Research Paper Advance Articles

Autophagy is induced in human keratinocytes during human papillomavirus 11 pseudovirion entry

Rui Han1, *, , Chunting Hua1, *, , Siyuan Sun1, *, , Boya Zhang1, , Yinjing Song1, , Stijn van der Veen1,2, , Hao Cheng1, ,

  • 1 Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
  • 2 Department of Microbiology and Parasitology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou, China
* Equal contribution

Received: January 18, 2020       Accepted: June 25, 2020       Published: November 16, 2020      

https://doi.org/10.18632/aging.104046
How to Cite

Copyright: © 2020 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Human papillomavirus type 11 (HPV11) is one of the main causes of condyloma acuminatum, a widespread sexually transmitted disease. During infection of its primary target cell, keratinocytes, it is likely to encounter the autophagy pathway, which is an intracellular maintenance process that is also able to target invading pathogens. It is currently unknown whether HPV11 is targeted by autophagy or whether it is able to escape autophagy-mediated killing. Here, we investigated the autophagy response during HPV11 pseudovirion (PsV) entry in human keratinocytes. Transmission electron microscopy showed that intracellular PsVs were sequestered in lumen of double-membrane autophagosomes that subsequently appeared to fuse with lysosomes, while confocal microscopy showed induction LC3 puncta, the hallmark of induced autophagy activity. Furthermore, quantitative infection assays showed that high autophagy activity resulted in reduced HPV11 PsV infectivity. Therefore, the autophagy pathway seemed to actively target invading HPV11 PsVs for destruction in the autolysosome. Western analysis on the phosphorylation state of autophagy regulators and upstream pathways indicated that autophagy was activated through interplay between Erk and Akt signaling. In conclusion, autophagy functions as a cellular protection mechanism against intracellular HPV11 and therefore therapies that stimulate autophagy may prevent recurrent condyloma acuminatum by helping eliminate latent HPV11 infections.

Abbreviations

HPV: Human papillomavirus; PsV: Pseudovirion; NHEK: Normal human epidermal keratinocyte; TEM: Transmission electron microscope.