Inhibition by cellular vacuolar ATPase impairs human papillomavirus uncoating and infection

Area of Science:

• Cell Biology
• Virology
• Biochemistry

Background:

• Endosomal acidification is crucial for the infection cycle of several viruses, including human papillomaviruses (HPVs).
• The vacuolar ATPase (V-ATPase) enzyme complex is the primary driver of endosomal acidification within cells.
• V-ATPase represents a potential therapeutic target for developing novel antiviral agents against HPV infections.

Purpose of the Study:

• To investigate the role of V-ATPase in the lifecycle of human papillomaviruses.
• To evaluate the efficacy of V-ATPase inhibitors, including saliphenylhalamide and its derivatives, against different HPV types.
• To determine the specific stage of HPV infection affected by V-ATPase inhibition.

Main Methods:

• Utilized V-ATPase inhibitors, such as saliphenylhalamide and its derivatives, to treat relevant cell lines infected with various HPV types.
• Assessed the impact of V-ATPase inhibition on HPV endocytosis and uncoating processes.
• Quantified the infection inhibitory potencies and selectivity indices of different V-ATPase inhibitors across multiple HPV subtypes.

Main Results:

• Demonstrated that V-ATPase is a necessary component for successful HPV infection.
• Confirmed that V-ATPase inhibition specifically affects the uncoating/disassembly stage of the viral lifecycle, not endocytosis.
• Observed significant variations in selectivity indices among different V-ATPase inhibitors but low variation for a given inhibitor across HPV subtypes.

Conclusions:

• V-ATPase is a critical host factor required for human papillomavirus infection, specifically for viral uncoating.
• V-ATPase inhibitors exhibit broad-spectrum anti-HPV activity, suggesting their potential as a therapeutic strategy.
• Further research into V-ATPase inhibitors could lead to the development of effective treatments for a wide range of HPV infections.