Mechanisms of HTLV-1 persistence and transformation

Boxus, Mathieu; Willems, Luc

doi:10.1038/sj.bjc.6605345

Cited by 114 publications

(106 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[6][7][8] In addition, Tax is thought to indirectly generate DNA damage by suppressing DNA repair processes and competing with cellular DNA damage response (DDR). 4,5 Recent data also support a direct role for Tax-induced reactive oxygen species in the occurrence of DNA lesions. 9 Conceptually, Tax activities are achieved through proteinprotein interactions in both nuclear and cytoplasmic cellular compartments.…”

mentioning

confidence: 89%

“…Tax indeed displays pleiotropic activities that cooperate to drive cell cycle progression and perturb genome stability. 4,5 For example, Tax shortens G 1 phase and accelerates transition into S phase by manipulating positive and negative G 1 phase regulators (ie, cyclin D/CDK complex, Rb and CDK inhibitors). [6][7][8] In addition, Tax is thought to indirectly generate DNA damage by suppressing DNA repair processes and competing with cellular DNA damage response (DDR).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Interaction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program

Boxus

Twizere

Legros

et al. 2012

Blood

View full text Add to dashboard Cite

The Tax oncoprotein encoded by the human T-cell leukemia virus type 1 plays a pivotal role in viral persistence and pathogenesis. Human T-cell leukemia virus type 1-infected cells proliferate faster than normal lymphocytes, expand through mitotic division, and accumulate genomic lesions. Here, we show that Tax associates with the minichromosome maintenance MCM2-7 helicase complex and localizes to origins of replication. Tax IntroductionHuman T-cell leukemia virus-1 (HTLV-1) is a retrovirus that infects approximately 20 million people worldwide. 1 Although the majority of infected people remain lifelong asymptomatic carriers, 2% to 5% develop either adult T-cell leukemia (ATL) or chronic inflammatory diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis. 1 Two major hallmarks of HTLV-1-infected cells are: preferential proliferation compared with normal lymphocytes 2 and tendency to accumulate genomic lesions, a prerequisite for oncogenesis. 3,4 Although the molecular mechanisms underlying T-cell transformation remain to be elucidated, it is generally accepted that the virally encoded Tax protein plays a central role. Tax indeed displays pleiotropic activities that cooperate to drive cell cycle progression and perturb genome stability. 4,5 For example, Tax shortens G 1 phase and accelerates transition into S phase by manipulating positive and negative G 1 phase regulators (ie, cyclin D/CDK complex, Rb and CDK inhibitors). [6][7][8] In addition, Tax is thought to indirectly generate DNA damage by suppressing DNA repair processes and competing with cellular DNA damage response (DDR). 4,5 Recent data also support a direct role for Tax-induced reactive oxygen species in the occurrence of DNA lesions. 9 Conceptually, Tax activities are achieved through proteinprotein interactions in both nuclear and cytoplasmic cellular compartments. 10 In the nucleus, Tax accumulates within foci called Tax speckled structures (TSS), 11 which overlap with the cellular machinery required for transcription, splicing, post-transcriptional modifications of proteins, DNA repair, and checkpoint control. 12 In this report, we further demonstrate that Tax recruits the MCM2-7 replicative helicase within the TSS and modulates the program of replication origin firing. Notably, this mechanism favors cell cycle progression and directly compromises genome stability. Methods Plasmids, antibodies, yeast 2-hybrid, and GST pulldownSee supplemental Methods (available on the Blood Web site; see the Supplemental Materials link at the top of the online article). Cell cultureHeLa, Rat-1, and 293GP2 cells were cultured in Dulbecco modified Eagle medium supplemented with 10% FBS and 2mM l-glutamine and penicillin/ streptomycin. Jurkat, HUT78 and JPX9 (Jurkat cell lines stably transfected either with tax-1 gene driven by a metallothionein-inducible promoter) were kept in RPMI 1640 supplemented with 10% FBS, 2mM l-glutamine, and penicillin/streptomycin. Expression of the viral protein was induced in JPX9 cells by adding 120 M zinc chloride...

show abstract

mentioning

confidence: 89%

mentioning

confidence: 99%

Interaction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program

Boxus

Twizere

Legros

et al. 2012

Blood

View full text Add to dashboard Cite

show abstract

“…Thus, HBZ modulates cellular signal pathways in addition to promoted proliferation. These findings indicate that HBZ is an essential viral gene for oncogenesis by HTLV-1 (Boxus and Willems 2009). Short hairpin RNA mediated knockdowns of HBZ expression in both ATL and HTLV-1 transformed cell lines reduce their proliferation.…”

Section: Role Of Hbz In Htlv-1-induced Oncogenesismentioning

confidence: 80%

“…In addition, HTLV-1 has a region at the 3' end of the virus, called pX, which encodes four partially overlapping reading frames (ORFs). These ORFs code for regulatory proteins which impact the expression and replication of the virus (Figure 1) (Boxus and Willems 2009). The viral RNA is reverse transcribed into double stranded DNA by the RT.…”

Section: Genomic Structure Of Htlv-1mentioning

confidence: 99%

“…Glucose transporter 1 (GLUT-1) is ubiquitously expressed cell surface receptor targeted by HTLV-1 (Manel et al 2003). Other cell surface receptors such as neuropilin 1 (NRP1) and surface heparan sulfate proteoglycans (HSPGs) have been reported to be target of HTLV-1 and are required for efficient entry (Boxus and Willems 2009). There is also evidence for cell-type specific receptors since a recent study has reported that HTLV-1 enters DCs by binding to the receptor DC-SIGN (Noula Shembade 2010.).…”

Section: Transmissionmentioning

confidence: 99%

See 1 more Smart Citation

Human T-Cell Lymphotropic Virus (HTLV-1) and Adult T-Cell Leukemia

Abbaszadegan¹,

Gholamin²

2011

T-Cell Leukemia

View full text Add to dashboard Cite

HTLV‐1

Bangham¹

2011

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Human T lymphotropic virus Type 1 (HTLV‐1) was the first human retrovirus discovered. Like the related virus human immunodeficiency virus Type‐1 (HIV‐1), HTLV‐1 persists lifelong in the host. HIV‐1 causes disease in over 99% of untreated infected people, whereas HTLV‐1 causes disease in only 2–8%: either a fatal leukaemia or lymphoma, or a disabling chronic inflammatory disease of the nervous system that causes paralysis of the legs. There is no satisfactory treatment for the malignant or inflammatory diseases, and no vaccine. HTLV‐1 is thought to have existed in the human population for over 50 thousand years; it is widely but unevenly distributed in the tropics and in some subtropical areas. A highly dynamic equilibrium is established in each infected person between persistent HTLV‐1 replication and the host immune response. The increasing understanding of this equilibrium has led to discoveries and conclusions of wide significance for virology, immunology and persistent infections. Key Concepts: Viral load and risk of HTLV‐1‐associated diseases are determined by the efficiency of the host's cell‐mediated immune response. Immunological efficiency is determined by host genetic polymorphisms – chiefly HLA – and by targeting critical weak points in the pathogen's life cycle. An immunodominant antigen is not necessarily the antigen recognised by the protective host immune response. Attributes of T cells such as phenotype, frequency and function do not correlate with their efficiency in protecting against a pathogen in a persistent infection at equilibrium. Viruses that target mobile cells such as leukocytes can use the mobility of the host cell to spread within and between hosts: they do not need to release large numbers of cell‐free virus particles. Some viruses, such as HTLV‐1, can spread from one cell to another by an active, triggered process that involves formation of a specialised cell‐to‐cell contact called a virological synapse.

show abstract

Mechanisms of HTLV-1 persistence and transformation

Cited by 114 publications

References 31 publications

Interaction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program

Interaction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program

Human T-Cell Lymphotropic Virus (HTLV-1) and Adult T-Cell Leukemia

HTLV‐1

Contact Info

Product

Resources

About