Influenza A virus replicates productively in primary human kidney cells and induces factors and mechanisms related to regulated cell death and renal pathology observed in virus-infected patients.

Autor:	Koch B; Department of Internal Medicine 4, Nephrology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany., Shehata M; Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Cairo, Egypt.; Institute of Medical Virology, Justus Liebig University Giessen, Giessen, Germany., Müller-Ruttloff C; Institute of Medical Virology, Justus Liebig University Giessen, Giessen, Germany.; German Center for Infection Research (DZIF), Partner Site Giessen, Giessen, Germany., Gouda SA; Institute for Biochemistry II, Goethe University Frankfurt, Frankfurt am Main, Germany., Wetzstein N; Department of Internal Medicine 2, Infectious Diseases, Goethe University Frankfurt, Frankfurt am Main, Germany., Patyna S; Department of Internal Medicine 4, Nephrology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany., Scholz A; Institute of Biochemistry I, Goethe University Frankfurt, Frankfurt am Main, Germany., Schmid T; Institute of Biochemistry I, Goethe University Frankfurt, Frankfurt am Main, Germany., Dietrich U; Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, Frankfurt am Main, Germany., Münch C; Institute for Biochemistry II, Goethe University Frankfurt, Frankfurt am Main, Germany.; Frankfurt Cancer Institute (FCI), Frankfurt am Main, Germany.; Cardio-Pulmonary Institute, Frankfurt am Main, Germany., Ziebuhr J; Institute of Medical Virology, Justus Liebig University Giessen, Giessen, Germany.; German Center for Infection Research (DZIF), Partner Site Giessen, Giessen, Germany., Geiger H; Department of Internal Medicine 4, Nephrology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany., Martinez-Sobrido L; Texas Biomedical Research Institute, Disease Intervention & Prevention (DIP) and Host Pathogen Interactions (HPI) Programs, San Antonio, TX, United States., Baer PC; Department of Internal Medicine 4, Nephrology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany., Mostafa A; Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Cairo, Egypt.; Texas Biomedical Research Institute, Disease Intervention & Prevention (DIP) and Host Pathogen Interactions (HPI) Programs, San Antonio, TX, United States., Pleschka S; Institute of Medical Virology, Justus Liebig University Giessen, Giessen, Germany.; German Center for Infection Research (DZIF), Partner Site Giessen, Giessen, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2024 Mar 25; Vol. 14, pp. 1363407. Date of Electronic Publication: 2024 Mar 25 (Print Publication: 2024).
DOI:	10.3389/fcimb.2024.1363407
Abstrakt:	Introduction: Influenza A virus (IAV) infection can cause the often-lethal acute respiratory distress syndrome (ARDS) of the lung. Concomitantly, acute kidney injury (AKI) is frequently noticed during IAV infection, correlating with an increased mortality. The aim of this study was to elucidate the interaction of IAV with human kidney cells and, thereby, to assess the mechanisms underlying IAV-mediated AKI. Methods: To investigate IAV effects on nephron cells we performed infectivity assays with human IAV, as well as with human isolates of either low or highly pathogenic avian IAV. Also, transcriptome and proteome analysis of IAV-infected primary human distal tubular kidney cells (DTC) was performed. Furthermore, the DTC transcriptome was compared to existing transcriptomic data from IAV-infected lung and trachea cells. Results: We demonstrate productive replication of all tested IAV strains on primary and immortalized nephron cells. Comparison of our transcriptome and proteome analysis of H1N1-type IAV-infected human primary distal tubular cells (DTC) with existing data from H1N1-type IAV-infected lung and primary trachea cells revealed enrichment of specific factors responsible for regulated cell death in primary DTC, which could be targeted by specific inhibitors. Discussion: IAV not only infects, but also productively replicates on different human nephron cells. Importantly, multi-omics analysis revealed regulated cell death as potential contributing factor for the clinically observed kidney pathology in influenza. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Koch, Shehata, Müller-Ruttloff, Gouda, Wetzstein, Patyna, Scholz, Schmid, Dietrich, Münch, Ziebuhr, Geiger, Martinez-Sobrido, Baer, Mostafa and Pleschka.)
Databáze:	MEDLINE
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