Human Papillomavirus 16 Capsids Mediate Nuclear Entry during Infection

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Papillomaviruses (PVs), including oncogenic HPV16, are nonenveloped DNA viruses.
• Nuclear delivery of viral DNA is essential for PV infection establishment.
• Current understanding suggests PVs uncoat before nuclear entry.

Purpose of the Study:

• To investigate the integrity of HPV16 capsids during nuclear transport.
• To elucidate the mechanism of PV nuclear entry and disassembly.
• To challenge prevailing concepts of viral uncoating.

Main Methods:

• Electron microscopy to visualize viral capsids within vesicles and nuclei.
• Confocal analysis to determine factors influencing nuclear entry.
• In vivo studies using a murine cervicovaginal challenge model.

Main Results:

• HPV16 L1/L2 pseudovirions remain largely intact within vesicles during nuclear transport.
• Nuclear entry of L1 capsid protein depends on L2 but not on encapsidated DNA.
• Intact capsids associate with mitotic chromosomes and are found within interphase nuclei.
• In vivo studies confirm L1 nuclear localization and chromosome association.

Conclusions:

• A novel mechanism of viral nuclear entry involves largely intact capsids within transport vesicles.
• This challenges the traditional view of PV disassembly occurring before nuclear delivery.
• Findings provide new insights into viral strategies for accessing nuclear machinery and may inform antiviral development.