CN-117398465-B - Application of TAB2 protein as rabies treatment target

Abstract

The application of TAB2 protein as rabies treating target belongs to the field of biomedicine technology. In order to research the influence of host protein on RABV replication, further research on RABV pathogenic molecular mechanism and search for new therapeutic targets and medicines of rabies, the invention utilizes methods such as fluorescence quantification, western Blotting and the like to research the influence of host protein TAB2 on RABV replication, and as a result, the instant knockout or stable knockout of TAB2 gene can inhibit the replication of rabies virus, and then TAB2 protein can be used as a new target for rabies therapy. In addition, the present invention also discovers that the domains of TAB2 interacting with RABV M and the TAB2 proteins promote RABV replication by activating the TAK1-p38/MAPK signaling pathway, and that p38 inhibitor Gossypetin and TAK1 inhibitor Takinib are potential drugs for the treatment of RABV infection.

Inventors

• WANG HUALEI
• SUN JINGXUAN
• ZHANG HAILI
• LI YUANYUAN
• HUANG PEI
• BAI YUJIE
• SONG YUMENG
• Liu Yongsai

Assignees

• 吉林大学

Dates

Publication Date

20260508

Application Date

20231020

Claims (2)

1. 1. The application of a substance capable of inhibiting the expression of a mouse-derived TAB2 protein in preparing a medicament for treating rabies is characterized in that the accession number of the mouse-derived TAB2 protein on NCBI is NP-001346463.1, the substance capable of inhibiting the expression of the mouse-derived TAB2 protein is a substance capable of knocking down the expression of the TAB2 protein, the substance capable of knocking down the expression of the TAB2 protein is TAB2 siRNA, the TAB2 siRNA is siRNA1 with a nucleotide sequence shown as SEQ ID NO.9 or siRNA2 with a nucleotide sequence shown as SEQ ID NO.10 or siRNA3 with a nucleotide sequence shown as SEQ ID NO.11 or a mixture of siRNA1, siRNA2 and siRNA3, and the rabies is rabies caused by rabies viruses of a RABV CVS11 strain or a RABV SRV9 strain.
2. 2. The application of a substance capable of inhibiting the expression of a mouse TAB2 protein in preparing a medicament for inhibiting rabies virus replication is characterized in that the accession number of the mouse TAB2 protein on NCBI is NP-001346463.1, the substance capable of inhibiting the expression of the mouse TAB2 protein knocks down the expression of the TAB2 protein, the substance capable of knocking down the expression of the TAB2 protein is a TAB2 siRNA, the TAB2 siRNA is an siRNA1 with a nucleotide sequence shown as SEQ ID NO.9 or an siRNA2 with a nucleotide sequence shown as SEQ ID NO.10 or an siRNA3 with a nucleotide sequence shown as SEQ ID NO.11 or a mixture of the siRNA1, the siRNA2 and the siRNA3, and the rabies virus is a RABV CVS11 strain or a RABV SRV9 strain.

Description

Application of TAB2 protein as rabies treatment target Technical Field The invention belongs to the technical field of biological medicine, and particularly relates to an application of TAB2 protein as a rabies treatment target. Background Rabies (Rabies) is an acute, highly fatal zoonotic infectious disease caused by rabies virus (Rabies virus, RABV) infection, and almost all warm-blooded animals can be infected. The disease has the characteristics of fast disease development and high disease death rate, and the disease livestock or patients often show clinical characteristics of mania, water terrorism, photophobia, dysphagia and the like, and once clinical symptoms appear, the disease death rate can reach 100%. According to World Health Organization (WHO) data, rabies is shown to be a single year in 150 countries over the world, with about 59000 people dying from the disease, about 95% of which occur in asia and africa. Therefore, from the perspective of virus-host interaction, the influence of host factors on RABV replication is researched, the regulation and control mechanism is deeply analyzed, novel therapeutic targets and therapeutic drugs are screened, the method has important significance for clinical treatment and comprehensive prevention and control of rabies, and theoretical support is provided for eliminating human rabies transmitted by dogs before 2030 worldwide. The RABV genome is a single-stranded, non-segmented negative-strand RNA of about 12kb in length, encoding 5 structural proteins, in order from 3 'to 5' ends, nucleoprotein (Nucleoprotein, N), phosphoprotein (Phosphoprotein, P), matrix protein (Matrixprotein, M), glycoprotein (Glycoprotein, G) and RNA-dependent RNA polymerase protein (RNA-DEPENDENT RNAPOLYMERASE, L). The RABVM protein is used as a multifunctional protein, and is involved in regulating and controlling the transcription and replication of viruses besides influencing the morphology, pathogenicity, assembly, budding and release of virus particles, and plays an important role in the replication process of RABV. TAB2 (TAK 1-binding protein 2) is a binding protein for transforming growth factor beta-activated kinase 1 (TAK 1), the total length of 693 aa, and the relative molecular mass is about 77kDa. TAB2 is often combined with TAB1, TAB3, and TAK1 to form a TAK1-TAB1-TAB2/3 complex, which exerts its biological functions by modulating the activity of the TAK1 protein. TAB2 is involved in regulating a variety of signal pathways including NF- κB, MAPK, etc. However, no report has been made as to whether TAB2 affects RABV replication. Rabies is an important zoonosis which damages global public health and affects the world economic development, and the pathogenic mechanism of the zoonosis is not clear at present, and an effective therapeutic drug is not available. Therefore, from the interaction angle of host protein and virus, research on the influence of host protein on RABV replication is of great significance to further research on the pathogenic molecular mechanism of RABV and search of new therapeutic targets and drugs. Disclosure of Invention In order to study the influence of host protein on RABV replication, further study RABV pathogenic molecular mechanism and find new therapeutic targets and medicines of rabies, the invention uses methods such as fluorescence quantification, western Blotting, direct immunofluorescence and the like to study the influence of host protein TAB2 on RABV replication from the aspect of interaction of host protein and virus, and provides theoretical basis for further study of RABV pathogenic molecular mechanism and finding new therapeutic targets and medicines. In order to solve the technical problems and realize the corresponding technical effects, the invention provides the following technical scheme: a first object of the present invention is to provide the use of a substance capable of inhibiting the expression of a mouse-derived TAB2 protein for the preparation of a product for the treatment of rabies, characterized in that said mouse-derived TAB2 protein has an accession number np_001346463.1 on NCBI. In one embodiment of the present invention, the agent capable of inhibiting expression of a murine TAB2 protein treats rabies by inhibiting the MAPK signaling pathway. In one embodiment of the invention, the rabies is a rabies caused by RABV CVS11 strain or RABV SRV9 strain. A second object of the present invention is to provide the use of a substance capable of inhibiting the expression of a murine TAB2 protein having the accession number np_001346463.1 on NCBI for the preparation of a product for inhibiting rabies virus replication. In one embodiment of the present invention, the agent capable of inhibiting expression of the murine TAB2 protein inhibits rabies virus replication by inhibiting the MAPK signaling pathway. In one embodiment of the invention, the rabies virus is RABV CVS11 strain or RABV SRV9 strain. In one embodiment of the