How does HTLV-1 cause adult T-cell leukaemia/lymphoma (ATL)?

Bangham, Charles R. M.; Ratner, Lee

doi:10.1016/j.coviro.2015.09.004

Cited by 79 publications

(62 citation statements)

References 86 publications

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“…HTLV-1 induced leukemogenesis in CD4+ T-cells is mediated by the expression of the viral oncoprotein Tax [6,16,23,[136][137][138][139][140]. Among its many oncogenic functions, Tax induces a potent inflammatory response through activation of the NF-kB pathway.…”

Section: Regulation Of the Expression Of Inducible Nitric Oxide Synthmentioning

confidence: 99%

“…Among its many oncogenic functions, Tax induces a potent inflammatory response through activation of the NF-kB pathway. Because Tax has an intermittent expression during the early stages of infection and it is rarely measureable during the acute phase of the disease, it is still not clear whether Tax exerts different functions between these two phases of virally-induced tumorigenesis [6,138,141]. In fact, Tax follows the approach of "hit and run", in which it promotes the oncogenic events during the infection course and it hides to prevent its elimination by the immune CTL response.…”

Section: Regulation Of the Expression Of Inducible Nitric Oxide Synthmentioning

confidence: 99%

“…As a result, breast milk allows contact between lymphoid cells which promotes cell to cell transmission of the virus, a more efficient manner of virus spread as compared to free particle infection [4,5]. Yet, for unknown reasons, only a few percent of infected individuals develop ATLL after a long period of latency [6]. Currently, there is no way to predict which infected patients will develop ATLL, and there is no effective treatment for those entering the acute phase of the disease.…”

Section: Introductionmentioning

confidence: 99%

“…The other infected cells either represent the latent reservoirs of the virus or lack properties to support the process of transformation [11][12][13][14]. Because HTLV-1 infection has evolved mechanisms that activate CD4+ T-cells and impair the immune CTL response, the outcome of the disease largely depends on two antagonist factors, the proviral load and the efficiency of the immune response against the infected cells [6,15]. Activation of proliferation and inhibition of tumor suppressors are also two major hallmarks of oncogenic events occurring during the long period of latent infection.…”

Section: Introductionmentioning

confidence: 99%

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Contribution of Inducible Nitric Oxide Synthase to the Transformation of HTLV-1 Infected CD4+ T-Cells

Baydoun¹,

Ratner²

2015

J Leuk

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The Human T-cell Leukemia Virus type 1 (HTLV-1), is the first retrovirus associated with a human cancer. HTLV-1 is the causative agent of an aggressive and fatal malignancy of CD4+ T lymphocytes known as Adult T-cell Leukemia lymphoma (ATLL). Since the discovery of the virus in 1980, intensive investigations have been undertaken to determine how HTLV-1 drives the transformation process in infected cells. This is because the oncogenic features of HTLV-1 make it an excellent tool to dissect the molecular pathways involved in cancer development. More important, HTLV-1 induced leukemia is a typical inflammation-mediated malignancy with constitutive activation of the NF-kB pathway, which is also a critical determinant in many other cancers. How NF-kB contributes to the leukemogenic process is not completely defined. We recently demonstrated that the NF-kB pathway induces the expression of inducible nitric oxide synthase (iNOS) in HTLV-1 induced leukemia. iNOS enzymatically generates nitric oxide, which is an oxidative and nitrosative agent of DNA and proteins. Nitric oxide was found to be associated with a large number of DNA Double Strand Breaks (DSBs) in HTLV-1 transformed cells. Here, we will review the major effects of nitric oxide on HTLV-1 induced leukemia.

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Section: Regulation Of the Expression Of Inducible Nitric Oxide Synthmentioning

confidence: 99%

Section: Regulation Of the Expression Of Inducible Nitric Oxide Synthmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Contribution of Inducible Nitric Oxide Synthase to the Transformation of HTLV-1 Infected CD4+ T-Cells

Baydoun¹,

Ratner²

2015

J Leuk

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“…HTLV-1 infection appears to represent the first event of a multistep oncogenic process. 2 After infection, the virus is integrated in the host genome and the viral transactivator protein Tax is expressed and interacts with many cellular pathways that regulate apoptosis, proliferation, and activation, and is involved in DNA repair and epigenetic regulation, resulting in oligoclonal expansions of HTLV-1-infected T cells. Although there is no hotspot of virus integration, experimental data suggest that integration may deregulate host genes involved in the pathophysiology of other leukemia/ lymphomas.…”

mentioning

confidence: 99%

ATL treatment: is it time to change?

Hermine¹

2015

Blood

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Safety of Retroviral Vectors in Clinical Applications: Lessons from Retroviral Biology and Pathogenesis

Neil

2017

Encyclopedia of Life Sciences

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The ability of retroviruses to integrate a precise copy of the viral genome into host cell DNA (deoxyribonucleic acid) has been harnessed in the development of retroviral vectors for stable delivery of foreign genes to target cells. Over several decades, these tools have been utilised in human medicine in diverse applications from cell lineage tracing by gene marking to correction of single‐gene disorders and therapy of cancer. The unanticipated occurrence of leukaemias due to vector insertional mutagenesis in trials of gene therapy led to an urgent search for safer vectors and delivery systems. The advent of T‐cell therapy for cancer has led to renewed interest in retroviral vectors as stable and efficient delivery vehicles and is supported by observations suggesting that mature T cells are relatively resistant to oncogenic transformation by retroviruses. However, this evidence is circumstantial and the long‐term risks are poorly understood. Retroviral vector safety is considered here from the perspective of the biology and pathogenesis of their parental viruses. It is suggested that robust cell suicide strategies to remove transduced cells are likely to be important if retroviral vectors are to be adopted widely for delivery of T‐cell therapy for cancer and other diseases. Key Concepts Retroviral vectors are useful tools for delivery of foreign genes to host cells in vitro and in vivo . The term retroviral vector is generally used for a vector based on a gamma‐retrovirus such as murine leukaemia virus. The term lentiviral vector is generally used for a vector based on human immunodeficiency virus type 1. Retroviral vectors have been tested in many clinical applications including cell lineage tracing, gene therapy and cancer therapy. Retroviruses can cause disease due to insertional mutagenesis or transduction of host cell genes. Retroviral and lentiviral integration are nonrandom processes that favour active regions of the genome, increasing the risks of insertional mutagenesis. Examples of retroviral transduction of host genes include a T‐cell receptor β‐chain gene, providing a parallel with cells engineered for use in T‐cell therapy of cancer.

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How does HTLV-1 cause adult T-cell leukaemia/lymphoma (ATL)?

Cited by 79 publications

References 86 publications

Contribution of Inducible Nitric Oxide Synthase to the Transformation of HTLV-1 Infected CD4+ T-Cells

Contribution of Inducible Nitric Oxide Synthase to the Transformation of HTLV-1 Infected CD4+ T-Cells

ATL treatment: is it time to change?

Safety of Retroviral Vectors in Clinical Applications: Lessons from Retroviral Biology and Pathogenesis

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