HCMV Virus Infectivity via LRP1 Inhibition and Cholesterol Modulation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current methods for producing infectious virus particles, such as human cytomegalovirus (HCMV), face limitations in yield due to the inhibitory effects of lipid addition during cell growth, necessitating improved methods for enhancing virus production and infectivity.

Innovation Solution

A method involving the use of compounds that decrease the activity of low-density lipoprotein-related receptor 1 (LRP1) and increase intracellular cholesterol levels to enhance the infectivity of HCMV virus particles, either by blocking LRP1 binding activity, reducing its surface expression, or modulating cholesterol import/export, thereby increasing the production of infectious virus particles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If lipids are added during cell growth, then cell membrane stability is improved, but virus production is inhibited

Engineering Contradiction:
Improvecell membrane stabilityVSAvoidvirus production
Core Design Contradiction:
Stability of the object's compositionVSProductivity

Solution Approach 1:

The patent applies preliminary action by adding lipids to the culture medium before virus infection occurs, during the cell growth phase. This timing allows the lipids to be incorporated into the cell membrane structure in advance, stabilizing it before the virus production phase begins, thereby avoiding the inhibitory effect of lipid addition during active virus replication

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the parameter of lipid concentration in the culture medium by optimizing the amount and type of lipids added during cell growth. By carefully controlling lipid parameters (concentration, timing, composition), the method achieves cell membrane stabilization without triggering the inhibitory effect on virus production that occurs when lipids are added during infection

Inventive Principle:
Principle #35Parameter changes

2Productivity

If de novo fatty acid synthesis is inhibited, then virus infectivity is reduced, but cell growth is improved

Engineering Contradiction:
Improvecell growthVSAvoidvirus infectivity
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent applies preliminary action by providing exogenous lipids to cells before virus infection, ensuring that cell membranes are pre-loaded with sufficient lipid content. This preliminary lipid supplementation allows the cells to maintain membrane integrity and function during virus production without relying on de novo fatty acid synthesis, which would otherwise be required for virus infectivity

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses exogenous lipids as an intermediary substance that mediates between cell growth requirements and virus infectivity needs. The added lipids serve as a substitute for de novo fatty acid synthesis, providing the necessary lipid components for virus particle assembly and infectivity without requiring the cell to actively synthesize fatty acids during infection

Inventive Principle:
Principle #24Intermediary (Mediator)

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 method significantly increases the infectivity of HCMV virus particles, as demonstrated by increased production of infectious progeny, improved viral antigen levels, and enhanced ability to initiate infection, providing a manufacturing advantage for vaccine production.

Implementation Method 1

contacting the cell with a compound that decreases activity of low density lipoprotein related receptor 1 (LRP1), wherein the virus particles produced in the cell in the presence of the compound display increased infectivity

Methodology Applied
Scientific EffectReceptor binding inhibition:

Implementation Method 2

contacting the cell with a compound that increases intracellular cholesterol, wherein the virus particles produced in the cell in the presence of the compound display increased infectivity

Methodology Applied
Scientific EffectCholesterol import modulation:

Data Source

PatentUS11008551B2Method to increase the infectivity of virus particles
Publication Date: 2021.05.18 THE TRUSTEES OF PRINCETON UNIV
  • US11008551B2 patent drawing
  • US11008551B2 patent drawing
  • US11008551B2 patent drawing

AI summary

A method for enhancing infectivity of HCMV virus particles is provided.