Effect of Short Time of SARS-CoV-2 Infection in Caco-2 Cells

Zupin, Luisa; Fontana, Francesco; Clemente, Libera; Ruscio, Maurizio; Ricci, Giuseppe; Crovella, Sérgio

doi:10.3390/v14040704

Cited by 10 publications

(8 citation statements)

References 18 publications

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“…2E” in Shuai et al (2020) , respectively. The absence of cytopathic effect during SARS-CoV-2 infection in Caco-2 cells was also reported in multiple studies by other research groups ( Wurtz et al, 2021 ; Zupin et al, 2022 ; Alexander et al, 2020 ; Bartolomeo et al, 2022 ; Saccon et al, 2021 ), including results for the Delta ( Mautner et al, 2022 ) and the Omicron ( Dighe et al, 2022 ) variants.…”

Section: Methodssupporting

confidence: 69%

Development of a novel mathematical model that explains SARS-CoV-2 infection dynamics in Caco-2 cells

Staroverov

Nersisyan

Galatenko

et al. 2023

PeerJ

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Mathematical modeling is widely used to study within-host viral dynamics. However, to the best of our knowledge, for the case of SARS-CoV-2 such analyses were mainly conducted with the use of viral load data and for the wild type (WT) variant of the virus. In addition, only few studies analyzed models for in vitro data, which are less noisy and more reproducible. In this work we collected multiple data types for SARS-CoV-2-infected Caco-2 cell lines, including infectious virus titers, measurements of intracellular viral RNA, cell viability data and percentage of infected cells for the WT and Delta variants. We showed that standard models cannot explain some key observations given the absence of cytopathic effect in human cell lines. We propose a novel mathematical model for in vitro SARS-CoV-2 dynamics, which included explicit modeling of intracellular events such as exhaustion of cellular resources required for virus production. The model also explicitly considers innate immune response. The proposed model accurately explained experimental data. Attenuated replication of the Delta variant in Caco-2 cells could be explained by our model on the basis of just two parameters: decreased cell entry rate and increased cytokine production rate.

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Section: Methodssupporting

confidence: 69%

Development of a novel mathematical model that explains SARS-CoV-2 infection dynamics in Caco-2 cells

Staroverov

Nersisyan

Galatenko

et al. 2023

PeerJ

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“…No relative increase in these cytokines/chemokines was observed in Calu-3 cells infected with SARS-CoV-2 (Shuai et al, 2020). Other authors suggest that the absence of CPE in Caco-2 could be due to the weak proinflammatory response triggered by SARS-CoV-2 (Zupin et al, 2022).…”

Section: Cancer Coli 2 Cells (Caco-2)mentioning

confidence: 94%

“…The absence of CPE in Caco-2 cells is suggested at least for low multiplicity of infections (MOIs) (Chu et al, 2020;Saccon et al, 2021;Wurtz et al, 2021;Mautner et al, 2022;Zupin et al, 2022) and this is its main disadvantage compared to Vero E6 cells. Furthermore, unlike Calu-3 cells, SARS-CoV-2 viral production by Caco-2 cells typically reaches levels similar to or higher than those seen in Vero E6 cells (Figure 2) (Chu et al, 2020;Koch et al, 2021;Saccon et al, 2021;de Souza et al, 2022).…”

Section: Cancer Coli 2 Cells (Caco-2)mentioning

confidence: 99%

Choosing a cellular model to study SARS-CoV-2

Souza

Bideau

Boschi

et al. 2022

Front. Cell. Infect. Microbiol.

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As new pathogens emerge, new challenges must be faced. This is no different in infectious disease research, where identifying the best tools available in laboratories to conduct an investigation can, at least initially, be particularly complicated. However, in the context of an emerging virus, such as SARS-CoV-2, which was recently detected in China and has become a global threat to healthcare systems, developing models of infection and pathogenesis is urgently required. Cell-based approaches are crucial to understanding coronavirus infection biology, growth kinetics, and tropism. Usually, laboratory cell lines are the first line in experimental models to study viral pathogenicity and perform assays aimed at screening antiviral compounds which are efficient at blocking the replication of emerging viruses, saving time and resources, reducing the use of experimental animals. However, determining the ideal cell type can be challenging, especially when several researchers have to adapt their studies to specific requirements. This review strives to guide scientists who are venturing into studying SARS-CoV-2 and help them choose the right cellular models. It revisits basic concepts of virology and presents the currently available in vitro models, their advantages and disadvantages, and the known consequences of each choice.

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“…Considering all previous studies on different viruses and the current data on SARS-CoV-2, we aimed at dissecting the role of EGFR–RAS–MAPK axis in viral infection. First, we monitored MAPK activation in response to a treatment with His-tagged recombinant spike receptor binding domain (Spike-RBD) in Caco-2 cells, which have high level of ACE2 ( Fig S1A ), express ADAM17 , TMPRSS2 and FURIN ( Fig S1B ) that were previously described as key players in viral infection, and are highly permissive for SARS-CoV-2 ( Zupin et al, 2022 ) ( Fig S1C ). Spike-RBD treatment led to an increased activation of the key mediators of MAPK signaling, such as ERK1/2 and CRAF, after 10 min of incubation, whereas at later time points, activation returned to a basal level ( Fig 1A and B ).…”

Section: Resultsmentioning

confidence: 99%

ACE2-EGFR-MAPK signaling contributes to SARS-CoV-2 infection

Engler

Albers²,

Maltitz³

et al. 2023

Life Sci. Alliance

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SARS-CoV-2 triggered the most severe pandemic of recent times. To enter into a host cell, SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2). However, subsequent studies indicated that other cell membrane receptors may act as virus-binding partners. Among these receptors, the epidermal growth factor receptor (EGFR) was hypothesized not only as a spike protein binder, but also to be activated in response to SARS-CoV-2. In our study, we aim at dissecting EGFR activation and its major downstream signaling pathway, the mitogen-activated signaling pathway (MAPK), in SARS-CoV-2 infection. Here, we demonstrate the activation of EGFR–MAPK signaling axis by the SARS-CoV-2 spike protein and we identify a yet unknown cross talk between ACE2 and EGFR that regulated ACE2 abundance and EGFR activation and subcellular localization, respectively. By inhibiting the EGFR-MAPK activation, we observe a reduced infection with either spike-pseudotyped particles or authentic SARS-CoV-2, thus indicating that EGFR serves as a cofactor and the activation of EGFR-MAPK contributes to SARS-CoV-2 infection.

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Effect of Short Time of SARS-CoV-2 Infection in Caco-2 Cells

Cited by 10 publications

References 18 publications

Development of a novel mathematical model that explains SARS-CoV-2 infection dynamics in Caco-2 cells

Development of a novel mathematical model that explains SARS-CoV-2 infection dynamics in Caco-2 cells

Choosing a cellular model to study SARS-CoV-2

ACE2-EGFR-MAPK signaling contributes to SARS-CoV-2 infection

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