The RNA-sensitive association between nucleolar NPM1/B23 and HTLV-I basic leucine zipper factor (HBZ) potentially acts on HBZ-induced cell transformation - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Frontiers in Microbiology Année : 2022

The RNA-sensitive association between nucleolar NPM1/B23 and HTLV-I basic leucine zipper factor (HBZ) potentially acts on HBZ-induced cell transformation

Résumé

Human T-cell leukemia virus type 1 is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia-lymphoma (ATL). The HTLV-1 basic leucine zipper factor (HBZ) has been associated to the cancer-inducing properties of this virus, although the exact mechanism is unknown. In this study, we identified (nucleophosmin) (NPM1/B23) as a new interaction partner of the major sHBZ isoform. We show that sHBZ and the less abundant uHBZ isoform interacts with nucleolar NPM1/B23 in infected cells and HTLV-1 positive patient cells, unlike equivalent antisense proteins of related non-leukemogenic HTLV-2,-3 and-4 viruses. We further demonstrate that sHBZ association to NPM1/B23 is sensitive to RNase. Interestingly, sHBZ was shown to interact with its own RNA. Through siRNA and overexpression experiments, we further provide evidence that NPM1/B23 acts negatively on viral gene expression with potential impact on cell transformation. These results suggest that the interaction of NPM1/B23 with sHBZ impact regulation of viral gene expression (including its own) and could contributes to the role of this viral protein in ATL development. Our results hence provide a new insight over HBZ-binding partners in relation to cellular localization and potential function on cell proliferation and should lead to a better understanding of the link between HBZ and ATL development. Contribution to the field Several DNA and RNA viruses are known to utilize different compartments of the cells for efficient replication related to viral proteins functions but also in diseases associated to infection. We have been studying the Human T-cell leukemia virus type 1 that is the causal agent of the aggressive adult T-cell leukemia-lymphoma (ATL). Herein, we showed for the first time that a protein named NPM1/B23 was more expressed in ATLL patients and that associated with the viral protein HBZ, which has been known to be crucial for ATL development. Through these results, we are those suggesting that this association between cellular and viral protein could represent a target to block the potential of infected patients to develop this virally induced form of leukemia. Such unique association could also be relevant in other forms of cancers either induced by other viruses or caused by mutations in cellular genes. More studies are currently underway in our laboratory to further explore the mechanism implicating this partnership.
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Dates et versions

hal-03923108 , version 1 (04-01-2023)

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Zhenlong Liu, Émilie Larocque, Yongli Xie, Yong Xiao, Guy Lemay, et al.. The RNA-sensitive association between nucleolar NPM1/B23 and HTLV-I basic leucine zipper factor (HBZ) potentially acts on HBZ-induced cell transformation. Frontiers in Microbiology, 2022, 13, ⟨10.3389/fmicb.2022.988944⟩. ⟨hal-03923108⟩
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