Dynamic Proteomics of Herpes Simplex Virus Infection

Area of Science:

• Virology
• Cell Biology
• Proteomics

Background:

• Viral infection studies typically focus on cell populations, overlooking individual cell variability.
• Understanding cell-to-cell differences is crucial for deciphering infection dynamics and outcomes.

Purpose of the Study:

• To investigate how cell-to-cell variability influences herpes simplex virus 1 (HSV-1) infection at the single-cell level.
• To identify host factors and cellular states that predict successful viral gene expression initiation.

Main Methods:

• Dynamic proteomics-imaging was employed to track 400 yellow fluorescent protein (YFP)-tagged host proteins in individual HSV-1 infected cells.
• Time-lapse fluorescence imaging quantified viral gene expression and host protein dynamics.

Main Results:

• Cell cycle position, motility, and local cell density predict the initiation of viral gene expression.
• Cell division significantly inhibits further viral gene expression (70% of dividing cells).
• Four host proteins (RFX7, geminin, SUMO2, RPAP3, SLTM, YTHDC1) were identified as modulated during infection, with SUMO2, RPAP3, SLTM, and YTHDC1 modulations dependent on ICP0 expression.

Conclusions:

• The success of HSV-1 infection is contingent on the host cell's state at the time of infection.
• Dynamic proteomics is a powerful tool for studying single-cell variations during viral infections.