Andrias davidianus ranavirus 1R encoding a delayed-early protein promotes cell proliferation by driving cell cycle...

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• Andrias davidianus ranavirus 1R (ADRV-1R) is a core gene in the Iridoviridae family, predicted to be a viral transcription factor (vTF).
• The specific functions and characteristics of ADRV-1R remain largely uncharacterized.

Purpose of the Study:

• To investigate the transcription, expression, and function of ADRV-1R in Chinese giant salamander thymus cells (GSTCs).
• To determine the role of ADRV-1R in viral replication, cell proliferation, and cell cycle progression.

Main Methods:

• Investigated ADRV-1R transcription and protein expression kinetics post-infection.
• Utilized cycloheximide (CHX) inhibition assay to classify ADRV-1R as a delayed-early gene.
• Performed subcellular localization studies.
• Analyzed the effects of ADRV-1R overexpression on GSTC proliferation and viral titer using flow cytometry and virus titration.

Main Results:

• ADRV-1R transcription initiated at 6 hours post-infection (hpi), with protein expression starting at 8 hpi.
• ADRV-1R is a delayed-early gene, localized in both the nucleus and cytoplasm.
• Overexpression of ADRV-1R significantly promoted GSTC proliferation by advancing cell cycle progression from G1 to S phase.
• ADRV-1R overexpression led to a 6.3-6.9-fold increase in ADRV titer in GSTCs by 36 hpi.

Conclusions:

• ADRV-1R functions as a delayed-early protein that enhances viral replication by promoting host cell proliferation and increasing viral titers.
• This study elucidates a novel mechanism by which ranaviruses manipulate host cell cycles for efficient propagation.