Phosphoinositide 3 kinase signalling may affect multiple steps during herpes simplex virus type-1 entry.

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Herpes simplex virus type-1 (HSV-1) interactions with host cells involve cytoskeletal rearrangements, including filopodia formation and membrane fusion.
• Understanding the molecular mechanisms governing viral entry is critical for developing antiviral strategies.

Purpose of the Study:

• To investigate the role of phosphoinositide 3 kinase (PI3K) signaling in HSV-1 entry and cell-to-cell fusion.
• To determine if PI3K inhibition affects viral entry independently of cell type and specific viral receptors.

Main Methods:

• Utilized a PI3K inhibitor (LY294002) to assess its effects on HSV-1 entry and HSV glycoprotein-mediated cell fusion.
• Employed immunofluorescence microscopy to analyze HSV-1-induced filopodia formation.
• Expressed a dominant-negative PI3K mutant to confirm the role of PI3K signaling.
• Investigated the impact of PI3K inhibition on RhoA activation.

Main Results:

• LY294002 significantly blocked HSV-1 entry in a cell-type- and gD receptor-independent manner.
• PI3K inhibition also reduced entry of other herpesviruses (β- and γ-herpesviruses) and affected HSV-1-induced filopodia formation.
• The inhibitor decreased HSV-1 glycoprotein-induced cell-to-cell fusion and expression of a dominant-negative PI3K mutant impaired both entry and fusion.
• PI3K signaling inhibition affected RhoA activation, which is necessary for HSV-1 entry into specific cell types.

Conclusions:

• Phosphoinositide 3 kinase (PI3K) signaling plays a multifaceted role in HSV-1 entry and fusion processes.
• Targeting PI3K signaling represents a potential broad-spectrum antiviral strategy against herpesviruses.