HSV-1 virions engineered for specific binding to cell surface receptors.

Area of Science:

• Virology
• Molecular Biology
• Gene Therapy

Background:

• Displaying peptide epitopes on virion surfaces offers potential for viral studies and targeted gene therapy.
• Herpes Simplex Virus type 1 (HSV-1) is a versatile vector system.

Purpose of the Study:

• To engineer HSV-1 virions to display a modified glycoprotein C (gC) with a His-tag.
• To evaluate the binding and infectivity of these modified HSV-1 vectors.

Main Methods:

• Constructed an HSV-1 amplicon plasmid encoding a modified gC with a replaced heparan sulfate binding domain (His-tag).
• Generated HSV-1 virions using a helper virus system, resulting in amplicon vectors expressing modified gC.
• Utilized Western blot to confirm the presence of modified gC in purified virions.
• Assessed binding efficiency of His-tagged virions to cells expressing a pseudo-His-tag receptor compared to parental cells and wild-type virus.

Main Results:

• Western blot confirmed the presence of modified gC in purified HSV-1 virions.
• His-tagged HSV-1 virions demonstrated a four-fold increase in binding to cells with a pseudo-His-tag receptor compared to parental cells.
• Modified virions showed enhanced binding compared to wild-type HSV-1 to both cell types.
• Binding led to productive infections with reporter gene expression and cytopathic effects comparable to wild-type virions.

Conclusions:

• HSV-1 tropism can be manipulated to target non-herpes simplex virus binding receptors.
• Specific ligand-receptor interactions can enhance the infective capacity of HSV-1 vectors beyond wild-type levels.
• Engineered HSV-1 vectors show promise for targeted gene delivery and viral biology research.