TY - JOUR
T1 - Looking for pathways related to COVID-19: confirmation of pathogenic mechanisms by SARS-CoV-2–host interactome
AU - Messina, Francesco
AU - Giombini, Emanuela
AU - Montaldo, Chiara
AU - Sharma, Ashish Arunkumar
AU - Zoccoli, Antonio
AU - Sekaly, Rafick-Pierre
AU - Locatelli, Franco
AU - Zumla, Alimuddin
AU - Maeurer, Markus
AU - Capobianchi, Maria R.
AU - Lauria, Francesco Nicola
AU - Ippolito, Giuseppe
PY - 2021
Y1 - 2021
N2 - In the last months, many studies have clearly described several mechanisms of SARS-CoV-2 infection at cell and tissue level, but the mechanisms of interaction between host and SARS-CoV-2, determining the grade of COVID-19 severity, are still unknown. We provide a network analysis on protein–protein interactions (PPI) between viral and host proteins to better identify host biological responses, induced by both whole proteome of SARS-CoV-2 and specific viral proteins. A host-virus interactome was inferred, applying an explorative algorithm (Random Walk with Restart, RWR) triggered by 28 proteins of SARS-CoV-2. The analysis of PPI allowed to estimate the distribution of SARS-CoV-2 proteins in the host cell. Interactome built around one single viral protein allowed to define a different response, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. Finally, the network-based approach highlighted a possible direct action of ORF3a and NS7b to enhancing Bradykinin Storm. This network-based representation of SARS-CoV-2 infection could be a framework for pathogenic evaluation of specific clinical outcomes. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients.
AB - In the last months, many studies have clearly described several mechanisms of SARS-CoV-2 infection at cell and tissue level, but the mechanisms of interaction between host and SARS-CoV-2, determining the grade of COVID-19 severity, are still unknown. We provide a network analysis on protein–protein interactions (PPI) between viral and host proteins to better identify host biological responses, induced by both whole proteome of SARS-CoV-2 and specific viral proteins. A host-virus interactome was inferred, applying an explorative algorithm (Random Walk with Restart, RWR) triggered by 28 proteins of SARS-CoV-2. The analysis of PPI allowed to estimate the distribution of SARS-CoV-2 proteins in the host cell. Interactome built around one single viral protein allowed to define a different response, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. Finally, the network-based approach highlighted a possible direct action of ORF3a and NS7b to enhancing Bradykinin Storm. This network-based representation of SARS-CoV-2 infection could be a framework for pathogenic evaluation of specific clinical outcomes. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients.
KW - SARS-COV-3
KW - SARS-COV-3
UR - http://hdl.handle.net/10807/228817
U2 - 10.1038/s41419-021-03881-8
DO - 10.1038/s41419-021-03881-8
M3 - Article
SN - 2041-4889
VL - 12
SP - 1
EP - 10
JO - CELL DEATH & DISEASE
JF - CELL DEATH & DISEASE
ER -
