To the extent possible under law, AOP-Wiki has waived all copyright and related or neighboring rights to KE:1939

Event: 1939

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Viral infection and host-to-host transmission, proliferated

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Viral infection, proliferated
Explore in a Third Party Tool

Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Individual

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
viral release from host cell increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE. Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
SARS-CoV-2 leads to infection proliferation AdverseOutcome Sally Mayasich (send email) Under development: Not open for comment. Do not cite Under Development

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
human Homo sapiens High NCBI
mink Mustela lutreola High NCBI
cat Felis catus High NCBI
rhesus macaque Macaca mulatta High NCBI
dog Canis lupus familiaris Moderate NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
All life stages High

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Unspecific High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Much is now understood in terms of human-to-human COVID-19 transmission. Coronaviruses, as with many other respiratory viruses, are transmitted primarily through respiratory droplets, but can also spread through aerosols, fecal-oral transmission, or contact with contaminated surfaces (Harrison et al. 2020). Respiratory droplets and aerosols containing the virus are generated through an infected person coughing, sneezing or talking, and enter the secondary host system through upper and lower respiratory tissues, with the lung being the primary tropism. Barriers to transmission in place worldwide include social distancing, face shields, cloth masks, frequent hand washing, and surface disinfection (Harrison et al. 2020).

Vaccination is the standard strategy for reducing or eliminating viral disease transmission, symptoms, and mortality in humans, and in some cases domesticated animals. However, the weight of evidence indicates that the reservoir species (bats in the case of betacoronaviruses) and potential intermediate hosts are wildlife, and different control measures will be required to prevent future spillover. Indeed, the intermediate host of the SARS-CoV-2 virus has yet to be identified (Delahay et al. 2021). This key event is therefore focused primarily on the species of potential concern, exposure and transmission routes across species, and the conditions indicative of or conducive toward cross-species spillover of zoonoses or infectious viral diseases of animal origin.

Species of Potential Concern

The reservoir host for SARS-CoV-2-like viruses is believed to be the bat.

Exposure and Transmission Routes

SARS-CoV-2-infected media (respiratory droplets, bodily fluids, tissues, feces): Exposure routes are the pathway into the body of the virus shed from an infected reservoir host animal to the intermediate host, or either type of host animal to humans. These routes may include inhalation, oral, or through broken skin or mucosal membranes (e.g., eyes, nostrils) after touching contaminated media or surfaces and then touching the face (Harrison et al. 2020). Animals may transfer saliva or nasal discharge directly through facial contact, licking or biting. Transmission occurs through these routes when the virus reaches a tissue with cells that allow entry and replication.

Spillover Conditions

Conditions that allow for exposure and transmission across species:

  • Close proximity of animal communities (bats to potential intermediate hosts; wildlife to domestic animal farms).
  • Direct human contact with wildlife (Johnson et al. 2015), including:
    • Zoos, wildlife farms, domesticated animal farms, feeding and animal care;
    • Hunting and dressing wild game;
    • Cleaning of storage buildings, barns, or other structures that may be used by wildlife for shelter, breeding, or feeding, with potential for feces or other contamination (CDC, 2021);
    • Wet markets where live animals or bush meat are traded;
    • Research facilities that express viruses from wild samples in cell culture, that house potential host species, or that collect and store bodily fluid or tissue samples.
  • Virus isolated from animal species shows genomic similarity to the human virus, but also high host plasticity to be capable of cross-species viral immune evasion and replication (Johnson et al. 2015).

Similar host genetics. Spillover species and new host species share genetic similarity in the components of the cell entry, immune system and replication machinery (Warren et al. 2019). That is, the virus can enter the cell and evade the virus detection and immediate systemic type I interferon (IFN) response to allow replication and generation of viral load in both species. The viral proteins must be capable of interacting with the appropriate cellular proteins in either species. The most studied and considered indicative of infectability is the ACE2 and other cell entry proteins.

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Either the virus or antibodies can be detected with available tests. Active infection can be detected through PCR tests from nasal swab, oropharyngeal swab, rectal swab or saliva samples that indicate the quantity and/or presence of the virus. Antibodies can be detected in blood using various assays including immunofluorescence.

ELISA, Indirect immunofluorescence assay (IIFA) for antibodies (Schlottau et al. 2020; Freuling et al. 2020)

Virus neutralization test (VNT) for antibodies (Schlottau et al. 2020; Freuling et al. 2020)

Quantitative reverse transcription PCR (qRT-PCR) for viral load (log10 genome copies) (Freuling et al. 2020)

Titration (Tissue culture infectious dose where 50% of infected cells display cytopathic effect [TCID50 assay]: levels of infectious virus, or viral titre) (Freuling et al. 2020)

Virus-specific immunoglobulin characterization (Freuling et al. 2020)

SARS-CoV-2 spike protein neutralizing antibodies in saliva from animals that developed serum antibodies (Freuling et al. 2020)

Serum sample, autopsy, histopathology for tissue lesions (Schlottau et al. 2020; Freuling et al. 2020)

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Homo sapiens

Broad mammalian host range based on spike protein tropism for and binding to ACE2 (Conceicao et al. 2020; Wu et al. 2020) and cross-species ACE2 structural analysis (Damas et al. 2020). Some literature found on non-human hosts indicates that NSPs and accessory proteins can interact in a similar manner with bird (chicken) and other mammal proteins in the IFN-I pathway (Moustaqil et al. 2021; Rui et al. 2021).

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

References

List of the literature that was cited for this KE description. More help

Under construction

Freuling CM, Breithaupt A, Müller T, et al. 2020. Susceptibility of Raccoon Dogs for Experimental SARS-CoV-2 Infection. Emerging Infectious Diseases. 26(12):2982-2985. doi:10.3201/eid2612.203733.

CDC, 2021. https://www.cdc.gov/hantavirus/hps/transmission.html

Conceicao et al. 2020. The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins. PLoS Biol 18(12): e3001016. https://doi.org/10.1371/journal.pbio.3001016

Damas et al. 2020. Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates. PNAS vol. 117 no. 36:22311–22322 www.pnas.org/cgi/doi/10.1073/pnas.2010146117 

Moustaqil et al. 2021. SARS-CoV-2 proteases PLpro and 3CLpro cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species, Emerging Microbes & Infections, 10:1, 178-195. https://doi.org/10.1080/22221751.2020.1870414

Rui et al. 2021. Unique and complementary suppression of cGAS-STING and RNA sensing-triggered innate immune responses by SARS-CoV-2 proteins. Sig Transduct Target Ther 6, 123. https://doi.org/10.1038/s41392-021-00515-5

Wu et al. 2020. Broad host range of SARS-CoV-2 and the molecular basis for SARS-CoV-2 binding to cat ACE2. Cell Discovery 6:68. https://doi.org/10.1038/s41421-020-00210-9