Work

Pathogenesis of Human Papillomaviruses Requires the ATR/p62 Autophagy-Related Pathway

Year: 2020

Type: article

Abstract: High-risk human papillomaviruses (HPVs) infect epithelial cells and induce viral genome amplification upon differentiation. HPV proteins activate the ATR DNA damage repair pathway, and this is required for HPV genome amplification. In the present study, we show that HPV-induced ATR activation also leads to suppression of expression of inflammatory response genes. This suppression results from HPV-induced phosphorylation of the autophagosome cargo protein p62 which regulates the levels of the transcription factor GATA4. Activation of p62 in normal fibroblasts results in senescence, but this is not seen in HPV-positive keratinocytes. Importantly, knockdown of p62 or overexpression of GATA4 in HPV-positive cells abrogates viral replication. This study demonstrates that activation of ATR in HPV-positive cells triggers a p62-directed pathway inducing suppression of inflammatory gene expression independent of DNA repair and facilitating HPV replication.

Source: mBio

DOI: 10.1128/mbio.01628-20

Authors: Shiyuan Hong, Yan Li, Paul J. Kaminski, Jorge Andrade, Laimonis A. Laimins

Institutions: Northwestern University, University of Chicago

Language: English

Topic: Cervical Cancer and HPV Research

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,900