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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Aging - 12(2020), 22 vom: 16. Nov., Seite 23017-23028

Sprache:

Englisch

Beteiligte Personen:

Han, Rui [VerfasserIn]
Hua, Chunting [VerfasserIn]
Sun, Siyuan [VerfasserIn]
Zhang, Boya [VerfasserIn]
Song, Yinjing [VerfasserIn]
van der Veen, Stijn [VerfasserIn]
Cheng, Hao [VerfasserIn]

Links:

Volltext

Themen:

Autophagy
Autophagy-Related Proteins
EC 2.7.1.1
EC 2.7.11.1
EC 2.7.11.24
Entry
Extracellular Signal-Regulated MAP Kinases
Human papillomavirus 11
Journal Article
Keratinocyte
MTOR protein, human
Proto-Oncogene Proteins c-akt
Pseudovirion
Research Support, Non-U.S. Gov't
TOR Serine-Threonine Kinases

Anmerkungen:

Date Completed 27.04.2021

Date Revised 04.12.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.18632/aging.104046

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM317652648