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1.
Life Sci Alliance ; 5(5)2022 05.
Article in English | MEDLINE | ID: covidwho-1675573

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.


Subject(s)
Epithelial Cells/metabolism , Epithelial Cells/virology , Kidney , Middle East Respiratory Syndrome Coronavirus/physiology , Proteome , Proteomics , SARS-CoV-2/physiology , Biomarkers , COVID-19/metabolism , COVID-19/virology , Cell Nucleus/genetics , Cell Nucleus/metabolism , Cells, Cultured , Computational Biology/methods , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Gene Expression Regulation , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Kidney Tubules, Distal , Kidney Tubules, Proximal , Mitochondria/genetics , Mitochondria/metabolism , Primary Cell Culture , Proteomics/methods , Virus Replication
2.
Biointerphases ; 15(6): 061005, 2020 11 17.
Article in English | MEDLINE | ID: covidwho-934052

ABSTRACT

The emergence of SARS-CoV-2 highlights the global need for platform technologies to enable the rapid development of diagnostics, vaccines, treatments, and personal protective equipment (PPE). However, many current technologies require the detailed mechanistic knowledge of specific material-virion interactions before they can be employed, for example, to aid in the purification of vaccine components or in the design of a more effective PPE. Here, we show that an adaption of a polymer microarray method for screening bacterial-surface interactions allows for the screening of polymers for desirable material-virion interactions. Nonpathogenic virus-like particles including fluorophores are exposed to the arrays in an aqueous buffer as a simple model of virions carried to the surface in saliva/sputum. Competitive binding of Lassa and Rubella virus-like particles is measured to probe the relative binding properties of a selection of copolymers. This provides the first step in the development of a method for the discovery of novel materials with promise for viral binding, with the next being development of this method to assess absolute viral adsorption and assessment of the attenuation of the activity of live virus, which we propose would be part of a material scale up step carried out in high containment facilities, alongside the use of more complex media to represent biological fluids.


Subject(s)
Microarray Analysis , Polymers/chemistry , Virion/isolation & purification , Adsorption , COVID-19 , Coronavirus Infections/diagnosis , Pandemics , Pneumonia, Viral/diagnosis , Ultraviolet Rays
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