Transcriptional block of HTLV-I LTR by sequence-specific methylation

Saggioro, Daniela; Forino, M.; Chieco‐Bianchi, Luigi

doi:10.1016/0042-6822(91)90649-v

Cited by 32 publications

(27 citation statements)

References 28 publications

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“…In MT4 cells transformed with HTLV-1, which express a low level of viral RNA, the proviral genome is heavily methylated, and the treatment of such cells with 5-azacytidine, a demethylating agent, results in an increase in viral expression (30). In vitro methylation of the HTLV-1 LTR-chloramphenicol acetyltransferase construct or an LTR-luciferase construct resulted in significant inhibition of the transcription of the genes in transfected cells (3,31). These findings suggest that methylation of the proviral genome might serve to prevent viral expression.…”

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confidence: 73%

Latency of Viral Expression In Vivo Is Not Related to CpG Methylation in the U3 Region and Part of the R Region of the Long Terminal Repeat of Bovine Leukemia Virus

Tajima

Tsukamoto

Aida

2003

J Virol

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Bovine leukemia virus (BLV) is silent in most cells detectable in vivo, and the repression of its expression allows BLV to evade the host's immune response. In this study, we examined whether CpG methylation of DNA might be involved in the regulation of the expression of BLV in vivo. To investigate the effects of CpG methylation on the activity of the long terminal repeat (LTR) of BLV, we measured the transactivation activity of this region after treatment with the CpG methyltransferase SssI by using a luciferase reporter system. The activity of methylated LTR was significantly lower than that of nonmethylated LTR. Therefore, we examined the extent of CpG methylation of the U3 region and part of the R region of the LTR in BLV-infected cattle and in experimentally BLV-infected sheep at various clinical stages by the bisulfite genomic sequencing method. We detected no or minimal CpG methylation at all stages examined in cattle and sheep, and our results indicate that CpG methylation probably does not participate in the silencing of BLV in vivo.

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confidence: 73%

Latency of Viral Expression In Vivo Is Not Related to CpG Methylation in the U3 Region and Part of the R Region of the Long Terminal Repeat of Bovine Leukemia Virus

Tajima

Tsukamoto

Aida

2003

J Virol

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“…This, in turn, implies that Tax may modulate the DNA methylation through an interaction with HDAC1. In fact, in the HTLV-1-infected cells derived from ATL patients, which do not express the Tax protein, the viral LTR region is highly methylated (Saggioro et al, 1991). This hypermethylation of viral LTR is considered to be at least a cause of viral gene silencing and latent infection.…”

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confidence: 99%

The interaction of HTLV-1 Tax with HDAC1 negatively regulates the viral gene expression

2002

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Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are known to interact with several transcription factors and regulate their transcriptional activities. The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein activates transcription from its long terminal repeat (LTR) through interaction with cellular factors such as CREB and a transcriptional coactivator CBP/p300. However, little is known about the interaction between Tax and transcriptional repressors. Here, we demonstrate the physical and functional interaction between Tax and HDAC1. We found that HDAC1 represses the trans-activation function of Tax in 293T and MT4 cells. However, this repression was restored by treatment with an HDAC inhibitor, Trichostatin A. We also observed physical interaction between Tax and HDAC1 both in vitro and in vivo. The N-terminal region of HDAC1 (amino acid residues 28 -97) was required for this binding. Moreover, HDAC1 inhibited the synergistic trans-activation of Tax observed on ectopic expression of CBP. However, this repression was relieved by overexpression of CBP. Thus, HDAC1 is likely to compete with CBP in binding with Tax and functions as a negative regulator for the transcriptional activation by Tax.

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“…During retroviral infection, methylation is increased throughout the viral genome, particularly the viral long terminal repeats (LTR), suggesting that methylation can be a mechanism of suppression of viral expression and latency for human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1) (20,39,51,74,75). Previously, we showed that acute infection of cells with HIV-1 results in an increase in DNMT1 expression and activity, an overall increase in methylated genomic DNA in infected cells, and the de novo methylation of a single CpG dinucleotide in the gamma interferon (IFN-␥) gene promoter, which subsequently downregulated the expression of interferon (53).…”

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confidence: 99%

Infection of Lymphoid Cells by Integration-Defective Human Immunodeficiency Virus Type 1 Increases De Novo Methylation

Fang

Mikovits²,

Bagni

et al. 2001

J Virol

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DNA methylation, by regulating the transcription of genes, is a major modifier of the eukaryotic genome. DNA methyltransferases (DNMTs) are responsible for both maintenance and de novo methylation. We have reported that human immunodeficiency virus type 1 (HIV-1) infection increases DNMT1 expression and de novo methylation of genes such as the gamma interferon gene in CD4؉ cells. Here, we examined the mechanism(s) by which HIV-1 infection increases the cellular capacity to methylate genes. While the RNAs and proteins of all three DNMTs (1, 3a, and 3b) were detected in Hut 78 lymphoid cells, only the expression of DNMT1 was significantly increased 3 to 5 days postinfection. This increase was observed with either wild-type HIV-1 or an integrase (IN) mutant, which renders HIV replication defective, due to the inability of the provirus to integrate into the host genome. Unintegrated viral DNA is a common feature of many retroviral infections and is thought to play a role in pathogenesis. These results indicate another mechanism by which unintegrated viral DNA affects the host. In addition to the increase in overall genomic methylation, hypermethylation and reduced expression of the p16

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Transcriptional block of HTLV-I LTR by sequence-specific methylation

Cited by 32 publications

References 28 publications

Latency of Viral Expression In Vivo Is Not Related to CpG Methylation in the U3 Region and Part of the R Region of the Long Terminal Repeat of Bovine Leukemia Virus

Latency of Viral Expression In Vivo Is Not Related to CpG Methylation in the U3 Region and Part of the R Region of the Long Terminal Repeat of Bovine Leukemia Virus

The interaction of HTLV-1 Tax with HDAC1 negatively regulates the viral gene expression

Infection of Lymphoid Cells by Integration-Defective Human Immunodeficiency Virus Type 1 Increases De Novo Methylation

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