Multiplicity-dependent replication of varicella-zoster virus in interferon-treated cells

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Varicella-zoster virus (VZV) causes significant human disease.
• Interferon (IF) is a key antiviral cytokine.
• Understanding IF's efficacy against VZV is crucial for therapeutic strategies.

Purpose of the Study:

• To investigate the inhibitory effects of interferon (IF) on varicella-zoster virus (VZ) replication.
• To determine the influence of inoculum type (infected cells vs. cell-free virus) and multiplicity on IF efficacy.
• To assess the requirement for continuous IF presence for maximum antiviral activity.

Main Methods:

• Assaying VZV replication in human foreskin fibroblast (HFF) cultures using measures like infected cell yields, plaque formation, microfoci, and cytopathic effects.
• Challenging HFF cultures with varying multiplicities of VZV.
• Comparing the sensitivity of cell-free VZV and infected cell inocula to IF treatment.
• Evaluating the necessity of continuous IF presence in the culture medium.

Main Results:

• Higher interferon (IF) concentrations were required to inhibit VZV replication at high input multiplicities compared to low multiplicities.
• Preventing VZV-induced cytopathology necessitated even higher IF concentrations.
• Cell-free VZV was more sensitive to IF inhibition than VZV from infected cells.
• Continuous IF presence was essential for maximum antiviral effect against infected cell inocula, but not cell-free virus.

Conclusions:

• Interferon (IF) demonstrates inhibitory effects on varicella-zoster virus (VZ) replication in vitro.
• The efficacy of IF is influenced by VZV inoculum type and challenge multiplicity.
• Herpesviruses may establish infectivity reservoirs, posing a sustained challenge to IF-treated cells, potentially explaining variable IF responses.