Herpes simplex virus 1 fluidizes the nucleus, enabling condensate formation.

Area of Science:

• Cellular Biophysics
• Virology
• Molecular Biology

Background:

• Cellular internal biophysical properties significantly impact molecular processes.
• Mechanisms controlling nuclear biophysical properties and their effects are poorly understood.
• Viruses may manipulate nuclear biophysics to enhance survival and replication.

Purpose of the Study:

• To investigate if viruses alter nuclear biophysical properties.
• To determine the role of herpes simplex virus 1 (HSV-1) in nuclear fluidity.
• To elucidate the function of HSV-1's infected cell protein 4 (ICP4) in viral replication.

Main Methods:

• Assessing changes in nuclear mesoscale fluidity induced by HSV-1 infection.
• Analyzing the effect of the HSV-1 ICP4 protein on nuclear fluidization.
• Investigating the impact of altered nuclear fluidity on viral replication compartment condensate formation and infectious virus production.

Main Results:

• HSV-1 infection increases the mesoscale fluidity of the nucleus.
• The HSV-1 protein ICP4 induces nuclear fluidization and supports synthetic nuclear condensate growth.
• Decreased nuclear fluidity inhibits viral condensate formation and reduces infectious HSV-1 production.

Conclusions:

• HSV-1 ICP4 enhances nuclear fluidity, facilitating condensate formation crucial for the viral life cycle.
• ICP4's function is likely to overcome nuclear crowding and confinement, barriers to virus replication.
• Modulating nuclear biophysical properties is a key viral strategy for replication.