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New applications of Lpro protein and applications of FMDV L gene deletion mutant strain

A technology of protein mutants and proteins, applied in the field of virus immunology

Pending Publication Date: 2020-12-11
LANZHOU INST OF VETERINARY SCI CHINESE ACAD OF AGRI SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The role of viral proteins in innate immunity remains to be elucidated in order to control and eliminate these disease outbreaks and to better understand the interaction of viruses with the innate immune system

Method used

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  • New applications of Lpro protein and applications of FMDV L gene deletion mutant strain
  • New applications of Lpro protein and applications of FMDV L gene deletion mutant strain
  • New applications of Lpro protein and applications of FMDV L gene deletion mutant strain

Examples

Experimental program
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Embodiment

[0052] (1) Construction of the foot-and-mouth disease recombinant virus FMDV LbKO with Lb gene deletion

[0053] 1.1, the construction and rescue of the O-type foot-and-mouth disease recombinant virus of Lb gene deletion, comprise the following steps:

[0054] (1) primers are designed according to the sequence of prO-FMDV:

[0055] Primers for amplifying the L gene:

[0056] O1F: 5'-ATAGGTTTAATTAATGTTAAGCGTCTG-3' (SEQ ID NO: 2);

[0057] O1R: 5'-GTCTGTGGATCCCTCGTTGGAGCC-3' (SEQ ID NO: 3); the upstream primer O1F for amplifying the L gene contains a PacI restriction site, and the downstream primer O1R contains a BamHI restriction site.

[0058] Primers for deletion of the Lb gene on the L gene:

[0059] ODLbF: 5'-CACGCACCACAGGAAAAATGGGAGCCGGACAATCCAGTCC-3' (SEQ ID NO. 4);

[0060] ODLbR: 5'-GGACTGGATTGTCCGGCTCCCATTTTTCCTGTGGTGCGTG-3' (SEQ ID NO. 5);

[0061] (2) Using the plasmid prO-FMDV of the recombinant O-type foot-and-mouth disease virus rescue system as a template, u...

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Abstract

The present invention belongs to the field of virus immunology and particularly relates to new applications of Lpro protein and applications of an FMDV L gene deletion mutant strain. The present invention finds that the Lpro hinders JAK-STAT signal transduction in a dose-dependent manner. At the same time, a new function of the Lpro is discovered, i.e., intracellular components of a JAK-STAT pathway in cells are degraded in a lysosome-dependent manner through interaction with a specific region of STATs, rather than acting on the JAK-STAT signal transduction through classical protease activityof the Lpro. A protease activity center site of the Lpro of the FMDV is a key site participating in a lysosome degradation pathway. A protease activity center site of the Lpro is a key site of K48 ubiquitination of the Lpro. The new applications of the Lpro protein and the applications of the FMDV L gene deletion mutant strain provide new targets and theoretical supports for prevention and controland vaccine design of viruses of RNA viridae, such as viruses of foot-and-mouth diseases.

Description

technical field [0001] The invention belongs to the field of virus immunology, especially relates to L pro The application of protein in the preparation of JAK-STAT signal transduction inhibitor, and the protein L (comprising two kinds of shear mutants of Lab and Lb) of RNA virus family (Picornaviridae) foot-and-mouth disease virus (FMDV), EMCV virus and SAFV 51 Novel functions of cysteine ​​residues (protease active sites). Background technique [0002] Interferons (IFNs) are a group of secreted proteins, usually induced by pathogen-associated molecular patterns (PAMPs) activated by host pattern recognition receptors (PRRs), that play key roles in host antiviral innate and adaptive immunity. Interferon-based therapy has been successfully used in the clinical treatment of many viral infections, such as hepatitis B virus (HBV). To date, three types of IFNs have been identified to make up the entire IFN family, among which type I (IFNα / β) and type II IFN (IFN-γ) are regulate...

Claims

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Application Information

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IPC IPC(8): C07K14/085C07K14/09C12N15/41C12N15/42A61K39/125A61K39/135A61P31/14
CPCC07K14/005A61K39/12A61P31/14C12N2770/32122C12N2770/32222C12N2770/32134C12N2770/32234A61K2039/5254A61K2039/552
Inventor 郑海学马旭升罗志宽杨帆宋锐曾宗波莫希丁·乔杜里曹伟军刘永杰张克山田宏毛若箐刘湘涛
Owner LANZHOU INST OF VETERINARY SCI CHINESE ACAD OF AGRI SCI
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