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Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells

ABSTRACT: Genetic differences are a primary reason for differences in the susceptibility and severity of COVID-19. As induced pluripotent stem (iPS) cells maintain the genetic information of the donor, they can be used to model individual differences in SARS-CoV-2 infection in vitro. We found that human iPS cells expressing the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) (ACE2-iPS cells) can be infected w SARS-CoV-2. In infected ACE2-iPS cells, the expression of SARS-CoV-2 nucleocapsid protein, budding of viral particles, and production of progeny virus, double membrane spherules, and double-membrane vesicles were confirmed. We performed SARS-CoV-2 infection experiments on ACE2-iPS/ embryonic stem (ES) cells from eight individuals. Male iPS/ES cells were more capable of producing the virus compared with female iPS/ES cells. These findings suggest that ACE2-iPS cells can not only reproduce individual differences in SARS-CoV-2 infection in vitro but also are a useful resource to clarify the causes of individual differences in COVID-19 due to genetic differences.

ORGANISM(S): Homo sapiens

PROVIDER: GSE166990 | GEO | 2021/04/18

REPOSITORIES: GEO

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Attenuation of SARS-CoV-2 Infection by Losartan in Human Kidney Organoids

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2022-01-23 | GSE149687 | GEO

Epithelial response to IFN-γ promotes SARS-CoV-2 infection

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2020-08-11 | GSE155241 | GEO

Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells

Project description:Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells

| PRJNA702533 | ENA

SARS-CoV-2 infects and replicates in photoreceptor and retinal ganglion cells of human retinal organoids

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Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection [RNA-seq]

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2020-10-05 | GSE154783 | GEO

Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection [ATAC-seq]

Project description:Identification of host genes essential for SARS-CoV-2 infection may reveal novel therapeutic targets and inform our understanding of COVID-19 pathogenesis. Here we performed a genome-wide CRISPR screen with SARS-CoV-2 in Vero-E6 cells, identifying known SARS-CoV-2 host factors including the receptor ACE2 and protease Cathepsin L. We additionally discovered novel pro-viral genes and pathways including the SWI/SNF chromatin remodeling complex, the alarmin HMGB1, and the transcription factors Smad3 and Smad4. Small molecule inhibitors of these pathways inhibited SARS-CoV-2-infection in both monkey and human cells, demonstrating the conserved role of these genetic hits across species. We also revealed that HMGB1 is a novel regulator of ACE2 expression and critical for SARS-CoV-2 replication. In contrast, loss of the histone H3.3 chaperone complex sensitized cells to virus-induced death. Together this study reveals potential therapeutic targets for SARS-CoV-2 and highlights host genes that may regulate COVID-19 pathogenesis.

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