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Composition for activating latent HIV virus and application thereof

A technology of latent virus and composition, which is applied in the field of medicine, can solve the problems that have not been seen, increase the transcription and expression of latent HIV, and achieve the effect of long duration of effect and high induction and activation effect

Active Publication Date: 2019-04-16
WUHAN UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Prostratin and Bryostatin 1 are PKC activators. In vitro experiments have shown that they can significantly increase the transcription and expression of latent HIV, and the effect of the latter is better than that of the former. However, there are no related reports on animal experiments or clinical studies.

Method used

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  • Composition for activating latent HIV virus and application thereof
  • Composition for activating latent HIV virus and application thereof
  • Composition for activating latent HIV virus and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Schematic diagram of EcoHIV latent virus activation in embodiment 1 of the present invention

[0031] From the perspectives of T cell activation level, chromatin structure change and HIV-specific transcription factor activation, combined with a variety of latent infection activators (Latency-reversing agents, LRAs) synergistically activate viral transcription and protein expression. Low-dose αCD3 / αCD28 or α-CTLA 4 intraperitoneally promotes modest T cell activation in combination with HDACi (SAHA or VPA) and protein kinase C activator (Prostratin), or HDACi and protein kinase alone in the absence of T cell activation To activate the latent virus EcoHIV with agents, test the best activator combination, dose and maximum activation efficiency from the animal body level, cell level and molecular test.

Embodiment 2

[0032] Example 2 Schematic diagram of the structure of chimeric HIV constructed by the present invention

[0033]At present, in the research on "activation and killing" of latent HIV virus, most studies use latently infected primary cells and cell line models established in vitro by HIV-1, which have low physiological relevance and cannot completely replicate static HIV. The state of CD4+ T cells in the body, and more importantly, the lack of interaction with the immune system. At the same time, although the latent infection model established by using simian immunodeficiency virus (SIV) to infect non-human primates or HIV-1 to infect humanized mice provides valuable information, it is limited by the scarcity of animal sources. , high price, complicated operation and other factors, it is difficult to carry out large-scale application. In the present invention, the gp120 envelope protein in the NL4-3 strain is replaced by the envelope protein gp70 of murine leukemia virus, and ...

Embodiment 3

[0034] Embodiment 3 establishes the HIV infection animal model of various strain mice

[0035] The plasmid constructed in Example 2 was transformed into Stbl3 bacteria, a single clone was picked and inoculated in LB medium, and the plasmid was extracted for 293T cell transfection. The virus packaging steps are as follows:

[0036] 1) Take two centrifuge tubes filled with 16ml DMEM culture medium, add 300μg PEI to one tube, and add 100μg premixed vector plasmid to the other tube, vortex, and equilibrate at room temperature for 10 minutes.

[0037] 2) Take a 10ml pipette and blow up the medium mixed with PEI, add the medium mixed with the plasmid into the PEI drop by drop, and incubate at room temperature for 30 minutes.

[0038] 3) Take a T175 bottle, add 3ml of fetal bovine serum to it, add the carrier plasmid mixed with PEI into it, then pour the culture medium in the multilayer cell culture bottle into the T175 bottle, turn it upside down, left and right, and mix with the p...

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Abstract

The invention relates to the field of medicine, in particular to a composition for activating an HIV latent virus and application thereof. The composition consists of a monoclonal antibody drug, a histone deacetylase inhibitor and a PKC activator, wherein the monoclonal antibody drug is selected from an anti-human CD3 monoclonal antibody and an anti-human CD28 monoclonal antibody, the histone deacetylase inhibitor is selected from at least one of vorinostat and valproic acid, and a PKC activator is 12-deoxyphorbol-13-acetic acid (Prostratin). The main obstacle to cure the HIV is that the HIV establishes a hidden 'reservoir' of viruses in the body at the very early stage of infection. The composition has the effect of significantly activating latent HIV-infected CD4+ T cells, can activate the HIV latent virus simultaneously at the cellular level, the chromatin level and the HIV-specific transcription factor level, can fully activate the HIV pre-virus in the resting CD4+ T cells withoutsignificant cytotoxic side effects and is a necessary way to HIV functional healing.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a composition for activating HIV latent virus and its application. Background technique [0002] AIDS is an infectious disease that seriously threatens the safety of human life. At present, there is no effective vaccine and the existing drugs cannot completely cure it. With the continuous deepening of HIV research, it has been found that the main obstacle for HIV to be cured is that HIV has established a hidden virus "reservoir" (Latent reservoir) in the body at the very early stage of infection. AIDS treatment strategy - "activation and then kill" (Shock and Kill) is gradually becoming a hot spot in HIV research and has brought hope for a cure for HIV, known as the second revolution in HIV / AIDS treatment. At the same time, it cannot be ignored The reality is that with the progress of HIV infection, as the main effector cells in the body that can directly kill HIV-infected cells and secr...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61K45/06A61P31/18A61K31/16A61K31/19A61K31/222
CPCA61K31/16A61K31/19A61K31/222A61K39/39566A61K45/06A61K2039/505A61P31/18A61K2300/00
Inventor 顾潮江张同存于琪英
Owner WUHAN UNIV OF SCI & TECH
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