Modified PRRS Virus Inducing Interferon via nsp1 Mutation

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Solution Overview

Problem

Current vaccines and medications for Porcine Reproductive and Respiratory Syndrome (PRRS) fail to induce a rapid and effective immune response, as they do not adequately stimulate the production of neutralizing antibodies and interferon, which are crucial for combating the virus.

Innovation Solution

A modified PRRS virus strain is developed that induces interferon type I production and secretion in infected cells, featuring mutations in the nsp1 protein gene, making it more sensitive to type I interferon and reducing its virulence, thereby serving as an effective vaccine or treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional PRRS vaccines are used, then the virus can be targeted for treatment, but the immune response is delayed and insufficient

Engineering Contradiction:

Improveimmune response effectivenessVSAvoidresponse time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent modifies the PRRS virus by deleting specific amino acids (R20P21R22) in the nsp1 protein, changing the viral parameters to enable interferon induction. This genetic modification alters the virus's interaction with host cells, transforming it from a virus that suppresses interferon to one that triggers interferon production, thereby resolving the contradiction between reliable immune response and rapid response time.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If PRRS virus infection occurs, then the virus can be detected in lymphoid organs for several months, but the host's immune response fails to clear the virus

Engineering Contradiction:

Improvevirus clearance capabilityVSAvoidviremia duration

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent converts the harmful effect of PRRS virus infection (which normally suppresses interferon and causes prolonged viremia) into a beneficial effect by using the virus itself to induce interferon production. The modified virus strain, lacking specific amino acids in nsp1, triggers the host's interferon response, which then clears the virus and eliminates prolonged viremia, transforming the virus's harmful persistence into a beneficial clearance mechanism.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Reliability

If PRRSV infection is used as a vaccine, then the virus can provide immunity, but the virus does not induce rapid production of neutralizing antibodies and interferon

Engineering Contradiction:

Improveprotective immunityVSAvoidinterferon production rate

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent modifies the virus's genetic parameters by deleting amino acids R20P21R22 in the nsp1 protein, which fundamentally changes the virus's ability to induce interferon. This parameter change transforms the virus from one that fails to produce interferon to one that rapidly induces interferon production, thereby resolving the contradiction between providing protective immunity and generating interferon at a rapid rate.

Inventive Principle:

Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The modified virus strain induces significant interferon production and increased sensitivity to type I interferon, leading to a reduced viral infectivity and attenuation, providing protection against PRRS in swine by stimulating both innate and specific immunity.

Implementation Method 1

A modified PRRS virus strain is developed that induces interferon type I production and secretion in infected cells

Methodology Applied

Scientific EffectInterferon production:

Implementation Method 2

featuring mutations in the nsp1 protein gene, making it more sensitive to type I interferon and reducing its virulence

Methodology Applied

Scientific EffectInterferon sensitivity:

Data Source

PatentUS9187731B2PRRS virus inducing type I interferon in susceptible cells

Publication Date: 2015.11.17 BOEHRINGER INGELHEIM VETMEDICA GMBH

AI summary

The present invention relates to the field of attenuated live viruses useful as vaccine or medicament for preventing or treating Porcine Reproductive and Respiratory Syndrome (PRRS) in swine, and is based on the surprising finding of a PRRS virus which is able to induce the interferon type I response of a cell infected by said virus. In one embodiment, the PRRS virus according to the invention is a PRRS virus mutant comprising, in comparison with the genome of a wild type strain, a mutation in the gene encoding the non structural protein 1 (nsp1) of said virus.