Mecanismos de oncogênese do human T-lymphotropic virus 1 (HTLV-1) na leucemia/linfoma de células T do adulto

Abstract

Cancer is the end result of a number of genetic changes that occur in the cell. These changes can alter the balance between the mechanisms of proliferation and programmed cell death (apoptosis), thereby promoting cell transformation. Infectious agents such as viruses, can induce the process of oncogenesis through the cell immortalization caused by viral gene expression. The Human T-lymphotropic virus 1 (HTLV-1) was the first human retrovirus described, associated with malignancy. This virus, which has tropism mainly by CD4+ T lymphocytes, promotes the activation and proliferation of infected cells, and cell transformation mediated by it presumably occurs through chronic T cell proliferation resulting in unregulated growth of infected cells and accumulation of genetic damage. Currently, it is known that the transformation of cells infected with HTLV-1 for leukemia / lymphoma, adult T-cell (ATLL) depends on several factors, among which the most important are the viral gene expression and the immune status of the host. Furthermore, it is known that prolonged expression of two viral proteins, Tax and HBZ, contributes to the development of this disease in infected individuals, since the permanent Tax induces proliferation of infected cells while HBZ inhibits viral expression and makes recognition immune. Recent studies have shown the important role of Tax oncoprotein in the development of ATLL through the activation of survival pathways, inhibition of checkpoints, mitigation of DNA repair mechanisms and the induction of expression of microRNAs with oncogenic potential in host cells. Although the majority of HTLV-1 individuals remain asymptomatic throughout life, there are those that exhibit neoplastic disease have a high mortality rate, with an average survival time of a few years. Given the wide distribution of viruses, including Brazil, it is found that a better understanding of the mechanisms of oncogenesis of HTLV-1 is necessary in order to provide new targets for the development of specific viral therapy, which may have impact in reducing the number of infected individuals, and hence the number of subjects with events ATLL.