A complex remodeling of cellular homeostasis distinguishes RSV/SARS-CoV-2 co-infected A549-hACE2 expressing cell lines
Authors:Claudia Vanetti1, Irma Saulle1,2, Valentina Artusa1,2, Claudia Moscheni1, Gioia Cappelletti1, Silvia Zecchini1, Sergio Strizzi1, Micaela Garziano1,2, Claudio Fenizia1,2, Antonella Tosoni1, Martina Broggiato1, Pasquale Ogno1, Manuela Nebuloni1, Mario Clerici2,3, Daria Trabattoni1, Fiona Limanaqi1 and Mara Biasin1
1 Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy. 2 Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. 3 Department of Biomedical and Clinical Sciences, Fondazione Don Carlo Gnocchi, IRCCS, Milan, Italy.
Keywords:
Respiratory Syncytial Virus (RSV), SARS-CoV-2, co-infection, cellular homeostasis, autophagy.
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Conflict of interest statement:
The authors declare that they have no competing interests.
Please cite this article as:
Claudia Vanetti, Irma Saulle, Valentina Artusa, Claudia Moscheni, Gioia Cappelletti, Silvia Zecchini, Sergio Strizzi, Micaela Garziano, Claudio Fenizia, Antonella Tosoni, Martina Broggiato, Pasquale Ogno, Manuela Nebuloni, Mario Clerici, Daria Trabattoni, Fiona Limanaqi, Mara Biasin (2024). A complex remodeling of cellular homeostasis distinguishes RSV/SARS-CoV-2 co-infected A549-hACE2 expressing cell lines. Microbial Cell 11: 353-367. doi: 10.15698/mic2024.10.838
© 2024 Vanetti et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Concurrent infections with two or more pathogens with analogous tropism, such as RSV and SARS-CoV-2, may antagonize or facilitate each other, modulating disease outcome. Clinically, discrepancies in the severity of symptoms have been reported in children with RSV/SARS-CoV-2 co-infection. Herein, we propose an in vitro co-infection model to assess how RSV/SARS-CoV-2 co- infection alters cellular homeostasis. To this end, A549-hACE2 expressing cells were either infected with RSV or SARS-CoV-2 alone or co-infected with both viruses. Viral replication was assessed at 72 hours post infection by droplet digital PCR, immunofluorescence, and transmission electron microscopy. Anti-viral/receptor/autophagy gene expression was evaluated by RT-qPCR and confirmed by secretome analyses and intracellular protein production. RSV/SARS- CoV-2 co-infection in A549-hACE2 cells was characterized by: 1) an increase in the replication rate of RSV compared to single infection; 2) an increase in one of the RSV host receptors, ICAM1; 3) an upregulation in the expression/secretion of pro-inflammatory genes; 4) a rise in the number and length of cellular conduits; and 5) augmented autophagosomes formation and/or alteration of the autophagy pathway. These findings suggest that RSV/SARS-CoV-2 co-infection model displays a unique and specific viral and molecular fingerprint and shed light on the viral dynamics during viral infection pathogenesis. This in vitro co-infection model may represent a potential attractive cost-effective approach to mimic both viral dynamics and host cellular responses, providing in future readily measurable targets predictive of co-infection progression.
doi: 10.15698/mic2024.10.838
Volume 11, pp. 353 to 367, published 08/10/2024.