FABP5 Inhibitor Attenuates HPV11 Pseudovirion Infection by Reducing Lipid Droplet Formation

Area of Science:

• Virology
• Cell Biology
• Biochemistry

Background:

• Persistent low-risk human papillomavirus (HPV) infections cause skin and mucous membrane conditions like anogenital warts (AGW).
• Current understanding of HPV infection mechanisms is incomplete, hindering effective eradication and relapse prevention.
• HPV pseudovirions (PsV) are utilized to model the viral entry phase of infection.

Purpose of the Study:

• To investigate the role of Fatty Acid Binding Protein 5 (FABP5) in the early entry phase of low-risk HPV infection.
• To explore the association between HPV11 PsV infection and lipid metabolism in human keratinocytes.
• To evaluate the therapeutic potential of targeting FABP5 for HPV infection.

Main Methods:

• Utilized HPV11 pseudovirions (PsV) to model HPV entry in human keratinocytes.
• Assessed lipid droplet accumulation and FABP5 expression following PsV infection.
• Employed pharmacological inhibition of FABP5 in vitro.
• Investigated FABP5 levels and lipid droplet formation in a mouse vaginal model following PsV exposure.

Main Results:

• HPV11 PsV infection induced lipid droplet accumulation and FABP5 overexpression in human keratinocytes.
• Inhibition of FABP5 reduced lipid droplet accumulation and PsV readouts in vitro.
• In vivo, PsV exposure elevated FABP5 protein levels and lipid droplet formation in a mouse vaginal model.
• These findings highlight FABP5-mediated lipid metabolic alterations during early HPV11 entry.

Conclusions:

• Early HPV11 entry is associated with FABP5-mediated lipid metabolic alterations.
• FABP5 is a potential host factor for further investigation in HPV infection.
• Targeting FABP5 may offer a novel strategy for preventing and treating HPV infections.