Human Papillomavirus Infectious Entry and Trafficking Is a Rapid Process

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Previous research suggested human papillomavirus (HPV) entry into host cells is a slow process, taking many hours.
• This perceived slowness conflicted with the rapid nature of intracellular transport pathways.
• A slow entry mechanism seemed incongruous with natural HPV infections in wounded epithelia.

Purpose of the Study:

• To investigate the actual speed of HPV intracellular trafficking and nuclear entry.
• To determine the influence of the cell cycle on the kinetics of HPV infection.
• To challenge the established notion of slow HPV nuclear import.

Main Methods:

• Utilized synchronized cell populations for precise timing of infection.
• Employed HPV16 pseudovirions (PsVs) containing reporter DNA.
• Monitored reporter gene expression and DNA localization at specific post-infection time points.

Main Results:

• Demonstrated rapid HPV trafficking, with detectable reporter gene expression by 8 hours post-infection in late S-early G₂/M phase cells.
• Visualized reporter DNA within the nucleus as early as 1-2 hours post-infection in cells infected just before mitosis.
• Identified mitosis as the primary rate-limiting step for nuclear entry, not endosomal trafficking.

Conclusions:

• HPV intracellular trafficking is a rapid process.
• The cell cycle state, particularly mitosis, significantly influences the timing of HPV nuclear entry and subsequent gene expression.
• Revises the understanding of HPV infectious entry kinetics.