Intra- and Inter-cellular Modeling of Dynamic Interaction between Zika Virus and Its Naturally Occurring Defective...

Area of Science:

• Virology
• Mathematical Biology
• Infectious Disease Dynamics

Background:

• Zika virus (ZIKV) infection poses a significant public health threat.
• Defective viral genomes (DVGs) are naturally occurring variants that can replicate in the presence of wild-type (WT) virus.
• DVGs have been proposed as a potential therapeutic strategy to reduce viral pathogenicity.

Purpose of the Study:

• To investigate the in silico infection dynamics and interactions between ZIKV WT and DVG genomes.
• To model the intracellular replication and virus production of ZIKV WT and DVG.
• To determine the key viral processes driving the interplay between ZIKV WT and DVG in different cell types.

Main Methods:

• Utilized ordinary differential equations (ODEs) to simulate ZIKV infection dynamics.
• Fitted simulation parameters to experimental data, including virus titers and assembled viral haplotypes.
• Analyzed data from Vero (mammalian) and C6/36 (mosquito) cell cultures across multiple virus passages.

Main Results:

• DVG production rates were generally higher in C6/36 cells compared to Vero cells.
• Simulations indicated a slower accumulation of infected cells when DVG-associated processes were highly activated.
• Identified key viral development processes that are faster in mosquito cells than in mammalian cells.

Conclusions:

• DVG replication dynamics differ significantly between mammalian and mosquito cells.
• DVGs may play a role in ZIKV attenuation by slowing infected cell accumulation.
• The findings support the potential of using engineered DVGs as a therapeutic strategy against ZIKV and other flaviviruses.