FKBP3 Induces Human Immunodeficiency Virus Type 1 Latency by Recruiting Histone Deacetylase 1/2 to the Viral Long Terminal Repeat.
FKBP3 Induces Human Immunodeficiency Virus Type 1 Latency by Recruiting Histone Deacetylase 1/2 to the Viral Long Terminal Repeat.
复制标题
FKBP3 通过将组蛋白脱乙酰酶 1/2 募集至病毒长末端重复序列来诱导人类免疫缺陷病毒 1 型潜伏期
作者：
Yang X;Zhao X;Zhu Y;Shen Y;Wang Y;Lu P;Jiang Z;Pan H;Yang J;Xun J;Zhao L;Wang J;Liang Z;Shen X;Liang Y;Lin Q;Liang H;Jin L;Zhang D;Liu J;Wang B;Jiang S;Xu J;Wu H;Lu H;Zhu H
由于潜伏的1型人类免疫缺陷病毒（HIV - 1）储存库的存在，HIV - 1无法被完全清除。然而，关于HIV - 1潜伏的相关事实，包括其建立和维持，尚不完整。由FKBP3基因编码的FKBP3属于亲免蛋白家族，参与免疫调节以及蛋白质折叠等细胞过程。在先前的一项研究中，我们通过CRISPR筛选发现FKBP3可能与HIV - 1潜伏有关。在本研究中，我们在多个潜伏感染的细胞系中敲除FKBP3基因以促进潜伏的HIV - 1激活。我们发现FKBP3可通过与YY1相互作用间接结合到HIV - 1长末端重复序列上，从而招募组蛋白去乙酰化酶1/2。这促进了组蛋白去乙酰化并诱导HIV - 1潜伏。最后，在原代潜伏细胞模型中，我们证实了FKBP3敲除对HIV - 1潜伏激活的作用。我们的研究结果提示了HIV - 1潜伏的表观遗传调控的一种新机制以及激活潜伏HIV - 1的一个新的潜在靶点。
The primary reason why AIDS cannot be completely cured is the existence of a latent HIV-1 reservoir. Currently, the facts of HIV-1 latency, including its establishment and maintenance, are incomplete. ABSTRACT Human immunodeficiency virus type 1 (HIV-1) cannot be completely eliminated because of existence of the latent HIV-1 reservoir. However, the facts of HIV-1 latency, including its establishment and maintenance, are incomplete. FKBP3, encoded by the FKBP3 gene, belongs to the immunophilin family of proteins and is involved in immunoregulation and such cellular processes as protein folding. In a previous study, we found that FKBP3 may be related to HIV-1 latency using CRISPR screening. In this study, we knocked out the FKBP3 gene in multiple latently infected cell lines to promote latent HIV-1 activation. We found that FKBP3 could indirectly bind to the HIV-1 long terminal repeat through interaction with YY1, thereby recruiting histone deacetylase 1/2 to it. This promotes histone deacetylation and induces HIV-1 latency. Finally, in a primary latent cell model, we confirmed the effect of FKBP3 knockout on the latent activation of HIV-1. Our results suggest a new mechanism for the epigenetic regulation of HIV-1 latency and a new potential target for activating latent HIV-1. IMPORTANCE The primary reason why AIDS cannot be completely cured is the existence of a latent HIV-1 reservoir. Currently, the facts of HIV-1 latency, including its establishment and maintenance, are incomplete. Using a CRISPR library in our earlier screening of genes related to HIV-1 latency, we identified FBKP3 as a candidate gene related to HIV-1 latency. Therefore, in this mechanistic study, we first confirmed the HIV-1 latency-promoting effect of FKBP3 and determined that FKBP3 promotes histone deacetylation by recruiting histone deacetylase 1/2 to the HIV-1 long terminal repeat. We also confirmed, for the first time, that FKBP3 can act as a transcription factor (TF) recruitment scaffold and participate in epigenetic regulation of HIV-1 latency. These findings suggest a new mechanism for the epigenetic regulation of HIV-1 latency and a new potential target for activating latent HIV-1.