Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study

Chu, Hin; Chan, Jasper Fuk‐Woo; Yuen, Terrence Tsz‐Tai; Shuai, Huiping; Yuan, Shuofeng; Wang, Yixin; Hu, Bingjie; Yip, Cyril Chik-Yan; Tsang, Jessica Oi-Ling; Huang, Xiner; Chai, Yue; Yang, Dong; Hou, Yuxin; Chik, Kenn Ka-Heng; Zhang, Xi; Fung, Agnes Yim-Fong; Tsoi, Hoi-Wah; Cai, Jian‐Piao; Chan, Wan-Mui; Ip, Jonathan Daniel; Chu, Allen Wing-Ho; Zhou, Jie; Lung, David Christopher; Kok, Kin‐Hang; To, Kelvin Kai‐Wang; Tsang, Owen Tak‐Yin; Chan, Kwok-Hung; Yuen, Kwok‐Yung

doi:10.1016/s2666-5247(20)30004-5

Cited by 739 publications

(850 citation statements)

References 33 publications

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“…To establish cell culture systems for studying SARS-CoV-2 replication and host cell responses, we examined the epithelial lung cancer cell lines, H1299 and Calu-3, as well as the epithelial colorectal adenocarcinoma cell line, Caco-2, which is frequently used as a coronavirus cell culture model [30][31][32]. Transfection of poly-I:C RNA, resulted in induction of IFIT1, IFIT2 and OAS2 (2'-5'-Oligoadenylate Synthetase 2) genes in Calu-3 and H1299 cells, indicating sensing of cytoplasmic foreign RNA is active in these cell types.…”

Section: Different Permissiveness Of Sars-cov-2 Infection In Cell Linesmentioning

confidence: 99%

Bulk and single-cell gene expression profiling of SARS-CoV-2 infected human cell lines identifies molecular targets for therapeutic intervention

Wyler

Mösbauer

Franke

et al. 2020

Preprint

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The coronavirus disease 2019 pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing global health threat with more than two million infected people since its emergence in late 2019. Detailed knowledge of the molecular biology of the infection is indispensable for understanding of the viral replication, host responses, and disease progression. We provide gene expression profiles of SARS-CoV and SARS-CoV-2 infections in three human cell lines (H1299, Caco-2 and Calu-3 cells), using bulk and single-cell transcriptomics. Small RNA profiling showed strong expression of the immunity and inflammation-associated microRNA miRNA-155 upon infection with both viruses. SARS-CoV-2 elicited approximately two-fold higher stimulation of the interferon response compared to SARS-CoV in the permissive human epithelial cell line Calu-3, and induction of cytokines such as CXCL10 or IL6. Single cell RNA sequencing data showed that canonical interferon stimulated genes such as IFIT2 or OAS2 were broadly induced, whereas interferon beta (IFNB1) and lambda (IFNL1-4) were expressed only in a subset of infected cells. In addition, temporal resolution of transcriptional responses suggested interferon regulatory factors (IRFs) activities precede that of nuclear factor-κB (NF-κB). Lastly, we identified heat shock protein 90 (HSP90) as a protein relevant for the infection. Inhibition of the HSP90 charperone activity by Tanespimycin/17-N-allylamino-17-demethoxygeldanamycin (17-AAG) resulted in a reduction of viral replication, and of TNF and IL1B mRNA levels. In summary, our study established in vitro cell culture models to study SARS-CoV-2 infection and identified HSP90 protein as potential drug target for therapeutic intervention of SARS-CoV-2 infection.

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Section: Different Permissiveness Of Sars-cov-2 Infection In Cell Linesmentioning

confidence: 99%

Bulk and single-cell gene expression profiling of SARS-CoV-2 infected human cell lines identifies molecular targets for therapeutic intervention

Wyler

Mösbauer

Franke

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Moreover, 78 percent of these SARS-CoV-2 exclusive PIPs were found produced by the enzymatic cleavage on the spike glycoproteins, the second most abundantly expressed transcript of the virus (Kim et al, 2020) . This finding suggests that high PIP concentrations might be released following SARS-CoV-2 huge replication rate from the outer and therefore accessible spike glycoproteins (Chu et al, 2020) . High production of these spike PIPs might be related to the excessive pulmonary inflammation observed in the patients .…”

Section: Main Textmentioning

confidence: 89%

Release of potential pro-inflammatory peptides from SARS-CoV-2 spike glycoproteins in neutrophil-extracellular traps

Blanco-Míguez

García

2020

Preprint

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COVID-2019 has progressed in around 10-15% of patients to an acute respiratory distress syndrome characterized by extensive pulmonary inflammation and elevated production of pro-inflammatory cytokines. Neutrophil activation seems to be crucial in the initiation and perpetuation of this exacerbated lung inflammation. However, the precise mechanisms by which this activation occurs remain yet elusive. To this end, this in silico study tried to identify potential proinflammatory inducing peptides (PIPs) produced by the action of the elastase released in neutrophil-extracellular traps over SARS-CoV-2 particles. We found nine potential PIPs exclusive from the SARS-CoV-2, showing homology against T cell recognition epitopes. Moreover, 78 percent of these exclusive PIPs were found produced by the enzymatic cleavage on the spike glycoproteins, suggesting that high PIP concentrations might be released following SARS-CoV-2 huge replication rate. Therefore, these PIPs might play a role in the exacerbated inflammatory response observed in some patients. Highlights• Nine potential PIPs were predicted exclusive from the SARS-CoV-2.• SARS-CoV-2 PIPs showed homology against T cell recognition epitopes. • Most of PIPs were produced by enzymatic cleavage of the spike glycoproteins. • The release of these PIPs might be related to the increased inflammatory response observed in the patients.

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“…We investigated the baseline expression levels of the SARS-CoV-2 host cell entry receptor ACE2 and the levels of seven types of leukocytes in 1,927 human lung tissue samples. Although SARS-CoV-2 cellular tropism is broad [16][17][18], we focused on lung tissue. In addition to epithelial cells elsewhere in the respiratory tract, alveolar epithelial cells are thought to be a primary SARS-CoV-2 entry point [16,28].…”

Section: Discussionmentioning

confidence: 99%

“…Epithelial cells of the respiratory tract, including the lung, are thought to be primary SARS-CoV-2 target cells [16][17][18]. These cells can sense viral infection via pattern recognition receptors (PRRs).…”

Section: Introductionmentioning

confidence: 99%

Low baseline pulmonary levels of cytotoxic lymphocytes as a predisposing risk factor for severe COVID-19

Duijf

2020

Preprint

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Coronavirus disease 19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and currently has detrimental human health, community and economic impacts around the world. In SARS-CoV-2-infected lung, induction of immune cell-recruiting cytokines is initially poor.When induction does occur, this may in fact exacerbate infection. These observations suggest that baseline levels of leukocytes, already residing in the lung prior to infection, may be important for orchestrating an effective early immune response. Hence, we performed "in silico flow cytometry" on 1,927 human lung tissues to deconvolute the levels of seven leukocyte types involved in triggering an acute anti-viral cellular immune response. Baseline levels of CD8+ T cells, resting natural killer (NK) cells and activated NK cells are significantly lower in lung tissues with high expression of the SARS-CoV-2 host cell entry receptor ACE2. We observe this in univariate analyses, in multivariate analyses that include sex, age, race, body mass index and smoking history, and in two independent datasets. Elevated ACE2 expression increases sensitivity to coronavirus infection. Thus, our results suggest that a subgroup of individuals may be exceedingly susceptible to COVID-19 due to concomitant high preexisting ACE2 expression and low baseline cytotoxic lymphocyte levels in the lung.

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Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study

Cited by 739 publications

References 33 publications

Bulk and single-cell gene expression profiling of SARS-CoV-2 infected human cell lines identifies molecular targets for therapeutic intervention

Bulk and single-cell gene expression profiling of SARS-CoV-2 infected human cell lines identifies molecular targets for therapeutic intervention

Release of potential pro-inflammatory peptides from SARS-CoV-2 spike glycoproteins in neutrophil-extracellular traps

Low baseline pulmonary levels of cytotoxic lymphocytes as a predisposing risk factor for severe COVID-19

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