Pathogenicity and virulence of human T lymphotropic virus type-1 (HTLV-1) in oncogenesis: adult T-cell leukemia/lymphoma (ATLL)

Abstract

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy of CD4⁺ T lymphocytes caused by human T lymphotropic virus type-1 (HTLV-1) infection. HTLV-1 was brought to the World Health Organization (WHO) and researchers to address its impact on global public health, oncogenicity, and deterioration of the host immune system toward autoimmunity. In a minority of the infected population (3–5%), it can induce inflammatory networks toward HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), or hijacking the infected CD4⁺ T lymphocytes into T regulatory subpopulation, stimulating anti-inflammatory signaling networks, and prompting ATLL development. This review critically discusses the complex signaling networks in ATLL pathogenesis during virus–host interactions for better interpretation of oncogenicity and introduces the main candidates in the pathogenesis of ATLL. At least two viral factors, HTLV-1 trans-activator protein (TAX) and HTLV-1 basic leucine zipper factor (HBZ), are implicated in ATLL manifestation, interacting with host responses and deregulating cell signaling in favor of infected cell survival and virus dissemination. Such molecules can be used as potential novel biomarkers for ATLL prognosis or targets for therapy. Moreover, the challenging aspects of HTLV-1 oncogenesis introduced in this review could open new venues for further studies on acute leukemia pathogenesis. These features can aid in the discovery of effective immunotherapies when reversing the gene expression profile toward appropriate immune responses gradually becomes attainable.

Keywords:

• Adult T-cell leukemia/lymphoma (ATLL)
• HTLV-1
• oncogenesis
• pathogenicity
• virus–host molecular interactions

Acknowledgements

We sincerely apologize to the authors whose prominent research could not be cited due to space constraints.

Author contributions

SAG, DJB, AM, and SAR: compiled the draft; DJB: proofread and revised the second revision; AM and SAR: designed the study, did the first revision and finalized the manuscript. All authors have read and approved the final manuscript.

Disclosure statement

The authors declare that they have no conflicts of interest regarding this manuscript.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.