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Porcine sapovirus-induced RIPK1-dependent necroptosis is proviral in LLC-PK cells
Sapoviruses belonging to the genus Sapovirus within the family Caliciviridae are commonly responsible for severe acute gastroenteritis in both humans and animals. Caliciviruses are known to induce intrinsic apoptosis in vitro and in vivo, however, calicivirus-induced necroptosis remains to be fully...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897573/ https://www.ncbi.nlm.nih.gov/pubmed/36735696 http://dx.doi.org/10.1371/journal.pone.0279843 |
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author | Sharif, Muhammad Baek, Yeong-Bin Nguyen, Thu Ha Soliman, Mahmoud Cho, Kyoung-Oh |
author_facet | Sharif, Muhammad Baek, Yeong-Bin Nguyen, Thu Ha Soliman, Mahmoud Cho, Kyoung-Oh |
author_sort | Sharif, Muhammad |
collection | PubMed |
description | Sapoviruses belonging to the genus Sapovirus within the family Caliciviridae are commonly responsible for severe acute gastroenteritis in both humans and animals. Caliciviruses are known to induce intrinsic apoptosis in vitro and in vivo, however, calicivirus-induced necroptosis remains to be fully elucidated. Here, we demonstrate that infection of porcine kidney LLC-PK cells with porcine sapovirus (PSaV) Cowden strain as a representative of caliciviruses induces receptor-interacting protein kinase 1 (RIPK1)-dependent necroptosis and acts as proviral compared to the antiviral function of PSaV-induced apoptosis. Infection of LLC-PK cells with PSaV Cowden strain showed that the interaction of phosphorylated RIPK1 (pRIPK1) with RIPK3 (pRIPK3), mixed lineage kinase domain-like protein (pMLKL) increased in a time-dependent manner, indicating induction of PSaV-induced RIPK1-dependent necroptosis. Interfering of PSaV-infected cells with each necroptotic molecule (RIPK1, RIPK3, or MLKL) by treatment with each specific chemical inhibitor or knockdown with each specific siRNA significantly reduced replication of PSaV but increased apoptosis and cell viability, implying proviral action of PSaV-induced necroptosis. In contrast, treatment of PSaV-infected cells with pan-caspase inhibitor Z-VAD-FMK increased PSaV replication and necroptosis, indicating an antiviral action of PSaV-induced apoptosis. These results suggest that PSaV-induced RIPK1-dependent necroptosis and apoptosis‒which have proviral and antiviral effects, respectively‒counterbalanced each other in virus-infected cells. Our study contributes to understanding the nature of PSaV-induced necroptosis and apoptosis and will aid in developing efficient and affordable therapies against PSaV and other calicivirus infections. |
format | Online Article Text |
id | pubmed-9897573 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-98975732023-02-04 Porcine sapovirus-induced RIPK1-dependent necroptosis is proviral in LLC-PK cells Sharif, Muhammad Baek, Yeong-Bin Nguyen, Thu Ha Soliman, Mahmoud Cho, Kyoung-Oh PLoS One Research Article Sapoviruses belonging to the genus Sapovirus within the family Caliciviridae are commonly responsible for severe acute gastroenteritis in both humans and animals. Caliciviruses are known to induce intrinsic apoptosis in vitro and in vivo, however, calicivirus-induced necroptosis remains to be fully elucidated. Here, we demonstrate that infection of porcine kidney LLC-PK cells with porcine sapovirus (PSaV) Cowden strain as a representative of caliciviruses induces receptor-interacting protein kinase 1 (RIPK1)-dependent necroptosis and acts as proviral compared to the antiviral function of PSaV-induced apoptosis. Infection of LLC-PK cells with PSaV Cowden strain showed that the interaction of phosphorylated RIPK1 (pRIPK1) with RIPK3 (pRIPK3), mixed lineage kinase domain-like protein (pMLKL) increased in a time-dependent manner, indicating induction of PSaV-induced RIPK1-dependent necroptosis. Interfering of PSaV-infected cells with each necroptotic molecule (RIPK1, RIPK3, or MLKL) by treatment with each specific chemical inhibitor or knockdown with each specific siRNA significantly reduced replication of PSaV but increased apoptosis and cell viability, implying proviral action of PSaV-induced necroptosis. In contrast, treatment of PSaV-infected cells with pan-caspase inhibitor Z-VAD-FMK increased PSaV replication and necroptosis, indicating an antiviral action of PSaV-induced apoptosis. These results suggest that PSaV-induced RIPK1-dependent necroptosis and apoptosis‒which have proviral and antiviral effects, respectively‒counterbalanced each other in virus-infected cells. Our study contributes to understanding the nature of PSaV-induced necroptosis and apoptosis and will aid in developing efficient and affordable therapies against PSaV and other calicivirus infections. Public Library of Science 2023-02-03 /pmc/articles/PMC9897573/ /pubmed/36735696 http://dx.doi.org/10.1371/journal.pone.0279843 Text en © 2023 Sharif et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Sharif, Muhammad Baek, Yeong-Bin Nguyen, Thu Ha Soliman, Mahmoud Cho, Kyoung-Oh Porcine sapovirus-induced RIPK1-dependent necroptosis is proviral in LLC-PK cells |
title | Porcine sapovirus-induced RIPK1-dependent necroptosis is proviral in LLC-PK cells |
title_full | Porcine sapovirus-induced RIPK1-dependent necroptosis is proviral in LLC-PK cells |
title_fullStr | Porcine sapovirus-induced RIPK1-dependent necroptosis is proviral in LLC-PK cells |
title_full_unstemmed | Porcine sapovirus-induced RIPK1-dependent necroptosis is proviral in LLC-PK cells |
title_short | Porcine sapovirus-induced RIPK1-dependent necroptosis is proviral in LLC-PK cells |
title_sort | porcine sapovirus-induced ripk1-dependent necroptosis is proviral in llc-pk cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897573/ https://www.ncbi.nlm.nih.gov/pubmed/36735696 http://dx.doi.org/10.1371/journal.pone.0279843 |
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