Exosomal microRNAs Drive Thrombosis in COVID-19

Gambardella, Jessica; Sardu, Celestino; Morelli, Marco Bruno; Messina, Vito; Castellanos, Vanessa; Marfella, Raffaele; Maggi, Paolo; Paolisso, Giuseppe; Wang, Xujun; Santulli, Gaetano

doi:10.1101/2020.06.16.20133256

Cited by 17 publications

(18 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We did not identify viral proteins via the purification of exosomes; thus, we can conclude that viral particles were not purified together with exosomes, suggesting that the RNA material was originally present in the cargo. A very recent study showed that exosomal microRNAs may drive thrombosis in COVID-19 patients ( Gambardella et al, 2020 ) while Song and colleagues found that GM3-enriched exosomes positively correlated with disease severity, suggesting that they may participate in the pathological processes associated with COVID-19 progression ( Song et al, 2020 ). Moreover, exosome-based strategies were also proposed to treat COVID-19 ( Hassanpour et al, 2020 ) or prevent SARS-CoV-2 infection ( Cocozza et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection

Barberis

Vanella

Falasca

et al. 2021

Front. Mol. Biosci.

172

188

View full text Add to dashboard Cite

Knowledge of the host response to the novel coronavirus SARS-CoV-2 remains limited, hindering the understanding of COVID-19 pathogenesis and the development of therapeutic strategies. During the course of a viral infection, host cells release exosomes and other extracellular vesicles carrying viral and host components that can modulate the immune response. The present study used a shotgun proteomic approach to map the host circulating exosomes’ response to SARS-CoV-2 infection. We investigated how SARS-CoV-2 infection modulates exosome content, exosomes’ involvement in disease progression, and the potential use of plasma exosomes as biomarkers of disease severity. A proteomic analysis of patient-derived exosomes identified several molecules involved in the immune response, inflammation, and activation of the coagulation and complement pathways, which are the main mechanisms of COVID-19–associated tissue damage and multiple organ dysfunctions. In addition, several potential biomarkers—such as fibrinogen, fibronectin, complement C1r subcomponent and serum amyloid P-component—were shown to have a diagnostic feature presenting an area under the curve (AUC) of almost 1. Proteins correlating with disease severity were also detected. Moreover, for the first time, we identified the presence of SARS-CoV-2 RNA in the exosomal cargo, which suggests that the virus might use the endocytosis route to spread infection. Our findings indicate circulating exosomes’ significant contribution to several processes—such as inflammation, coagulation, and immunomodulation—during SARS-CoV-2 infection. The study’s data are available via ProteomeXchange with the identifier PXD021144.

show abstract

Section: Discussionmentioning

confidence: 99%

Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection

Barberis

Vanella

Falasca

et al. 2021

Front. Mol. Biosci.

172

188

View full text Add to dashboard Cite

show abstract

“…The SARS-CoV-2 genes encode multiple structural and accessory proteins that facilitate viral entry and invasion of host cells [13], and are involved in inflammasome activation, cell death, and humoral immune response [14,15]. Recent clinical and computational studies on coronavirus disease 2019 (COVID- 19) have shown the presence of both virus and host miRNAs with potentially significant roles in disease pathogenesis [16][17][18], including cases of thrombosis [19]. Here, we identified novel v-miRNAs in SARS-CoV-2-infected cell lines by small RNA deep sequencing and validated their expression in patient specimens using reverse transcription (RT) and droplet-digital PCR (ddPCR).…”

Section: Introductionmentioning

confidence: 99%

Viral MicroRNAs Encoded by Nucleocapsid Gene of SARS-CoV-2 Are Detected during Infection, and Targeting Metabolic Pathways in Host Cells

Meng

Siu

Mok

et al. 2021

Cells

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are critical regulators of gene expression that may be used to identify the pathological pathways influenced by disease and cellular interactions. Viral miRNAs (v-miRNAs) encoded by both DNA and RNA viruses induce immune dysregulation, virus production, and disease pathogenesis. Given the absence of effective treatment and the prevalence of highly infective SARS-CoV-2 strains, improved understanding of viral-associated miRNAs could provide novel mechanistic insights into the pathogenesis of COVID-19. In this study, SARS-CoV-2 v-miRNAs were identified by deep sequencing in infected Calu-3 and Vero E6 cell lines. Among the ~0.1% small RNA sequences mapped to the SARS-CoV-2 genome, the top ten SARS-CoV-2 v-miRNAs (including three encoded by the N gene; v-miRNA-N) were selected. After initial screening of conserved v-miRNA-N-28612, which was identified in both SARS-CoV and SARS-CoV-2, its expression was shown to be positively associated with viral load in COVID-19 patients. Further in silico analysis and synthetic-mimic transfection of validated SARS-CoV-2 v-miRNAs revealed novel functional targets and associations with mechanisms of cellular metabolism and biosynthesis. Our findings support the development of v-miRNA-based biomarkers and therapeutic strategies based on improved understanding of the pathophysiology of COVID-19.

show abstract

“…miRNAs regulate several diseases, such as cancers, diabetes, and cardiovascular disease, by regulating the expression of target genes ( Barwari et al, 2016 ; Cao et al, 2020 ; Chakraborty et al, 2014 ; Chen et al, 2020d ; Liang and Li, 2020 ; Reddy, 2015 ). Moreover, recent studies have identified the association of miRNAs with antiviral effects by targeting both the 3’UTR and coding region of the viral genome ( Gambardella et al, 2020 ; Guterres et al, 2020 ; Ivashchenko et al, 2020 ; Song et al, 2010 ; Wang et al, 2012 ). One study identified several miRNAs that interact with SARS-CoV, MERS-CoV, and SARS-CoV-2 viral genomes ( Ivashchenko et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Expression Analyses of MicroRNAs in Hamster Lung Tissues Infected by SARS-CoV-2

Kim

Park

Kang

et al. 2020

Molecules and Cells

View full text Add to dashboard Cite

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an infectious disease with multiple severe symptoms, such as fever over 37.5°C, cough, dyspnea, and pneumonia. In our research, microRNAs (miRNAs) binding to the genome sequences of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory-related coronavirus (MERS-CoV), and SARS-CoV-2 were identified by bioinformatic tools. Five miRNAs (hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-16-5p, and hsa-miR-196a-1-3p) were found to commonly bind to SARS-CoV, MERS-CoV, and SARS-CoV-2. We also identified miRNAs that bind to receptor proteins, such as ACE2, ADAM17, and TMPRSS2, which are important for understanding the infection mechanism of SARS-CoV-2. The expression patterns of those miRNAs were examined in hamster lung samples infected by SARS-CoV-2. Five miRNAs (hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-221-3p, hsa-miR-140-3p, and hsa-miR-422a) showed differential expression patterns in lung tissues before and after infection. Especially, hsa-miR-15b-5p and hsa-miR-195-5p showed a large difference in expression, indicating that they may potentially be diagnostic biomarkers for SARS-CoV-2 infection.

show abstract

Exosomal microRNAs Drive Thrombosis in COVID-19

Cited by 17 publications

References 14 publications

Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection

Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection

Viral MicroRNAs Encoded by Nucleocapsid Gene of SARS-CoV-2 Are Detected during Infection, and Targeting Metabolic Pathways in Host Cells

Expression Analyses of MicroRNAs in Hamster Lung Tissues Infected by SARS-CoV-2

Contact Info

Product

Resources

About