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Volume 26
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10.3390/ijms262412174
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Review

Post-Translational Modifications in Respiratory Virus Infection: Recent Insights into the Development of In Vitro Models

by
Emna Ben Khlifa
1,
Alessia Campese
1,
Andrea Corsi
1,
Cristina Bombieri
1,
Maria Grazia Romanelli
1,
Maria Teresa Valenti
1,
Donato Zipeto
1,
Matteo Castelli
2,
Patricia Marie-Jeanne Lievens
1,† and
Alessandra Ruggiero
1,*,†
1
Department of Neurosciences, Biomedicine, and Movement Sciences, School of Medicine, University of Verona, Strada le Grazie 8, 37134 Verona, Italy
2
Laboratory of Microbiology and Virology, Vita-Salute San Raffaele University, 20132 Milan, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2025, 26(24), 12174; https://doi.org/10.3390/ijms262412174
Submission received: 6 November 2025 / Revised: 14 December 2025 / Accepted: 15 December 2025 / Published: 18 December 2025
(This article belongs to the Special Issue Viral Infections and Immune Responses)
Versions Notes

Abstract

Post-translational modifications (PTMs) are crucial chemical alterations occurring on proteins post-synthesis, impacting various cellular processes. During viral infections, PTMs are shown to play a multitude of roles in viral replication, host interaction, and immune evasion. Thus, these modifications can influence infectivity, with direct impact on the anti-viral host immune responses and potentially viral adaptation across species. This field is still scarcely explored, whilst understanding PTMs is not only important to advance the knowledge of virus pathology but also potentially to provide insights for vaccine development. In this review, we attempt to summarize the latest findings mainly published over the last 10 years, focusing on the roles of PTMs involved in virus infection and anti-viral immune responses, in the context of relevant human respiratory infections: influenza A virus (IAV), respiratory syncytial virus (RSV), and SARS-CoV-2. We decided to concentrate on these three viruses because they currently represent a global health problem due to recurrent outbreaks and pandemic potential. A deeper characterization of the PTMs may help in understanding virus–host interaction with possible implications on curative strategies. Further, we will report on cutting-edge technologies to study in vitro virus infection in different cellular-based systems. In particular, we describe and discuss the application of 2D and 3D lung organoid cell-culture systems as in vitro models to mimic respiratory environments and to study the PTMs in a controlled setting. Finally, we will discuss the importance of PTMs in the context of next-generation vaccine design, especially for their potential role to offer effective protection against respiratory viruses.
Keywords: post-translational modifications; emerging respiratory viruses; virus–host interaction; virus infection; organoids post-translational modifications; emerging respiratory viruses; virus–host interaction; virus infection; organoids

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MDPI and ACS Style

Ben Khlifa, E.; Campese, A.; Corsi, A.; Bombieri, C.; Romanelli, M.G.; Valenti, M.T.; Zipeto, D.; Castelli, M.; Lievens, P.M.-J.; Ruggiero, A. Post-Translational Modifications in Respiratory Virus Infection: Recent Insights into the Development of In Vitro Models. Int. J. Mol. Sci. 2025, 26, 12174. https://doi.org/10.3390/ijms262412174

AMA Style

Ben Khlifa E, Campese A, Corsi A, Bombieri C, Romanelli MG, Valenti MT, Zipeto D, Castelli M, Lievens PM-J, Ruggiero A. Post-Translational Modifications in Respiratory Virus Infection: Recent Insights into the Development of In Vitro Models. International Journal of Molecular Sciences. 2025; 26(24):12174. https://doi.org/10.3390/ijms262412174

Chicago/Turabian Style

Ben Khlifa, Emna, Alessia Campese, Andrea Corsi, Cristina Bombieri, Maria Grazia Romanelli, Maria Teresa Valenti, Donato Zipeto, Matteo Castelli, Patricia Marie-Jeanne Lievens, and Alessandra Ruggiero. 2025. "Post-Translational Modifications in Respiratory Virus Infection: Recent Insights into the Development of In Vitro Models" International Journal of Molecular Sciences 26, no. 24: 12174. https://doi.org/10.3390/ijms262412174

APA Style

Ben Khlifa, E., Campese, A., Corsi, A., Bombieri, C., Romanelli, M. G., Valenti, M. T., Zipeto, D., Castelli, M., Lievens, P. M.-J., & Ruggiero, A. (2025). Post-Translational Modifications in Respiratory Virus Infection: Recent Insights into the Development of In Vitro Models. International Journal of Molecular Sciences, 26(24), 12174. https://doi.org/10.3390/ijms262412174

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