A new way to block HIV in mice
Figure 1: Screening of a potent HIV-1 repressor derived from a combination of ZFP362 fusion and repressor domain. Schematic of the design of the ZD3A construct leading to the ZD3A protein. NLS containing the ZFP362 domain can specifically bind to the HIV-1 LTR promoter and DNMT3A can recruit epigenetic silencing complexes. Binding of ZFP362-DNMT3A (ZD3A) can lead to long-term epigenetic transcriptional repression of LTR represented by methylated CpG DNA and suppressive histone methylation (right). b The effect of transfection of ZFP and ZD3A constructs on chronically infected Jurkat (CHI-Ju) cells was measured 3 days after treatment via RT-qPCR of Gag mRNA. Measurement of Gag mRNA from TNFα-activated CHI-Ju cells 3 days after transfection with cZD3A. The effect of transfection of construct ZFP and ZD3A on chronically infected Jarkat (CHI-Ju) cells 10 days after d-treatment was measured by RT-qPCR of Gag mRNA. e Here, KRAB (K), PWWP, ADD, methyltransferase (Mtase), catalytic domain of DNMT3A fusion (CD), and full-length DNMT3a (ZD3A) and control ZFP-362. f CHI-Ju cells were transfected with the fusion construct shown in (e), and RT-qPCR of Gag mRNA 10 days after transfection revealed that FC4 and FC10 were the most potent repressors of LTR activity. became. FC4 is hereafter referred to as ZPAMt after component ZFP362, PWWP, ADD, and Mtase domains, and FC10 is referred to as KMt after component ZFP362, KRAB, and Mtase domains. Western blotting of the g Myc tag confirmed the expression of ZPAMt, ZKMt, ZD3A, and ZFP. Representative Blots of n = 3 Biological Replication (h) LTR-driven GFP mRNA expression level data measured after overexpression of ZPAMt and ZKMt in microglial cell line HC69.5 are b–d, f, and b–d, and Expressed as the mean ± standard deviation (SD) of. NS. One-way ANOVA followed by Tukey’s multiple comparison post-test p-value. For b–d, f, and h, the error bars indicate the standard deviation of the sample processed three times, and the experiment was repeated twice. **** p ≤ 0.0001. The source data is provided as a source data file. Credit: DOI: 10.1038 / s41467-021-25839-2
Researchers at the City of Hope, a world-renowned research and treatment organization for cancer and diabetes, and Menzies Health Institute Queensland at Griffith University have developed a new anti-HIV protein that suppresses HIV levels in the bone marrow, spleen, and brain of mice. Did.According to a new study published in, the virus prevented the virus from replicating in these areas. Nature Communications..
Their research shows that scientists can manipulate nano-sized parts of cells called exosomes to carry therapeutic cargo to hard-to-reach places, including blood that is barely invading.brain barrier.This innovative delivery system paves the way for a future in which designed exosomes are thought to be able to carry cargo that suppresses either. Infection Or reconstruct the genetic material so that the pathogen is harmless.
“This innovative technology could be a viable way to provide treatment not only for HIV, but also for other diseases, including those that affect the brain, such as Alzheimer’s disease and Parkinson’s disease.” Said Professor Kevin Morris of the Gene Therapy Center in Hope. Griffith University Faculty of Pharmaceutical Sciences. Morris is a senior author of a new study.
The human immunodeficiency virus attacks cells that help the body fight infections, making individuals more vulnerable to other infections and diseases. Many researchers say that one way to treat HIV is disease In the process of blocking the virus’s ability to replicate and locking it into hibernation.
“The ZPAMt HIV protein repressor we developed is packaged in exosome nanoparticles that can invade cells and epigenetically silence HIV,” Morris said. “We show that these nanoparticles can” block and lock “the expression of HIV systemically. This is the first time that blocks and locks have been successfully provided to treat HIV in vivo in the brain. “
HIV can enter human body If in a dormant state; it can hide from the body’s immune system and avoid treatment. You can then reactivate it later. HIV, which is hidden in the brain, is especially difficult to treat because of the blood-brain barrier, which prevents both toxins and treatments from entering the brain.
Currently, there is no cure for HIV. Therefore, when someone becomes infected with HIV, that person will be infected with HIV for the rest of their lives. According to the US Centers for Disease Control and Prevention, an estimated 1.19 million people will be infected with HIV at the end of 2019 in the United States. According to the Australian Federation of AIDS Organizations, 29,045 people lived with HIV in 2019 in Australia.
Surya Shrivastava et al, exosome-mediated stable epigenetic suppression of HIV-1. Nature Communications (2021). DOI: 10.1038 / s41467-021-25839-2
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A new way to block HIV in mice
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