De Arcos-Jiménez Judith Carolina, González-Hernández Luz Alicia, Ratkovich-González Sarah, Sánchez-Reyes Karina, Alvarez-Zavala Monserrat, Ruiz-Briseño Mariana Del Rocio, Mosqueda-Gómez José Luis, Avila-Rios Santiago, Ramos-Solano Moises, Andrade-Villanueva Jaime Federico
Molecular Biology in Medicine PhD Program, CUCS, Universidad de Guadalajara, Guadalajara, Mexico.
HIV and Immunodeficiencies Research Institute, Clinical Medicine Department, CUCS, Universidad de Guadalajara, Guadalajara, Mexico.
Arch Virol. 2021 Jan;166(1):167-178. doi: 10.1007/s00705-020-04854-6. Epub 2020 Nov 1.
HIV infects its target cell and integrates into its genome as an essential step in its replication cycle. Proviral DNA is also subjected to the same transcriptional regulation as the host cell genome by its own transcriptional factors, with activating or repressive activity. There is a clear interaction between the presence of transcriptional repressors and a decrease in the rate of HIV replication, promoting gene silencing in infected cells, which serve as viral reservoirs. This represents a major obstacle for HIV eradication. The ZBTB gene family comprises 49 genes that encode transcription factors that have a repressor function in differentiation and development of cells of the lymphopoietic lineage, including the main target cells of HIV, CD4 T cells. In this cross-sectional study, we evaluated the expression profile of ZBTB genes in CD4 T cells of HIV-positive individuals with different levels of infection control. We found upregulation of gene expression of ZBTB4 (p < 0.01), ZBTB7B (p < 0.001), and ZBTB38 (p < 0.05) and downregulation of ZBTB16 (p < 0.01) in HIV-positive patients compared to HIV-negative individuals. Interestingly, in a deeper analysis, we observed that elite controllers had the highest levels of expression of the ZBTB38, ZBTB2, HIC1, ZBTB7A, ZBTB7B (ThPOK) and ZBTB4 genes, showing 2.56- to 7.60-fold upregulation compare to the ART-naïve group. These results suggest a possible contribution of these ZBTB transcriptional repressors in HIV-positive patients and a possible new molecular mechanism of viral control.
HIV感染其靶细胞并整合到其基因组中，这是其复制周期中的一个关键步骤。前病毒DNA也通过自身具有激活或抑制活性的转录因子，受到与宿主细胞基因组相同的转录调控。转录抑制因子的存在与HIV复制速率的降低之间存在明显的相互作用，促进了感染细胞中的基因沉默，而这些感染细胞充当了病毒库。这是根除HIV的一个主要障碍。ZBTB基因家族由49个基因组成，这些基因编码的转录因子在淋巴细胞谱系细胞（包括HIV的主要靶细胞CD4 T细胞）的分化和发育中具有抑制功能。在这项横断面研究中，我们评估了不同感染控制水平的HIV阳性个体的CD4 T细胞中ZBTB基因的表达谱。我们发现，与HIV阴性个体相比，HIV阳性患者中ZBTB4（p < 0.01）、ZBTB7B（p < 0.001）和ZBTB38（p < 0.05）的基因表达上调，而ZBTB16（p < 0.01）的基因表达下调。有趣的是，在更深入的分析中，我们观察到精英控制者中ZBTB38、ZBTB2、HIC1、ZBTB7A、ZBTB7B（ThPOK）和ZBTB4基因的表达水平最高，与未接受抗逆转录病毒治疗的组相比，上调了2.56至7.60倍。这些结果表明这些ZBTB转录抑制因子在HIV阳性患者中可能发挥作用，并且可能存在一种新的病毒控制分子机制。
