Host factor PLAC8 is required for pancreas infection by SARS-CoV-2
Abstract Background Although COVID-19 initially caused great concern about respiratory symptoms, mounting evidence shows that also the pancreas is productively infected by SARS-CoV-2. However, the severity of pancreatic SARS-CoV-2 infection and its pathophysiology is still under debate. Here, we inv...
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| Format: | Article |
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Nature Portfolio
2025-02-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-00745-6 |
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| author | Lesly Ibargüen-González Sandra Heller Darío López-García Hanna Dietenberger Thomas FE Barth Patricia Gallego Israel Fernández-Cadenas Sayoa Alzate-Piñol Catalina Crespí Julieth A. Mena-Guerrero Eugenia Cisneros-Barroso Alejandro P. Ugalde Gabriel Bretones Charlotte Steenblock Alexander Kleger Marta L. DeDiego Carles Barceló |
| author_facet | Lesly Ibargüen-González Sandra Heller Darío López-García Hanna Dietenberger Thomas FE Barth Patricia Gallego Israel Fernández-Cadenas Sayoa Alzate-Piñol Catalina Crespí Julieth A. Mena-Guerrero Eugenia Cisneros-Barroso Alejandro P. Ugalde Gabriel Bretones Charlotte Steenblock Alexander Kleger Marta L. DeDiego Carles Barceló |
| author_sort | Lesly Ibargüen-González |
| collection | DOAJ |
| description | Abstract Background Although COVID-19 initially caused great concern about respiratory symptoms, mounting evidence shows that also the pancreas is productively infected by SARS-CoV-2. However, the severity of pancreatic SARS-CoV-2 infection and its pathophysiology is still under debate. Here, we investigate the consequences of SARS-CoV-2 pancreatic infection and the role of the host factor Placenta-associated protein (PLAC8). Methods We analyze plasma levels of pancreatic enzymes and inflammatory markers in a retrospective cohort study of 120 COVID-19 patients distributed in 3 severity-stratified groups. We study the expression of SARS-CoV-2 and PLAC8 in the pancreas of deceased COVID-19 patients as well as in non-infected donors. We perform pseudovirus infection experiments in PLAC8 knock-out PDAC and human beta cell-derived cell lines and validate results with SARS-CoV-2 virus. Results We find that analysis of circulating pancreatic enzymes aid the stratification of patients according to COVID-19 severity and predicts outcomes. Interestingly, we find an association between PLAC8 expression and SARS-CoV-2 infection in postmortem analysis of COVID-19 patients both in the pancreas and in other bonafide SARS-CoV-2 target tissues. Functional experiments demonstrate the requirement of PLAC8 in SARS-CoV-2 pancreatic productive infection by pseudovirus and full SARS-CoV-2 infectious virus inoculum from Wuhan-1 and BA.1 strains. Finally, we observe an overlap between PLAC8 and SARS-CoV-2 immunoreactivities in the pancreas of deceased patients. Conclusions Our data indicate the human pancreas as a SARS-CoV-2 target with plausible signs of injury and demonstrate that the host factor PLAC8 is required for SARS-CoV-2 pancreatic infection, thus defining new target opportunities for COVID-19-associated pancreatic pathogenesis. |
| format | Article |
| id | doaj-art-79686ef2949241d9b9b6c077d81ee12b |
| institution | Kabale University |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-79686ef2949241d9b9b6c077d81ee12b2025-02-09T12:52:07ZengNature PortfolioCommunications Medicine2730-664X2025-02-015111210.1038/s43856-025-00745-6Host factor PLAC8 is required for pancreas infection by SARS-CoV-2Lesly Ibargüen-González0Sandra Heller1Darío López-García2Hanna Dietenberger3Thomas FE Barth4Patricia Gallego5Israel Fernández-Cadenas6Sayoa Alzate-Piñol7Catalina Crespí8Julieth A. Mena-Guerrero9Eugenia Cisneros-Barroso10Alejandro P. Ugalde11Gabriel Bretones12Charlotte Steenblock13Alexander Kleger14Marta L. DeDiego15Carles Barceló16Translational Pancreatic Cancer Oncogenesis Group, Health Research Institute of the Balearic Islands (IdISBa), Hospital Universitari Son EspasesInstitute of Molecular Oncology and Stem Cell BiologyDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC)Department of Pathology, Ulm University HospitalDepartment of Pathology, Ulm University HospitalHospital Universitari Son EspasesStroke Pharmacogenomics and Genetics Group, Sant Pau Biomedical Research InstituteStroke Pharmacogenomics and Genetics Group, Sant Pau Biomedical Research InstituteHospital Universitari Son EspasesTranslational Pancreatic Cancer Oncogenesis Group, Health Research Institute of the Balearic Islands (IdISBa), Hospital Universitari Son EspasesHealth Research Institute of the Balearic Islands (IdISBa)Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología (IUOPA), Universidad de OviedoDepartamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología (IUOPA), Universidad de OviedoDepartment of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität DresdenInstitute of Molecular Oncology and Stem Cell BiologyDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC)Translational Pancreatic Cancer Oncogenesis Group, Health Research Institute of the Balearic Islands (IdISBa), Hospital Universitari Son EspasesAbstract Background Although COVID-19 initially caused great concern about respiratory symptoms, mounting evidence shows that also the pancreas is productively infected by SARS-CoV-2. However, the severity of pancreatic SARS-CoV-2 infection and its pathophysiology is still under debate. Here, we investigate the consequences of SARS-CoV-2 pancreatic infection and the role of the host factor Placenta-associated protein (PLAC8). Methods We analyze plasma levels of pancreatic enzymes and inflammatory markers in a retrospective cohort study of 120 COVID-19 patients distributed in 3 severity-stratified groups. We study the expression of SARS-CoV-2 and PLAC8 in the pancreas of deceased COVID-19 patients as well as in non-infected donors. We perform pseudovirus infection experiments in PLAC8 knock-out PDAC and human beta cell-derived cell lines and validate results with SARS-CoV-2 virus. Results We find that analysis of circulating pancreatic enzymes aid the stratification of patients according to COVID-19 severity and predicts outcomes. Interestingly, we find an association between PLAC8 expression and SARS-CoV-2 infection in postmortem analysis of COVID-19 patients both in the pancreas and in other bonafide SARS-CoV-2 target tissues. Functional experiments demonstrate the requirement of PLAC8 in SARS-CoV-2 pancreatic productive infection by pseudovirus and full SARS-CoV-2 infectious virus inoculum from Wuhan-1 and BA.1 strains. Finally, we observe an overlap between PLAC8 and SARS-CoV-2 immunoreactivities in the pancreas of deceased patients. Conclusions Our data indicate the human pancreas as a SARS-CoV-2 target with plausible signs of injury and demonstrate that the host factor PLAC8 is required for SARS-CoV-2 pancreatic infection, thus defining new target opportunities for COVID-19-associated pancreatic pathogenesis.https://doi.org/10.1038/s43856-025-00745-6 |
| spellingShingle | Lesly Ibargüen-González Sandra Heller Darío López-García Hanna Dietenberger Thomas FE Barth Patricia Gallego Israel Fernández-Cadenas Sayoa Alzate-Piñol Catalina Crespí Julieth A. Mena-Guerrero Eugenia Cisneros-Barroso Alejandro P. Ugalde Gabriel Bretones Charlotte Steenblock Alexander Kleger Marta L. DeDiego Carles Barceló Host factor PLAC8 is required for pancreas infection by SARS-CoV-2 Communications Medicine |
| title | Host factor PLAC8 is required for pancreas infection by SARS-CoV-2 |
| title_full | Host factor PLAC8 is required for pancreas infection by SARS-CoV-2 |
| title_fullStr | Host factor PLAC8 is required for pancreas infection by SARS-CoV-2 |
| title_full_unstemmed | Host factor PLAC8 is required for pancreas infection by SARS-CoV-2 |
| title_short | Host factor PLAC8 is required for pancreas infection by SARS-CoV-2 |
| title_sort | host factor plac8 is required for pancreas infection by sars cov 2 |
| url | https://doi.org/10.1038/s43856-025-00745-6 |
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