Overexpression of the nucleocapsid protein of Middle East respiratory syndrome coronavirus up-regulates CXCL10

Aboagye, James; Yew, Chow Wenn; Ng, Oi-Wing; Monteil, Vanessa; Mirazimi, Alì; Tan, Yee‐Joo

doi:10.1042/bsr20181059

Cited by 16 publications

(12 citation statements)

References 23 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its function involves entering the host cells, binding to the viral RNA genome and forms the ribonucleoprotein core to facilitate its replication and process the virus particle assembly and release 27 . Previous reports showed that the N protein from SARS-CoV and MERS-CoV were highly inflammatory nature to promote the expression of inflammatory cytokines, chemokines, prothrombinase and were able to induce acute lung inflammation in mouse model [28][29][30] . The N protein from hantavirus Andes virus increased basal endothelial cell permeability by activating RhoA signaling 31 .…”

Section: Discussionmentioning

confidence: 99%

Direct activation of endothelial cells by SARS-CoV-2 nucleocapsid protein is blocked by Simvastatin

Qian

Lei

Patel

et al. 2021

Preprint

View full text Add to dashboard Cite

Emerging evidence suggests that endothelial activation plays a central role in the pathogenesis of acute respiratory distress syndrome (ARDS) and multi-organ failure in patients with COVID-19. However, the molecular mechanisms underlying endothelial activation in COVID-19 patients remain unclear. In this study, the SARS-CoV-2 viral proteins that potently activate human endothelial cells were screened to elucidate the molecular mechanisms involved with endothelial activation. It was found that nucleocapsid protein (NP) of SARS-CoV-2 significantly activated human endothelial cells through TLR2/NF-κB and MAPK signaling pathways. Moreover, by screening a natural microbial compound library containing 154 natural compounds, simvastatin was identified as a potent inhibitor of NP-induced endothelial activation. Remarkablely, though the protein sequences of N proteins from coronaviruses are highly conserved, only NP from SARS-CoV-2 induced endothelial activation. The NPs from other coronaviruses such as SARS-CoV, MERS-CoV, HUB1-CoV and influenza virus H1N1 did not affect endothelial activation. These findings are well consistent with the results from clinical investigations showing broad endotheliitis and organ injury in severe COVID-19 patients. In conclusion, the study provides insights on SARS-CoV-2-induced vasculopathy and coagulopathy, and suggests that simvastatin, an FDA-approved lipid-lowering drug, may benefit to prevent the pathogenesis and improve the outcome of COVID-19 patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Direct activation of endothelial cells by SARS-CoV-2 nucleocapsid protein is blocked by Simvastatin

Qian

Lei

Patel

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…In another in vitro study [ 157 ], it was seen that SARS-CoV infection could activate the chemokines of lung traffic, IL8 and IL17, through TLR9, which would cause symptoms and also monocyte-macrophage activation and coagulation upregulation. In a study on MERS-CoV, Aboagye et al [ 158 ] showed that virus nucleocapsid causes an overexpression of antiviral genes, namely, TNF, IL6, IL8, and CXCL10, whose expression is stable over time. The pathogenesis of SARS-CoV-2 damage is still unknown, but unlike other SARS, SARS-CoV-2 shows an initial increase of the Th2 cytokines IL-4 and IL-10 which suppress inflammation [ 51 ] and balance the Th1 hyper-response.…”

Section: Sars-cov-2: Inflammation and Lung Diseasementioning

confidence: 99%

Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment

Cicco

Racanelli

et al. 2020

Mediators of Inflammation

149

148

View full text Add to dashboard Cite

COVID-19 is a pandemic disease caused by the new coronavirus SARS-CoV-2 that mostly affects the respiratory system. The consequent inflammation is not able to clear viruses. The persistent excessive inflammatory response can build up a clinical picture that is very difficult to manage and potentially fatal. Modulating the immune response plays a key role in fighting the disease. One of the main defence systems is the activation of neutrophils that release neutrophil extracellular traps (NETs) under the stimulus of autophagy. Various molecules can induce NETosis and autophagy; some potent activators are damage-associated molecular patterns (DAMPs) and, in particular, the high-mobility group box 1 (HMGB1). This molecule is released by damaged lung cells and can induce a robust innate immunity response. The increase in HMGB1 and NETosis could lead to sustained inflammation due to SARS-CoV-2 infection. Therefore, blocking these molecules might be useful in COVID-19 treatment and should be further studied in the context of targeted therapy.

show abstract

“…Furthermore, several reports suggest that the severe acute respiratory syndrome coronavirus (SARS-CoV) N protein functions as an immune evasion protein and an antagonist of the host interferon response [35,36,37]. Recently, the overexpression of MERS-CoV N in human A549 cells was found to be linked to an up-regulation of antiviral host gene expression including the synthesis of the inflammatory chemokine CXCL10 [38]. Despite this possible immune modulatory activity, SARS-CoV N-specific immune responses are reported to be long-lived and more broadly reactive when compared to SARS-CoV S-specific immunity [39].…”

Section: Introductionmentioning

confidence: 99%

CD8+ T Cells Responding to the Middle East Respiratory Syndrome Coronavirus Nucleocapsid Protein Delivered by Vaccinia Virus MVA in Mice

Veit¹,

Jany²,

Fux³

et al. 2018

Viruses

View full text Add to dashboard Cite

Middle East respiratory syndrome coronavirus (MERS-CoV), a novel infectious agent causing severe respiratory disease and death in humans, was first described in 2012. Antibodies directed against the MERS-CoV spike (S) protein are thought to play a major role in controlling MERS-CoV infection and in mediating vaccine-induced protective immunity. In contrast, relatively little is known about the role of T cell responses and the antigenic targets of MERS-CoV that are recognized by CD8+ T cells. In this study, the highly conserved MERS-CoV nucleocapsid (N) protein served as a target immunogen to elicit MERS-CoV-specific cellular immune responses. Modified Vaccinia virus Ankara (MVA), a safety-tested strain of vaccinia virus for preclinical and clinical vaccine research, was used for generating MVA-MERS-N expressing recombinant N protein. Overlapping peptides spanning the whole MERS-CoV N polypeptide were used to identify major histocompatibility complex class I/II-restricted T cell responses in BALB/c mice immunized with MVA-MERS-N. We have identified a H2-d restricted decamer peptide epitope in the MERS-N protein with CD8+ T cell antigenicity. The identification of this epitope, and the availability of the MVA-MERS-N candidate vaccine, will help to evaluate MERS-N-specific immune responses and the potential immune correlates of vaccine-mediated protection in the appropriate murine models of MERS-CoV infection.

show abstract

Overexpression of the nucleocapsid protein of Middle East respiratory syndrome coronavirus up-regulates CXCL10

Cited by 16 publications

References 23 publications

Direct activation of endothelial cells by SARS-CoV-2 nucleocapsid protein is blocked by Simvastatin

Direct activation of endothelial cells by SARS-CoV-2 nucleocapsid protein is blocked by Simvastatin

Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment

CD8+ T Cells Responding to the Middle East Respiratory Syndrome Coronavirus Nucleocapsid Protein Delivered by Vaccinia Virus MVA in Mice

Contact Info

Product

Resources

About