²

2000

J Virol

View full text Add to dashboard Cite

Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis and is closely related to human T-cell leukemia virus type 1 (HTLV-1). The Tax protein of BLV acts through the 5 long terminal repeat (LTR)of BLV and activates the transcription of BLV. In this study, we amplified tax genes from BLV-infected cattle using PCR. We cloned the genes and monitored the transcriptional activities of the products. Seven independent mutant Tax proteins, with at least one amino acid substitution between residues 240 and 265, exhibited a markedly stronger ability to stimulate the viral LTR-directed transcription than the wild-type Tax Bovine leukemia virus (BLV) is the etiologic agent of enzootic bovine leukosis (EBL), which is the most common neoplastic disease of cattle, and it is often associated with persistent lymphocytosis, which is characterized by an increased number of normal B lymphocytes and the subsequent development of B-cell leukemia or lymphosarcoma after a long latency period (9). Sheep that are experimentally inoculated with BLV are readily infected, and some develop B-cell tumors at higher frequencies and after a shorter latency period than naturally inoculated cattle (3,15). BLV is closely related to human T-cell leukemia virus type 1 (HTLV-1), which is the causative agents of adult T-cell leukemia and a chronic neurological disorder known as tropical spastic paraparesis or HTLV-1-associated myelopathy (10). BLV and HTLV constitute a unique subgroup within the retrovirus family, being characterized by similar genomic organizations, similar strategies for gene expression, and similar pathologies. In addition to the structural proteins Gag, Pol, and Env, these viruses encode at least two regulatory proteins, namely, Tax and Rex, in the pX region located between the env gene and the 3Ј long terminal repeat (LTR). The Tax protein acts on a triplicate 21-bp motif known as the Tax-responsive element (TxRE) in the U3 region of the 5Ј LTR, and it stimulates transactivation of the virus genome (13,16,20,52). The TxRE consists of a cyclic AMP-response element (CRE)-like sequence, and it has been suggested that Tax binds indirectly to this element through cellular factors, such as members of the CREB/ATF family of basic-leucine zipper proteins which have been shown to bind to the CRE-like sequence (6, 43). The Tax protein of HTLV-1 is also known to modulate the expression of many cellular genes that are related to regulation of cell growth (61), but little is known about the Tax protein of BLV (27). The Tax proteins of BLV and HTLV-1 can cooperate with the Ha-Ras oncoprotein to induce the full transformation of primary rat embryo fibroblasts (34, 54). These findings indicate that the Tax protein is a key contributor to the oncogenic potential, as well as a key protein in the replication of the virus. The Rex protein interacts with the Rex-responsive element in the 3Ј R regions of the BLV and HTLV-1 mRNAs and enhances the cytoplasmic accumulation of singly spliced and unspliced transcripts. This enhancement lea...

show abstract

“…relation probably exists between clinical subtypes and the defective viruses (40,41). Likewise, defective proviruses have been found in BLV-induced lymphoid tumors and cell lines which have been established from leukemic cells of BLV-infected hosts with lymphosarcomas (16,23,32). Deletions were found in 1 of 9 (11.1%) (32) and in 4 of 17 (23.5%) (23) cases of EBL, and they involved sequences located mainly in the 5Ј half of the provirus as well as those in HTLV-1.…”

mentioning

confidence: 98%

Complete Bovine Leukemia Virus (BLV) Provirus Is Conserved in BLV-Infected Cattle throughout the Course of B-Cell Lymphosarcoma Development

Tajima

Ikawa

Aida

1998

J Virol

Self Cite

View full text Add to dashboard Cite

Bovine leukemia virus (BLV) and human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2) belong to the same subfamily of oncoviruses. Defective HTLV-1 proviral genomes have been found in more than half of all patients with adult T-cell leukemia examined. We have characterized the genomic structure of integrated BLV proviruses in peripheral blood lymphocytes and tumor tissue taken from animals with lymphomas at various stages. Genomic Southern hybridization with SacI, which generates two major fragments of BLV proviral DNA, yielded only bands that corresponded to a full-size provirus in all of 23 cattle at the lymphoma stage and in 7 BLV-infected but healthy cattle. Long PCR with primers located in long terminal repeats clearly demonstrated that almost the complete provirus was retained in all of 27 cattle with lymphomas and in 19 infected but healthy cattle. However, in addition to a PCR product that corresponded to a full-size provirus, a fragment shorter than that of the complete virus was produced in only one of the 27 animals with lymphomas. Moreover, when we performed conventional PCR with a variety of primers that spanned the entire BLV genome to detect even small defects, PCR products were produced that specifically covered the entire BLV genome in all of the 40 BLV-infected cattle tested. Therefore, it appears that at least one copy of the full-length BLV proviral genome was maintained in each animal throughout the course of the disease and, in addition, that either large or small deletions of proviral genomes may be very rare events in BLV-infected cattle.

show abstract

Structure of a Defective Provirus of Bovine Leukemia Virus

Cited by 5 publications

References 19 publications

Mechanisms of leukemogenesis induced by bovine leukemia virus: prospects for novel anti-retroviral therapies in human

Mechanisms of leukemogenesis induced by bovine leukemia virus: prospects for novel anti-retroviral therapies in human

The Region between Amino Acids 245 and 265 of the Bovine Leukemia Virus (BLV) Tax Protein Restricts Transactivation Not Only via the BLV Enhancer but Also via Other Retrovirus Enhancers

Complete Bovine Leukemia Virus (BLV) Provirus Is Conserved in BLV-Infected Cattle throughout the Course of B-Cell Lymphosarcoma Development

Contact Info

Product

Resources

About