Human Papillomavirus Minor Capsid Protein L2 Mediates Intracellular Trafficking into and Passage beyond the...

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• Human papillomaviruses (HPVs) are oncogenic viruses, with high-risk types like HPV16 linked to various cancers.
• The HPV minor capsid protein L2 is crucial for transporting viral DNA into the host cell nucleus.
• Understanding HPV intracellular trafficking is vital for developing new antiviral strategies.

Purpose of the Study:

• To investigate the function of specific amino acid residues (43-DQILQ-47) in the HPV16 L2 protein during intracellular trafficking.
• To determine the role of this sequence in viral DNA nuclear delivery.

Main Methods:

• Utilized pseudovirions with mutations in the HPV16 L2 43-DQILQ-47 sequence.
• Assessed viral binding, internalization, and infectivity in human keratinocytes.
• Tracked intracellular trafficking patterns and nuclear deposition of the viral pseudogenome.

Main Results:

• Mutations in the 43-DQILQ-47 sequence significantly reduced pseudovirion infectivity without affecting binding or internalization.
• Mutated pseudovirions showed altered trafficking, failing to reach the nucleus.
• These mutants did not interact with syntaxin 18, were retained in the endoplasmic reticulum (ER), and were routed to lysosomes.

Conclusions:

• The 43-DQILQ-47 sequence in HPV16 L2 is essential for efficient intracellular trafficking beyond the ER.
• This region plays a critical role in enabling the virus to bypass ER retention and reach the nucleus.
• Targeting this L2 sequence could offer a novel approach for antiviral therapies against HPV infections.