Zhu Huanzhang team AIDS is an infectious disease caused by human immunodeficiency virus (HIV) infection that seriously endangers people's lives and health
At present, the clinical treatment of AIDS is mainly antiretroviral therapy.
Although this therapy can inhibit the virus replication in the patient to the greatest extent, reduce the plasma viral load to a level that cannot be detected by the existing conventional testing methods.
However, once it is stopped With drug treatment, the viral load will rebound to the pre-treatment level
An important reason why AIDS cannot be cured is due to the long-term existence of a latent virus reservoir composed of HIV latent infected cells, and the molecular mechanism of how HIV-1 latent cells are formed and maintained has not yet been elucidated
Recently, the team of Professor Zhu Huanzhang of Fudan University published an online publication titled "FKBP3 induces human immunodeficiency virus-1 latency by recruiting histone deacetylase 1/2 to the viral long terminal repeat" (FKBP3 induces human immunodeficiency virus-1 latency by recruiting histone deacetylase 1/2 to the viral long terminal repeat" on the internationally renowned magazine mbio.
Enzyme 1/2 to the LTR region of the virus induces HIV-1 latent).
The newly identified important HIV-1 latent gene FKBP3 (or FKBP25) has been reported internationally, revealing that FKBP3 is involved in HIV through epigenetic modification.
It plays a key role in the establishment and maintenance of latency, and it has been confirmed that in the early stage of HIV-1 infection, T lymphocytes promote FKBP3 expression through interferon-gamma to inhibit HIV-1 infection
This study provides a new understanding of the mechanism of HIV latent infection and replication, and provides a potential drug intervention target for the functional treatment of AIDS
In this work, the researchers verified the potential candidate gene FKBP3 that is potentially related to HIV-1 on the basis of the large-scale CRISPR-Cas9 gene knockout screening, and found that multiple HIV-1 latently infected cell lines Knockout of FKBP3 in the latent model of CD4+ T lymphocytes and primary CD4+ T lymphocytes can promote latent HIV-1 transcriptional activation; at the same time, studies have found that FKBP3 can interact with YY1, HDAC1 and HDAC2 proteins, and can indirectly bind to HIV-1 through YY1 LTR region, and recruit HDAC1 and HDAC2 to HIV-1 LTR region, causing the level of histone acetylation near the HIV-1 integration site to decrease, leading to HIV-1 latent; the researchers also found that when HIV-1 infects cells The human body’s inherent innate immunity can increase the expression level of FKBP3 by secreting IFN-gamma, thereby inhibiting HIV-1 infection and replication, and inducing HIV-1 latency
In recent years, Zhu Huanzhang’s team has focused on the molecular mechanism of HIV latency and discovered that histone methyltransferases GLP, miRNA (miR-196b and miR-1290) and PEBP1 play an important role in the maintenance of HIV latency (EMBO).
Reports, 2020, 21 (11): e49305; Virology, 2013, 440, 182-189; Virology, 2015; 486: 228-38)
Professor Zhu Huanzhang’s team Dr.
Yang Xinyi is the first author of the paper, and Professor Zhu Huanzhang is the corresponding author
Relevant research has been funded by the National Infectious Disease Major Special Project, the National Natural Science Foundation of China NSFC-NIH Cooperation Project and the National Natural Science Foundation of China General Project
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