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

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.

SARS-CoV-2 Variants Show Different Host Cell Proteome Profiles With Delayed Immune Response Activation in Omicron-Infected Cells

“…Therefore, we cannot expand our findings to the currently dominating variants BA.4 and BA.5 without future analyses. Additional studies will be required to transfer our findings to different primary cells and tissues, which have been shown to show differences in host cell responses ( 51 ).…”

Choosing a cellular model to study SARS-CoV-2

“…Although primary HAE cells have gained prominence in studies of SARS-CoV-2, which is a respiratory virus, other primary cultures, such as primary human renal epithelial cells (Kohli et al, 2022), primary ocular cells (Eriksen et al, 2021preprint;Eriksen et al, 2022), human peripheral blood mononuclear cells (PBMCs) (Pontelli et al, 2022) and human pancreatic progenitors (Szlachcic et al, 2022) are permissive to SARS-CoV-2. The range of primary cells permissive to SARS-CoV-2 opens the way for in vitro studies of more complex cellular organisations, such as organoids.…”

Discovery of Initial SARS-CoV-2 as DNA Viruses and Reliable Interactive COVID-19 DNA Methylation Markers and Druggable Targets and Potential Malignant Diseases with Long Incubation Period

“…A comparison study of the viral phylogenetic trees of known pandemic coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2), as well as pandemic influenza A strains (H1N1, H3N2 and H5N10) revealed that SARS-CoV-2 is most closely related to SARS-CoV and MERS-CoV [17]. We found that DNA methylations' marker genes MX1 and PARP9 identified for SARS-CoV-2 have been rooted in SARS-CoV and MERS-CoV [18][19][20], which indicates that the initial SARS-CoV-2 may be better treated as transcribed viral DNA into RNA virus due to the long incubation feature of MX1 associated diseases, i.e., not as a positive-strand RNA virus that has been concerned by scientists. Such a discovery will significantly change the scientific thinking and knowledge of viruses.…”

“…Solving S4 classifiers (4), we get Table 8 as follows. We note that PARP9 was linked to SARS-CoV-1 and MERS-CoV in the literature [18][19][20]35,36]. It has also been extensively studied its connection to SARS-CoV-2 [37][38][39][40].…”

“…It was found that the ADP-ribose-10-monophosphatase domains of SARS-CoV and human coronavirus 229E (HCoV-229E) mediate resistance to antiviral interferon responses [35]. It was found that proteins PARP9 and MX1 to be shared across SARS-CoV-2-infected PTC and DTC as well as MERS-CoV-infected PTC [20]. Expressions of MX1 appeared in targets of IFNg pathway in response to viral infection SARS-CoV-1 and SARS-CoV-2.…”