Nucleolin mediates SARS-CoV-2 replication and viral-induced apoptosis of host cells

Merino, Vanessa F.; Yu, Yanying; Ordoñez, Alvaro A.; Bullen, C. Korin; Lee, Albert; Saeki, Harumi; Ray, Krishanu; Huang, Tao; Jain, Sanjay; Pomper, Martin G.

doi:10.1016/j.antiviral.2023.105550

Cited by 12 publications

(8 citation statements)

References 77 publications

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“…The progression of nucleoli/nucleus size ratio was similar in Wuhan-infected and non-infected cells, as well as in syncytia triggered by Syncytin-1 (Figure 4A). In agreement with a recent report 39 , the nucleoli of Omicron-infected cells became larger, especially at a late time point of infection. This might reflect a recruitment of the nucleolar machinery to facilitate viral translation 40,41 .…”

Section: Resultssupporting

confidence: 93%

Dynamic label-free analysis of SARS-CoV-2 infection reveals virus-induced subcellular remodeling

Saunders,

Monel,

Cayet

et al. 2023

Preprint

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SummaryAssessing the impact of SARS-CoV-2 on organelle dynamics allows a better understanding of the mechanisms of viral replication. We combine label-free holo-tomographic microscopy (HTM) with Artificial Intelligence (AI) to visualize and quantify the subcellular changes triggered by SARS-CoV-2 infection. We study the dynamics of shape, position and dry mass of nucleoli, nuclei, lipid droplets (LD) and mitochondria within hundreds of single cells from early infection to syncytia formation and death. SARS-CoV-2 infection enlarges nucleoli, perturbs LD, changes mitochondrial shape and dry mass, and separates LD from mitochondria. We then used Bayesian statistics on organelle dry mass states to define organelle cross-regulation (OCR) networks and report modifications of OCR that are triggered by infection and syncytia formation. Our work highlights the subcellular remodeling induced by SARS-CoV-2 infection and provides a new AI-enhanced, label-free methodology to study in real-time the dynamics of cell populations and their content.

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Section: Resultssupporting

confidence: 93%

Dynamic label-free analysis of SARS-CoV-2 infection reveals virus-induced subcellular remodeling

Saunders,

Monel,

Cayet

et al. 2023

Preprint

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“…Furthermore, it interacts with SARS-CoV-2 proteins, such as N and S genes and Nsp1 and Nsp12 proteins. This interaction was suggested to mediate SARS-CoV-2 induction of p53-dependent apoptosis ( Merino et al, 2023 ). We observed that NCL expression was significantly decreased in all datasets from patients with severe COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of RNA-seq datasets reveals novel targets and regulators of COVID-19 severity

Oliveira,

Freitas,

de Medeiros

et al. 2024

Life Sci. Alliance

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During the COVID-19 pandemic, RNA-seq datasets were produced to investigate the virus–host relationship. However, much of these data remains underexplored. To improve the search for molecular targets and biomarkers, we performed an integrated analysis of multiple RNA-seq datasets, expanding the cohort and including patients from different countries, encompassing severe and mild COVID-19 patients. Our analysis revealed that severe COVID-19 patients exhibit overexpression of genes coding for proteins of extracellular exosomes, endomembrane system, and neutrophil granules (e.g.,S100A9,LY96, andRAB1B), which may play an essential role in the cellular response to infection. Concurrently, these patients exhibit down-regulation of genes encoding components of the T cell receptor complex and nucleolus, includingTP53,IL2RB, andNCL. Finally, SPI1 may emerge as a central transcriptional factor associated with the up-regulated genes, whereas TP53, MYC, and MAX were associated with the down-regulated genes during COVID-19. This study identified targets and transcriptional factors, lighting on the molecular pathophysiology of syndrome coronavirus 2 infection.

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“…It is likely that other oxygen sensitive pathways, such as chromatin conformation and DNA methylation may further modulate NCL expression in hypoxic conditions. NCL was reported to interact with Influenza virus non-structural protein 1 and to regulate late viral gene expression 69,70 , and to also mediate SARS-CoV-2 replication 71 , suggesting a wide-ranging impact for the hypoxic regulation of NCL in respiratory infections.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia inducible factors inhibit respiratory syncytial virus infection by modulation of nucleolin expression

Zhuang,

Gallo,

Sharma

et al. 2023

Preprint

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Respiratory syncytial virus (RSV) is a global healthcare problem, causing respiratory illness in young children and elderly individuals. However, our knowledge of the host pathways that define susceptibility to RSV infection and disease severity is limited. Hypoxia inducible factors (HIFs) define cellular metabolic processes in response to low oxygen and are recognised to play a key role in regulating inflammatory responses in the lower respiratory tract. We demonstrate a role for hypoxia inducible factors (HIFs) to suppress RSV entry and RNA replication. We show that hypoxia and HIF prolyl-hydroxylase inhibitors significantly reduce expression of the RSV entry receptor nucleolin and inhibit viral driven cell-cell fusion. We identify a HIF regulated microRNA, miR-494, that regulates nucleolin expression. In RSV-infected mice, treatment with the clinically approved HIF prolyl-hydroxylase inhibitor, Daprodustat, reduced the level of infectious virus and infiltrating monocytes and neutrophils in the lung. This study highlights a role for HIF-signalling to limit multiple aspects of RSV infection and associated inflammation and informs future therapeutic approaches for treating this respiratory pathogen.

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Nucleolin mediates SARS-CoV-2 replication and viral-induced apoptosis of host cells

Cited by 12 publications

References 77 publications

Dynamic label-free analysis of SARS-CoV-2 infection reveals virus-induced subcellular remodeling

Dynamic label-free analysis of SARS-CoV-2 infection reveals virus-induced subcellular remodeling

Integrated analysis of RNA-seq datasets reveals novel targets and regulators of COVID-19 severity

Hypoxia inducible factors inhibit respiratory syncytial virus infection by modulation of nucleolin expression

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