
This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Aop: 430
Title
Sars-CoV-2 Interferon-I antiviral response antagonism and increased viral production leading to viral infection proliferation
Short name
Graphical Representation
Point of Contact
Contributors
- Sally Mayasich
- Arthur Author
Status
Author status | OECD status | OECD project | SAAOP status |
---|---|---|---|
Under development: Not open for comment. Do not cite | Under Development | 1.96 | Included in OECD Work Plan |
This AOP was last modified on May 08, 2022 11:33
Revision dates for related pages
Page | Revision Date/Time |
---|---|
ACE2 binding to viral S-protein | November 24, 2021 05:41 |
Increased susceptibility to viral entry | April 27, 2021 19:46 |
Interferon-I antiviral response, antagonized | July 09, 2021 16:32 |
Increased coronavirus production | April 20, 2021 00:54 |
Viral infection and host-to-host transmission, proliferated | October 24, 2021 15:55 |
ACE2 binding to viral S-protein leads to Increased susceptibility to viral entry | March 02, 2020 03:19 |
Increased susceptibility to viral entry leads to IFN-I response, antagonized | October 24, 2021 17:10 |
IFN-I response, antagonized leads to Increased SARS-CoV-2 production | October 24, 2021 17:11 |
Increased SARS-CoV-2 production leads to Viral infection, proliferated | October 24, 2021 17:12 |
SARS-CoV | March 01, 2020 10:42 |
Sars-CoV-2 | February 23, 2021 04:50 |
HCoV-NL63 | February 07, 2021 07:01 |
Abstract
SARS and SARS-CoV-2 coronoviruses enter the cell through interaction with the ACE2 receptor. The first event upon cell entry after uncoating is the primary translation of the ORF1a and ORF1b genomic RNA to produce non-structural proteins (nsps). The nsps structural proteins, and accessory proteins , are encoded by 10 ORFs in the SARS-CoV-2 RNA genome. They may have multiple functions during viral replication as well as in evasion of the host innate immune response, thus augmenting viral replication and spread. The early innate immune system evasion proteins produced in the sub-genomic translation after viral genome replication and transcription within the infected cell suppress the Interferon-I antiviral response to increase viral load. Beyond potentially contributing to the severity of clinical symptoms and adverse disease outcome in individuals, increase in viral load can lead to proliferation from person-to-person and across species, also increasing the likelihood of mutations that result in more infective or virulant strains.
Background (optional)
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Sequence | Type | Event ID | Title | Short name |
---|
1 | MIE | 1739 | ACE2 binding to viral S-protein | ACE2 binding to viral S-protein |
2 | KE | 1738 | Increased susceptibility to viral entry | Increased susceptibility to viral entry |
3 | KE | 1901 | Interferon-I antiviral response, antagonized | IFN-I response, antagonized |
4 | KE | 1847 | Increased coronavirus production | Increased SARS-CoV-2 production |
5 | AO | 1939 | Viral infection and host-to-host transmission, proliferated | Viral infection, proliferated |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
---|
ACE2 binding to viral S-protein leads to Increased susceptibility to viral entry | adjacent | High | Moderate |
Increased susceptibility to viral entry leads to IFN-I response, antagonized | adjacent | High | Not Specified |
IFN-I response, antagonized leads to Increased SARS-CoV-2 production | adjacent | High | Not Specified |
Increased SARS-CoV-2 production leads to Viral infection, proliferated | adjacent | High | Not Specified |
Network View
Stressors
Name | Evidence Term |
---|---|
SARS-CoV | High |
Sars-CoV-2 | High |
HCoV-NL63 | High |
Life Stage Applicability
Life stage | Evidence |
---|---|
All life stages | High |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
---|---|---|---|
mammals | mammals | High | NCBI |
Sex Applicability
Sex | Evidence |
---|---|
Unspecific | Not Specified |