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The Autophagy Cargo Receptor SQSTM1 Inhibits Infectious Bursal Disease Virus Infection through Selective Autophagic Degradation of Double-Stranded Viral RNA

Selective autophagy mediates the degradation of cytoplasmic cargos, such as damaged organelles, invading pathogens, and protein aggregates. However, whether it targets double-stranded RNA (dsRNA) of intracellular pathogens is still largely unknown. Here, we show that selective autophagy regulates th...

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Autores principales: Xu, Chenyang, Li, Tongtong, Lei, Jing, Zhang, Yina, Zhou, Jiyong, Hu, Boli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704251/
https://www.ncbi.nlm.nih.gov/pubmed/34960763
http://dx.doi.org/10.3390/v13122494
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author Xu, Chenyang
Li, Tongtong
Lei, Jing
Zhang, Yina
Zhou, Jiyong
Hu, Boli
author_facet Xu, Chenyang
Li, Tongtong
Lei, Jing
Zhang, Yina
Zhou, Jiyong
Hu, Boli
author_sort Xu, Chenyang
collection PubMed
description Selective autophagy mediates the degradation of cytoplasmic cargos, such as damaged organelles, invading pathogens, and protein aggregates. However, whether it targets double-stranded RNA (dsRNA) of intracellular pathogens is still largely unknown. Here, we show that selective autophagy regulates the degradation of the infectious bursal disease virus (IBDV) dsRNA genome. The amount of dsRNA decreased greatly in cells that overexpressed the autophagy-required protein VPS34 or autophagy cargo receptor SQSTM1, while it increased significantly in SQSTM1 or VPS34 knockout cells or by treating wild-type cells with the autophagy inhibitor chloroquine or wortmannin. Confocal microscopy and structured illumination microscopy showed SQSTM1 colocalized with dsRNA during IBDV infection. A pull-down assay further confirmed the direct binding of SQSTM1 to dsRNA through amino acid sites R139 and K141. Overexpression of SQSTM1 inhibited the replication of IBDV, while knockout of SQSTM1 promoted IBDV replication. Therefore, our findings reveal the role of SQSTM1 in clearing viral dsRNA through selective autophagy, highlighting the antiviral role of autophagy in the removal of the viral genome.
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spelling pubmed-87042512021-12-25 The Autophagy Cargo Receptor SQSTM1 Inhibits Infectious Bursal Disease Virus Infection through Selective Autophagic Degradation of Double-Stranded Viral RNA Xu, Chenyang Li, Tongtong Lei, Jing Zhang, Yina Zhou, Jiyong Hu, Boli Viruses Article Selective autophagy mediates the degradation of cytoplasmic cargos, such as damaged organelles, invading pathogens, and protein aggregates. However, whether it targets double-stranded RNA (dsRNA) of intracellular pathogens is still largely unknown. Here, we show that selective autophagy regulates the degradation of the infectious bursal disease virus (IBDV) dsRNA genome. The amount of dsRNA decreased greatly in cells that overexpressed the autophagy-required protein VPS34 or autophagy cargo receptor SQSTM1, while it increased significantly in SQSTM1 or VPS34 knockout cells or by treating wild-type cells with the autophagy inhibitor chloroquine or wortmannin. Confocal microscopy and structured illumination microscopy showed SQSTM1 colocalized with dsRNA during IBDV infection. A pull-down assay further confirmed the direct binding of SQSTM1 to dsRNA through amino acid sites R139 and K141. Overexpression of SQSTM1 inhibited the replication of IBDV, while knockout of SQSTM1 promoted IBDV replication. Therefore, our findings reveal the role of SQSTM1 in clearing viral dsRNA through selective autophagy, highlighting the antiviral role of autophagy in the removal of the viral genome. MDPI 2021-12-13 /pmc/articles/PMC8704251/ /pubmed/34960763 http://dx.doi.org/10.3390/v13122494 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xu, Chenyang
Li, Tongtong
Lei, Jing
Zhang, Yina
Zhou, Jiyong
Hu, Boli
The Autophagy Cargo Receptor SQSTM1 Inhibits Infectious Bursal Disease Virus Infection through Selective Autophagic Degradation of Double-Stranded Viral RNA
title The Autophagy Cargo Receptor SQSTM1 Inhibits Infectious Bursal Disease Virus Infection through Selective Autophagic Degradation of Double-Stranded Viral RNA
title_full The Autophagy Cargo Receptor SQSTM1 Inhibits Infectious Bursal Disease Virus Infection through Selective Autophagic Degradation of Double-Stranded Viral RNA
title_fullStr The Autophagy Cargo Receptor SQSTM1 Inhibits Infectious Bursal Disease Virus Infection through Selective Autophagic Degradation of Double-Stranded Viral RNA
title_full_unstemmed The Autophagy Cargo Receptor SQSTM1 Inhibits Infectious Bursal Disease Virus Infection through Selective Autophagic Degradation of Double-Stranded Viral RNA
title_short The Autophagy Cargo Receptor SQSTM1 Inhibits Infectious Bursal Disease Virus Infection through Selective Autophagic Degradation of Double-Stranded Viral RNA
title_sort autophagy cargo receptor sqstm1 inhibits infectious bursal disease virus infection through selective autophagic degradation of double-stranded viral rna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704251/
https://www.ncbi.nlm.nih.gov/pubmed/34960763
http://dx.doi.org/10.3390/v13122494
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