Proteomic landscape of SARS-CoV-2- and MERS-CoV-infected primary human renal epithelial cells.

Aneesha Kohli,Thomas Strecker,Sarah K Fehling,Helmut Geiger,Lucie Sauerhering,Patrick C Baer,Benjamin Koch,Stephan Becker,Kevin Klann,Christian Münch

doi:10.26508/lsa.202201371

Aneesha Kohli, Thomas Strecker + Show 8 more

Open Access

https://doi.org/10.26508/lsa.202201371

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Abstract

Acute kidney injury is associated with mortality in COVID-19 patients. However, host cell changes underlying infection of renal cells with SARS-CoV-2 remain unknown and prevent understanding of the molecular mechanisms that may contribute to renal pathology. Here, we carried out quantitative translatome and whole-cell proteomics analyses of primary renal proximal and distal tubular epithelial cells derived from human donors infected with SARS-CoV-2 or MERS-CoV to disseminate virus and cell type-specific changes over time. Our findings revealed shared pathways modified upon infection with both viruses, as well as SARS-CoV-2-specific host cell modulation driving key changes in innate immune activation and cellular protein quality control. Notably, MERS-CoV infection-induced specific changes in mitochondrial biology that were not observed in response to SARS-CoV-2 infection. Furthermore, we identified extensive modulation in pathways associated with kidney failure that changed in a virus- and cell type-specific manner. In summary, we provide an overview of the effects of SARS-CoV-2 or MERS-CoV infection on primary renal epithelial cells revealing key pathways that may be essential for viral replication.

Highlights

Since the dawn of the 21st century, the pathogenicity of coronaviruses has been affecting the world every few years through highly human-to-human transmissible viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) [1]
To demonstrate susceptibility of primary human renal proximal (PTC) and distal (DTC) tubular epithelial cells for SARS-CoV-2 or MERS-CoV infection, cells were grown in chamber slides and infected at an MOI of 0.01 to limit early onset of cytopathic effects and apoptosis [30]
Immunofluorescence staining confirmed the expression of the SARS-CoV-2 and MERS-CoV entry receptors angiotensin-converting enzyme 2 (ACE-2) and dipeptidyl-peptidase 4 (DPP4) [31], respectively, in PTC and DTC (Figs S1A–D and S2A–F)

Summary

Introduction

Since the dawn of the 21st century, the pathogenicity of coronaviruses has been affecting the world every few years through highly human-to-human transmissible viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) [1]. In 2019, the novel coronavirus SARS-CoV-2 emerged, resulting in the COVID-19 pandemic that continues to affect millions across the globe, with multiorgan failure being the most frequent cause of severe illness and death [2, 3]. Acute kidney injury (AKI) is reported in up to 78% of critically ill COVID-19 patients [5] and up to 90% in those who require mechanical ventilation [6]. AKI in SARS-CoV-2–infected patients is associated with increased morbidity and mortality, necessitating further research to understand the link between AKI and COVID-19 and the underlying mechanisms [5, 6, 7, 8]. Thought to be a primarily pulmonary disease, in the recent months, extrapulmonary tissues have been shown to be targeted by SARSCoV-2 during the systemic phase of COVID-19 [9]

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