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Lipid rafts and pseudotyping
W F Pickl1, F X Pimentel-Muiños, B Seed
1Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Abstract:
Specific interactions between envelope and core proteins govern the membrane assembly of most enveloped viruses. Despite this, mixed infections lead to pseudotyping, the association of the viral cores of one virus with the envelopes of another. How does this occur? We show here that the detergent-insoluble lipid rafts of the plasma membrane function as a natural meeting point for the transmembrane and core components of a phylogenetically diverse collection of enveloped viruses. As a result, viral particles preferentially incorporate both the envelope components of other viruses as well as the extra- and intracellular constituents of host cell lipid rafts, including gangliosides, glycosyl phosphatidylinositol-anchored surface proteins, and intracellular signal transduction molecules. Pharmacological disruption of lipid rafts interferes with virus production.
Insights
Lipid rafts in cell membranes act as meeting points for viral components during mixed infections. This allows viruses to acquire envelopes from other viruses, influencing viral particle formation and production.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Enveloped virus assembly relies on interactions between viral envelope and core proteins.
- Pseudotyping, where viral cores associate with foreign envelopes, occurs during mixed infections.
- The mechanism behind pseudotyping and altered viral particle composition remains unclear.
Purpose of the Study:
- To investigate the role of lipid rafts in the membrane assembly of enveloped viruses.
- To understand how pseudotyping occurs at the molecular level during mixed viral infections.
- To identify host cell components involved in viral particle formation.
Main Methods:
- Analysis of viral protein and lipid raft interactions within the plasma membrane.
- Studying a phylogenetically diverse range of enveloped viruses.
- Utilizing pharmacological agents to disrupt lipid rafts and observe effects on virus production.
Main Results:
- Detergent-insoluble lipid rafts serve as a convergence point for viral envelope and core proteins.
- Viral particles incorporate host cell lipid raft components, including gangliosides and GPI-anchored proteins.
- Disruption of lipid rafts significantly impairs the production of infectious viral particles.
Conclusions:
- Lipid rafts are crucial platforms for enveloped virus assembly and facilitate pseudotyping.
- Viral particles acquire host cell lipid raft constituents, potentially altering their properties.
- Targeting lipid rafts offers a potential strategy for controlling viral propagation.