FABP5 Inhibitor Attenuates HPV11 Pseudovirion Infection by Reducing Lipid Droplet Formation

Persistent infection with low-risk human papillomavirus (HPV) can result in conditions such as verrucous hyperplasia of the skin and mucous membranes. Among these, anogenital warts (AGW), primarily caused by HPV types 6 and 11, are common sexually transmitted infections with a high recurrence rate. Because early infection with HPV often lacks obvious symptoms and the PsV model primarily reflects the entry phase, timely diagnosis and treatment of full HPV infection are difficult. The incomplete understanding of HPV infection mechanisms highlights the need for further investigation to address challenges in eradicating infection and preventing relapse. HPV pseudovirions (PsV) are commonly used to model viral entry. In our study, HPV11 PsV infection was found to induce lipid droplet accumulation in human keratinocytes, accompanied by overexpression of FABP5, a protein involved in fatty acid uptake, transport, and metabolism. To date, the role of FABP5 in low-risk HPV infection has not been reported. To avoid overstatement and to reflect the PsV model system, we focused on the entry phase of infection. Pharmacological inhibition of FABP5 reduced lipid droplet accumulation and PsV readouts in vitro, while in vivo, PsV exposure in a mouse vaginal model led to elevated FABP5 protein levels and lipid droplet formation. These findings suggest that early HPV11 entry is associated with FABP5-mediated lipid metabolic alterations and that FABP5 represents a promising host factor for further validation. Our study demonstrates that inhibition of FABP5 reduces HPV11 PsV infection readouts, indicating that targeting FABP5 may provide a novel strategy for the prevention and treatment of HPV infection.