How the DNA damage response determines the fate of HTLV-1 Tax-expressing cells.

National Fund for Scientific Research, Gembloux Agro-Bio Tech and Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liège, Belgium.
Retrovirology (Impact Factor: 5.66). 01/2012; 9:2. DOI: 10.1186/1742-4690-9-2
Source: PubMed

ABSTRACT How the Human T lymphotropic virus type 1 (HTLV-1) Tax protein stimulates proliferation while triggering cell cycle arrest and senescence remains puzzling. There is also a debate about the ability of Tax to activate or inhibit the DNA damage response. Here, we comment on these different activities and propose a conceptual rationale for the apparently conflicting observations.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A recent model proposing that a barrier is raised against tumor evolution in pre-cancer tissues is investigated. For that we quantify expression alterations in genome maintenance pathways: DNA damage response, death pathways and cell cycle and also differentially expressed genes in transcriptomes of pre-cancerous and cancerous lesions deposited in the GEO database. We find that the main alterations in pre-cancer samples comprising the barrier are: (1) DNA double strand-breaks signaling and repair pathways induction, (2) upregulation of cyclin-dependent kinases, (3) p53 dependent (and independent) repair and apoptosis pathways induction and (4) replicative senescence induction early in tissue transformation. In the cancer samples we find that the induced pathways in pre-cancer are systematically inhibited and the only remaining induced pathway is p53, whereas the retinoblastoma pathway arises induced in most samples. The results give support to the model, furthermore they reveal the involvement of additional mechanisms in pre-cancer, including the early induction of replicative senescence and of p53 independent apoptosis.
    Molecular BioSystems 09/2012; 8(11):3003-9. · 3.35 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Autophagy, a general homeostatic process for degradation of cytosolic proteins or organelles, has been reported to modulate the replication of many viruses. The role of autophagy in Human T-cell Leukemia Virus type 1 (HTLV-1) replication has, however, been uncharacterized. Here, we report that HTLV-1 infection increases the accumulation of autophagosomes and that this accumulation increases HTLV-1 production. We found that the HTLV-1 Tax protein increases cellular autophagosome accumulation by acting to block the fusion of autophagosomes to lysosomes, preventing the degradation of the former by the latter. Interestingly, the inhibition of cellular autophagosome-lysosome fusion using Bafilomycin A increased the stability of the Tax protein, suggesting that cellular degradation of Tax occurs in part through autophagy. Our current findings indicate that by interrupting the cell's autophagic process, Tax exerts a positive-feedback on its own stability.
    Journal of Virology 11/2012; · 5.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bovine leukemia virus (BLV) and human T-lymphotropic virus type 1 (HTLV-1) are closely related d-retroviruses that induce hematological diseases. HTLV-1 infects about 15 million people worldwide, mainly in subtropical areas. HTLV-1 induces a wide spectrum of diseases (e.g., HTLV-associated myelopathy/tropical spastic paraparesis) and leukemia/lymphoma (adult T-cell leukemia). Bovine leukemia virus is a major pathogen of cattle, causing important economic losses due to a reduction in production, export limitations and lymphoma-associated death. In the absence of satisfactory treatment for these diseases and besides the prevention of transmission, the best option to reduce the prevalence of d-retroviruses is vaccination. Here, we provide an overview of the different vaccination strategies in the BLV model and outline key parameters required for vaccine efficacy.
    Viruses. 01/2014; 6(6):2416-2427.


Available from