SARS-CoV-2, the causative agent of the coronavirus disease 2019 (COVID-19), has resulted in more than 3.8 million deaths worldwide. The innate immune system serves as the first line in defending the host from viral infection. However, viruses have evolved sophisticated approaches to impede antiviral innate immunity. Viral proteins encoded by the SARS-CoV-2 genome are deeply involved in the regulation of innate immune signaling activation. NSP1, NSP12, ORF6, and M protein of SARS-CoV-2 were found to inhibit MDA5 dependent type I interferon induction. However, the existence of HLA-I peptides from out-of-frame SARS-CoV-2 proteins indicated an unrecognized virus-protein interaction mechanism.
On the other hand, the angiotensin-converting enzyme 2 (ACE2) has been identified as the main receptor for Spike protein-mediated SARS-CoV-2 infection in respiratory epithelial cells. However, in SARS-CoV-2 infected myeloid cells such as monocytes and alveolar macrophages, barely any expression of ACE2 was detected, which indicated an alternative infection mediator in these immune cells. Meanwhile, cytokine storm and subsequent multi-organ failure caused by the imbalanced immune responses were considered as the main lethality contributor of SARS-CoV-2 infection. Thus, how SARS-CoV-2 infection disrupts the innate immune system, characteristics and outcomes of SARS-CoV-2 infecting immune cells, and methods to interrupt infection of SARS-CoV-2 on immune cells remain further investigation.
This Research Topic is focused on uncovering the uncharacterized mechanism of the involvement of SARS-CoV-2 viral proteins in antiviral innate immune signaling activation (both the canonical viral proteins and the novel out-of-frame viral proteins) and finding membrane-localized proteins that mediate SARS-CoV-2 infection in immune cells (monocytes, macrophages, etc.), which may serve as druggable targets for the treatment of coronavirus infection-induced hyperinflammation.
The submissions can cover but are not limited to the following:
• Influences of canonical viral proteins and out-of-frame Spike and Nucleocapsid protein on innate immunity and the mechanism underlies;
• Discovery of novel receptors on immune cells that mediate or help on the entry of SARS-CoV-2;
• Unveil potential druggable targets (membrane-localized proteins) to help to inhibit SARS-CoV-2 infection of immune cells;
• Identify potential drugs to stabilize the coronavirus infection-induced excessive inflammation;
• Discovery of inhibitors (drugs) that block the coronavirus infection-induced cell death and syncytia formation of infected cells.
SARS-CoV-2, the causative agent of the coronavirus disease 2019 (COVID-19), has resulted in more than 3.8 million deaths worldwide. The innate immune system serves as the first line in defending the host from viral infection. However, viruses have evolved sophisticated approaches to impede antiviral innate immunity. Viral proteins encoded by the SARS-CoV-2 genome are deeply involved in the regulation of innate immune signaling activation. NSP1, NSP12, ORF6, and M protein of SARS-CoV-2 were found to inhibit MDA5 dependent type I interferon induction. However, the existence of HLA-I peptides from out-of-frame SARS-CoV-2 proteins indicated an unrecognized virus-protein interaction mechanism.
On the other hand, the angiotensin-converting enzyme 2 (ACE2) has been identified as the main receptor for Spike protein-mediated SARS-CoV-2 infection in respiratory epithelial cells. However, in SARS-CoV-2 infected myeloid cells such as monocytes and alveolar macrophages, barely any expression of ACE2 was detected, which indicated an alternative infection mediator in these immune cells. Meanwhile, cytokine storm and subsequent multi-organ failure caused by the imbalanced immune responses were considered as the main lethality contributor of SARS-CoV-2 infection. Thus, how SARS-CoV-2 infection disrupts the innate immune system, characteristics and outcomes of SARS-CoV-2 infecting immune cells, and methods to interrupt infection of SARS-CoV-2 on immune cells remain further investigation.
This Research Topic is focused on uncovering the uncharacterized mechanism of the involvement of SARS-CoV-2 viral proteins in antiviral innate immune signaling activation (both the canonical viral proteins and the novel out-of-frame viral proteins) and finding membrane-localized proteins that mediate SARS-CoV-2 infection in immune cells (monocytes, macrophages, etc.), which may serve as druggable targets for the treatment of coronavirus infection-induced hyperinflammation.
The submissions can cover but are not limited to the following:
• Influences of canonical viral proteins and out-of-frame Spike and Nucleocapsid protein on innate immunity and the mechanism underlies;
• Discovery of novel receptors on immune cells that mediate or help on the entry of SARS-CoV-2;
• Unveil potential druggable targets (membrane-localized proteins) to help to inhibit SARS-CoV-2 infection of immune cells;
• Identify potential drugs to stabilize the coronavirus infection-induced excessive inflammation;
• Discovery of inhibitors (drugs) that block the coronavirus infection-induced cell death and syncytia formation of infected cells.