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

by | Jan 3, 2023 | Publications

Crit Rev Clin Lab Sci. 2023 Jan 2:1-23. doi: 10.1080/10408363.2022.2157791. Online ahead of print.


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.

PMID:36593730 | DOI:10.1080/10408363.2022.2157791

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