Ribosomal protein S25 promotes cell cycle entry for a productive BK polyomavirus infection

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• Viruses often employ non-canonical translation initiation due to limited coding capacity.
• Ribosomal protein S25 (eS25) is crucial for alternative translation initiation mechanisms like IRES.
• eS25 is not essential for cap-dependent translation, making its knockdown a tool to study viral reliance on non-canonical pathways.

Purpose of the Study:

• To investigate if BK polyomavirus (BKPyV) utilizes an Internal Ribosomal Entry Site (IRES) for translation.
• To determine the role of ribosomal protein S25 (eS25) in BKPyV replication.
• To explore the impact of eS25 on host cell cycle progression during viral infection.

Main Methods:

• BKPyV viral production was assessed in the presence and absence of eS25 via knockdown.
• Cell cycle analysis was performed on primary kidney cells with eS25 knockdown.
• Viral production timing relative to gene expression was examined.

Main Results:

• BKPyV robust viral production was dependent on eS25 prior to gene expression, not IRES-mediated translation.
• eS25 knockdown led to cell cycle arrest at G0/G1 and G2/M phases in primary kidney cells.
• The timing of BKPyV infection is influenced by the host cell's initial cell cycle state.

Conclusions:

• BKPyV replication relies on eS25 for an early step in its life cycle, distinct from IRES-dependent translation.
• eS25 plays a significant role in regulating host cell cycle progression.
• Host cell cycle status is a critical factor influencing BKPyV infection dynamics.