尽管 HIV-1 不感染 B 细胞，但感染人类免疫缺陷病毒 1 (HIV-1) 的患者 B 细胞淋巴瘤的发病率也会增加。 B 细胞淋巴瘤的发展似乎与 HIV-1 反式激活蛋白 (Tat) 的作用有关，该蛋白从 HIV 感染的细胞中释放并渗透到未感染的 B 细胞中，影响宿主细胞基因表达。慢性 HIV-1 感染后，Tat 会长时间作用于细胞，可能使细胞适应病毒蛋白的存在。这项工作的目的是确定和研究细胞对长期（慢性）暴露于 HIV-1 Tat 的适应机制。我们对在诱导型启动子或组成型启动子的作用下表达 Tat 的细胞进行了比较分析，使我们能够分别模拟急性和慢性 Tat 效应。我们发现 Tat 的急性作用导致细胞增殖受到抑制，这可能是由于与复制和蛋白质合成相关的基因下调所致。在 Tat 长期作用的情况下，细胞增殖得以恢复，与细胞保护（抗病毒）功能相关的基因表达增加。使用蛋白酶体抑制剂的分析表明，在长期作用的情况下，发生强烈的Tat蛋白水解，这可能是B细胞适应的主要机制。因此，B 细胞具有强大的机制来适应 HIV-1 Tat 的进入，其效率可能决定 HIV-1 感染患者淋巴瘤发生的频率。© 2024 作者。 《细胞生理学杂志》由 Wiley periodicals LLC 出版。

Patients infected with human immunodeficiency virus-1 (HIV-1) have an increased incidence of B-cell lymphoma, even though HIV-1 does not infect B cells. The development of B-cell lymphomas appears to be related to the action of the HIV-1 transactivator protein (Tat), which is released from HIV-infected cells and penetrates uninfected B cells, affecting host cell gene expression. Upon chronic HIV-1 infection, Tat acts on the cells for a long time, probably allowing the cells to adapt to the presence of the viral protein. The aim of this work was to identify and study the mechanism of adaptation of cells to prolonged (chronic) exposure to HIV-1 Tat. We performed a comparative analysis of cells expressing Tat under the action of either an inducible promoter or a constitutive promoter, allowing us to model acute and chronic Tat effects, respectively. We found that the acute action of Tat leads to the suppression of cell proliferation, probably due to the downregulation of genes associated with replication and protein synthesis. In the case of chronic action of Tat, cell proliferation was restored and the expression of genes associated with the implementation of protective (antiviral) functions of the cell was increased. Analysis using proteasome inhibitors showed that in the case of chronic action, intense Tat proteolysis occurred, which could be the main mechanism of B-cell adaptation. Thus, B cells have a powerful mechanism to adapt to the entry of HIV-1 Tat, the efficiency of which may determine the frequency of lymphomagenesis in HIV-1-infected patients.© 2024 The Author(s). Journal of Cellular Physiology published by Wiley Periodicals LLC.