Direct relationship between protein expression and progeny yield of herpes simplex virus 1

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• Viral protein expression and progeny virus yield vary significantly between individual cells.
• The direct relationship between viral protein expression levels and progeny virus production has not been previously quantified.

Purpose of the Study:

• To investigate the direct relationship between herpes simplex virus 1 (HSV-1) protein expression and progeny virus production.
• To determine if a threshold of viral protein expression is required for infectious virus production.

Main Methods:

• Constructed a reporter HSV-1 with Venus tagged to the late protein Us11.
• Separated infected cells into subpopulations based on Venus fluorescence (indicating L protein expression).
• Quantified virus yields and performed electron microscopy on each subpopulation.

Main Results:

• Infectious progeny virus production and nucleocapsid maturation were observed only when L protein expression surpassed a specific threshold.
• A direct, quantitative correlation was established between L protein expression levels and progeny virus yield.
• Nucleocapsid maturation was identified as a potential rate-limiting step in HSV-1 production.

Conclusions:

• HSV-1 progeny virus production is dependent on achieving a minimum threshold of L protein expression.
• This threshold suggests a critical regulatory step, potentially nucleocapsid maturation, controls the initiation of infectious virus production.