FKBP3 Induces Human Immunodeficiency Virus Type 1 Latency by Recruiting Histone Deacetylase 1/2 to the Viral Long Terminal Repeat
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 fam...
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American Society for Microbiology
2021
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oai:doaj.org-article:a0946e0c9912490095a19784f1acaf6e2021-11-10T18:37:50ZFKBP3 Induces Human Immunodeficiency Virus Type 1 Latency by Recruiting Histone Deacetylase 1/2 to the Viral Long Terminal Repeat10.1128/mBio.00795-212150-7511https://doaj.org/article/a0946e0c9912490095a19784f1acaf6e2021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00795-21https://doaj.org/toc/2150-7511ABSTRACT 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.Xinyi YangXiaying ZhaoYuqi ZhuYinzhong ShenYanan WangPanpan LuZhengtao JiangHanyu PanJinlong YangJingna XunLin ZhaoJing WangZhiming LiangXiaoting ShenYue LiangQinru LinHuitong LiangLu JinDengji ZhangJun LiuBin WangShibo JiangJianqing XuHao WuHongzhou LuHuanzhang ZhuAmerican Society for MicrobiologyarticleHIV-1HIV-1 latencyFKBP3HDAC1/2acetylationMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021) |
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| collection |
DOAJ |
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| topic |
HIV-1 HIV-1 latency FKBP3 HDAC1/2 acetylation Microbiology QR1-502 |
| spellingShingle |
HIV-1 HIV-1 latency FKBP3 HDAC1/2 acetylation Microbiology QR1-502 Xinyi Yang Xiaying Zhao Yuqi Zhu Yinzhong Shen Yanan Wang Panpan Lu Zhengtao Jiang Hanyu Pan Jinlong Yang Jingna Xun Lin Zhao Jing Wang Zhiming Liang Xiaoting Shen Yue Liang Qinru Lin Huitong Liang Lu Jin Dengji Zhang Jun Liu Bin Wang Shibo Jiang Jianqing Xu Hao Wu Hongzhou Lu Huanzhang Zhu FKBP3 Induces Human Immunodeficiency Virus Type 1 Latency by Recruiting Histone Deacetylase 1/2 to the Viral Long Terminal Repeat |
| description |
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. |
| format |
article |
| author |
Xinyi Yang Xiaying Zhao Yuqi Zhu Yinzhong Shen Yanan Wang Panpan Lu Zhengtao Jiang Hanyu Pan Jinlong Yang Jingna Xun Lin Zhao Jing Wang Zhiming Liang Xiaoting Shen Yue Liang Qinru Lin Huitong Liang Lu Jin Dengji Zhang Jun Liu Bin Wang Shibo Jiang Jianqing Xu Hao Wu Hongzhou Lu Huanzhang Zhu |
| author_facet |
Xinyi Yang Xiaying Zhao Yuqi Zhu Yinzhong Shen Yanan Wang Panpan Lu Zhengtao Jiang Hanyu Pan Jinlong Yang Jingna Xun Lin Zhao Jing Wang Zhiming Liang Xiaoting Shen Yue Liang Qinru Lin Huitong Liang Lu Jin Dengji Zhang Jun Liu Bin Wang Shibo Jiang Jianqing Xu Hao Wu Hongzhou Lu Huanzhang Zhu |
| author_sort |
Xinyi Yang |
| title |
FKBP3 Induces Human Immunodeficiency Virus Type 1 Latency by Recruiting Histone Deacetylase 1/2 to the Viral Long Terminal Repeat |
| title_short |
FKBP3 Induces Human Immunodeficiency Virus Type 1 Latency by Recruiting Histone Deacetylase 1/2 to the Viral Long Terminal Repeat |
| title_full |
FKBP3 Induces Human Immunodeficiency Virus Type 1 Latency by Recruiting Histone Deacetylase 1/2 to the Viral Long Terminal Repeat |
| title_fullStr |
FKBP3 Induces Human Immunodeficiency Virus Type 1 Latency by Recruiting Histone Deacetylase 1/2 to the Viral Long Terminal Repeat |
| title_full_unstemmed |
FKBP3 Induces Human Immunodeficiency Virus Type 1 Latency by Recruiting Histone Deacetylase 1/2 to the Viral Long Terminal Repeat |
| title_sort |
fkbp3 induces human immunodeficiency virus type 1 latency by recruiting histone deacetylase 1/2 to the viral long terminal repeat |
| publisher |
American Society for Microbiology |
| publishDate |
2021 |
| url |
https://doaj.org/article/a0946e0c9912490095a19784f1acaf6e |
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