APA
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Ibargüen-González, L., Heller, S., López-García, D., Dietenberger, H., Barth, T., Gallego, P., … Barceló, C. (2025). Host factor PLAC8 is required for pancreas infection by SARS-CoV-2. Communications Medicine.
Chicago/Turabian
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Ibargüen-González, Lesly, S. Heller, Darío López-García, Hanna Dietenberger, T. Barth, Patricia Gallego, I. Férnandez-Cadenas, et al. “Host Factor PLAC8 Is Required for Pancreas Infection by SARS-CoV-2.” Communications Medicine (2025).
MLA
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Ibargüen-González, Lesly, et al. “Host Factor PLAC8 Is Required for Pancreas Infection by SARS-CoV-2.” Communications Medicine, 2025.
BibTeX Click to copy
@article{lesly2025a,
title = {Host factor PLAC8 is required for pancreas infection by SARS-CoV-2},
year = {2025},
journal = {Communications Medicine},
author = {Ibargüen-González, Lesly and Heller, S. and López-García, Darío and Dietenberger, Hanna and Barth, T. and Gallego, Patricia and Férnandez-Cadenas, I. and Alzate-Piñol, Sayoa and Crespi, C. and Mena-Guerrero, Julieth A and Cisneros-Barroso, Eugenia and Ugalde, Alejandro P and Bretones, G. and Steenblock, Charlotte and Kleger, A. and DeDiego, M. and Barceló, C.}
}
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). 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. 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. 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. SARS-CoV-2 virus can be found in the pancreas following infection. We investigated whether the pancreas is damaged by the infection and whether there are changes of the pancreatic enzymes that the pancreas produces and circulates around the rest of the body. A particular protein called the placenta-associated protein 8 (PLAC8) expression was found in people who died following SARS-CoV-2 infection. We show this protein is required for SARS-CoV-2 pancreatic infection and viral replication. PLAC8 could be further investigated as a target for drugs to treat COVID-19 that could reduce the impact on the pancreas. Ibargüen-González, Heller et al. analyze plasma levels of pancreatic enzymes and inflammatory markers in a retrospective cohort study of 120 COVID-19 patients. Host factor PLAC8 is found to be required for SARS-CoV-2 pancreatic infection.