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Acta Pharmacol Sin. 2017 Aug;38(8):1093-1103. doi: 10.1038/aps.2017.17. Epub 2017 Apr 10.

Human T-cell lymphotropic virus type 1 and its oncogenesis.

Author information

1
Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
2
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
3
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
4
University of Chinese Academy of Sciences, Beijing 100049, China.

Abstract

Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), a rapidly progressing clonal malignancy of CD4+ T lymphocytes. Exploring the host-HTLV-1 interactions and the molecular mechanisms underlying HTLV-1-mediated tumorigenesis is critical for developing efficient therapies against the viral infection and associated leukemia/lymphoma. It has been demonstrated to date that several HTLV-1 proteins play key roles in the cellular transformation and immortalization of infected T lymphocytes. Of note, the HTLV-1 oncoprotein Tax inhibits the innate IFN response through interaction with MAVS, STING and RIP1, causing the suppression of TBK1-mediated phosphorylation of IRF3/IRF7. The HTLV-1 protein HBZ disrupts genomic integrity and inhibits apoptosis and autophagy of the target cells. Furthermore, it is revealed that HBZ enhances the proliferation of ATL cells and facilitates evasion of the infected cells from immunosurveillance. These studies provide insights into the molecular mechanisms by which HTLV-1 mediates the formation of cancer as well as useful strategies for the development of new therapeutic interventions against ATL. In this article, we review the recent advances in the understanding of the pathogenesis, the underlying mechanisms, clinical diagnosis and treatment of the disease caused by HTLV-1 infection. In addition, we discuss the future direction for targeting HTLV-1-associated cancers and strategies against HTLV-1.

PMID:
28392570
PMCID:
PMC5547553
DOI:
10.1038/aps.2017.17
[Indexed for MEDLINE]
Free PMC Article

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