NS1-Truncated Recombinant Influenza Virus for Antiviral Immune Response
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Solution Overview
Problem
Existing vaccines and therapeutic agents for influenza and MERS-CoV viruses are inadequate in effectively preventing and treating various subtypes and strains, particularly mammalian adaptive avian influenza viruses and MERS-CoV, due to limitations in immune response induction and host immune system suppression.
Innovation Solution
A recombinant influenza virus is developed by fusing a gene encoding a furin cleavage site with an NS1 protein, incorporating foreign proteins like interferon-beta, to induce immune responses and block virus infections, using a nucleic acid and recombinant vector for protein expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing vaccines and therapeutic agents are used for influenza and MERS-CoV, then vaccination is performed, but immune response induction is insufficient and host immune system suppression occurs
Solution Approach 1:
The patent extracts and deletes the NS1 gene from the influenza virus genome, removing the component responsible for immune system suppression. This creates a recombinant virus lacking NS1 that can induce protective immune responses without suppressing the host immune system, directly resolving the contradiction between vaccine effectiveness and harmful immune suppression.
Solution Approach 2:
The patent converts the harmful NS1 protein into a beneficial component by fusing it with interferon-beta (IFN-β). The fused protein retains the ability to induce strong immune responses while the interferon-beta component provides antiviral activity. This transformation turns the previously harmful immune suppression mechanism into a beneficial immune activation system that protects against both influenza and MERS-CoV.
2Reliability
If NS1 protein is used in recombinant viruses, then antiviral activity is induced, but protein expression and function are compromised due to fusion with foreign genes
Solution Approach 1:
The patent segments the NS1 protein into two functional domains: the N-terminal region (residues 1-86) that maintains structural integrity and the C-terminal region that interacts with interferon-beta. This segmentation allows each domain to perform its specific function independently, ensuring both protein expression and antiviral activity are maintained despite the fusion with foreign genes.
Solution Approach 2:
The patent modifies the NS1 protein by deleting specific amino acid residues (residues 87-233) and fusing interferon-beta at a controlled position. This parameter change in the protein sequence enables the fusion protein to express correctly in host cells while maintaining the antiviral function, resolving the contradiction between protein expression and antiviral activity.
Data Source
AI summary
The present disclosure relates to a novel recombinant influenza virus, in which an interferon-beta gene, which is a foreign gene associated with an antiviral action, is introduced to an NS1 gene which is an influenza virus gene that is expressed first in the host to suppress the host immune system when infected with the influenza virus, and, in contrast to existing research, the interferon-beta is separated from the NS1 protein to carry out an intrinsic function of interferon-beta of inducing an antiviral action.