tetano
Editor, Senior Moderator
Front Cell Infect Microbiol
. 2024 Mar 25:14:1363407.
doi: 10.3389/fcimb.2024.1363407. eCollection 2024. 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
Benjamin Koch[SUP] 1 [/SUP], Mahmoud Shehata[SUP] 2 3 [/SUP], Christin Müller-Ruttloff[SUP] 3 4 [/SUP], Shady A Gouda[SUP] 5 [/SUP], Nils Wetzstein[SUP] 6 [/SUP], Sammy Patyna[SUP] 1 [/SUP], Anica Scholz[SUP] 7 [/SUP], Tobias Schmid[SUP] 7 [/SUP], Ursula Dietrich[SUP] 8 [/SUP], Christian Münch[SUP] 5 9 10 [/SUP], John Ziebuhr[SUP] 3 4 [/SUP], Helmut Geiger[SUP] 1 [/SUP], Luis Martinez-Sobrido[SUP] 11 [/SUP], Patrick C Baer[SUP] 1 [/SUP], Ahmed Mostafa[SUP] 2 11 [/SUP], Stephan Pleschka[SUP] 3 4 [/SUP]
Affiliations
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.
Keywords: acute kidney injury; distal tubular cells; influenza A virus; proteomics; regulated cell death; transcriptomics.
. 2024 Mar 25:14:1363407.
doi: 10.3389/fcimb.2024.1363407. eCollection 2024. 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
Benjamin Koch[SUP] 1 [/SUP], Mahmoud Shehata[SUP] 2 3 [/SUP], Christin Müller-Ruttloff[SUP] 3 4 [/SUP], Shady A Gouda[SUP] 5 [/SUP], Nils Wetzstein[SUP] 6 [/SUP], Sammy Patyna[SUP] 1 [/SUP], Anica Scholz[SUP] 7 [/SUP], Tobias Schmid[SUP] 7 [/SUP], Ursula Dietrich[SUP] 8 [/SUP], Christian Münch[SUP] 5 9 10 [/SUP], John Ziebuhr[SUP] 3 4 [/SUP], Helmut Geiger[SUP] 1 [/SUP], Luis Martinez-Sobrido[SUP] 11 [/SUP], Patrick C Baer[SUP] 1 [/SUP], Ahmed Mostafa[SUP] 2 11 [/SUP], Stephan Pleschka[SUP] 3 4 [/SUP]
Affiliations
- PMID: 38590437
- PMCID: PMC10999593
- DOI: 10.3389/fcimb.2024.1363407
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.
Keywords: acute kidney injury; distal tubular cells; influenza A virus; proteomics; regulated cell death; transcriptomics.