Application of benzamide compound in preparation of medicine for activating latent human immunodeficiency virus
A technology of HIV and benzamide, applied in the field of medicine, to achieve long-lasting, accelerated clearance, and high-efficiency effects
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Embodiment 1
[0041] Example 1: Chidamide activates the detection of latent HIV activity on the J-lat full length clone10.6 (abbreviated as J-lat10.6) cell model
[0042] In this example, the selected HIV latently infected cell model is the J-lat10.6 strain (Jordan A, Bisgrove D, Verdin E. HIV reproducibly establishes a latent infection after acute infection of T cells in vitro. EMBO J22:1868-1877, 2003). The J-lat10.6 strain cell is an A6 clone strain established after the HIV pseudovirus carrying the green fluorescent protein gene is infected with human T cells, and it is a commonly used HIV latently infected cell membrane in the world. The biological characteristic of this cell model is the integration of HIV pseudogenes, but the viral genes are not expressed (gene silencing). Since green fluorescent protein can be observed on living cells and detected by flow cytometry, green fluorescent protein is used as the reporter gene of this model, that is, as a marker of whether latently infect...
Embodiment 2
[0046] Example 2: Detection of chidamide activation of latent HIV activity on ACH-2 latently infected cell model (live HIV model)
[0047] In this example, the selected HIV latently infected cell model is the ACH-2 cell line (Folks TM, Clouse KA , Justement J, Rabson A, Duh E, Kehrl JH, Fauci AS. Tumor necrosis factor a induces expression of human immunodeficiency virus in a chronically infected T-cell clone. Proc Natl Acad Sci USA86:2365-2368, 1989.). The cells are derived from CEM cells and were first isolated from a 4-year-old Caucasian girl with acute lymphoblastic leukemia. Each ACH-2 cell is infected with a proviral HIV virus, which can express p24 in a low amount, and can be induced by TNF-α to express a large amount of HIV infectious virions. The system is a live HIV latent model, which can better simulate HIV latent cells in vivo. The sources of medicines used are as described in Implementation 1.
[0048] The relevant technical solutions are as follows: 1. Each we...
Embodiment 3
[0050] Example 3: Detection of chidamide activation of latent HIV activity on J1.1 latently infected cell model (live HIV model)
[0051] In this example, the selected HIV latently infected cell model is the J1.1 cell line (Perez VL, Rowe T , Justement JS, Butera ST, June CH, Folks TM. An HIV-1-infected T cell clone defective in IL-2production and Ca2+ mobilization after CD3stimulation. J Immunol 147:3145-3148, 1991.). From Jurkat cells, it is a cell line with latent HIV infection isolated from HIV-infected Jurkat cells. The system is also a living HIV latent model, which can better simulate HIV latent cells in vivo. The sources of drugs used are as described in Implementation 1.
[0052] The relevant technical solutions are as follows: 1. Each well contains 1*10 4 A 96-well plate was plated with J1.1 cells. 2. Chidamide, and control drugs SAHA, TSA, and Apcidin were incubated with the final concentrations shown in the figure to make the total volume of each well 0.2ml. 3...
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