General Overview
Coronaviruses cause acute and chronic respiratory, enteric, and central nervous system (CNS) diseases in humans and many species of animals. Coronaviruses are divided into three groups based on the genome sequences, including SARS-CoV (a member of group II) as well as murine hepatitis virus (MHV), bovine coronavirus, porcine hemagglutinating encephalomyelitis virus (HEV), equine coronavirus, and human coronavirues OC43 and NL63, which also cause respiratory infections. SARS-CoV, the causal pathogen of severe acute respiratory syndrome (SARS), caused a large outbreak of this severe pneumonia occurred in Hong Kong in 2003 and rapidly spread throughout the world. SARS-CoV can infect and replicate in mice, ferrets, hamsters, cats, and several species of nonhuman primates (cynomolgus and rhesus macaques, African green monkeys, and marmosets). MHV that infects both mice and rats often has been studied as a suitable model of human coronavirus diseases, according to Watanabe et al.[1].
Summary Data
DeDiego et al.[2] challenged four groups of the transgenic mice intranasally with graded doses of rSARS-CoV and the survival was monitored for 13 days.
De Albuquerque et al.[3] inoculated A/J mice with MHV-1 intranasally via intranasal route and monitored the survival for 21 days.
Summary
By increasing the number of data points, the pooling narrows the range of the confidence region of the parameter estimates and enhances the statistical precision.
ID | # of Doses | Agent Strain | Dose Units | Host type | Μodel | Optimized parameters | Response type | Reference |
---|---|---|---|---|---|---|---|---|
260 | 4 | rSARS-CoV | PFU | mice hACE-2 | exponential |
k = 2.97E-03 LD50/ID50 = 2.33E+02 |
death |
DeDiego et al.[2] |
260, 261 | 8 | rSARS-CoV | PFU | mice hACE-2 and A/J | exponential |
k = 2.46E-03 LD50/ID50 = 2.82E+02 |
death | |
261 | 4 | MHV-1 | PFU | A/J mice | exponential |
k = 2.14E-03 LD50/ID50 = 3.24E+02 |
death | De Albuquerque et al.[3] |
Optimization Output for Exp. 260:
Experiment ID: 260
# of Doses: 4
Agent Strain: rSARS-CoV
Dose Units: PFU
Host type: mice hACE-2
Μodel: exponential
Optimized parameters:
k = 2.97E-03
LD50/ID50 = 2.33E+02
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Optimization Output for Exp. 260, 261:
Best Fit
Experiment ID: 260, 261
# of Doses: 8
Agent Strain: rSARS-CoV
Dose Units: PFU
Host type: mice hACE-2 and A/J
Μodel: exponential
Optimized parameters:
k = 2.46E-03
LD50/ID50 = 2.82E+02
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Optimization Output for Exp. 261:
Experiment ID: 261
# of Doses: 4
Agent Strain: MHV-1
Dose Units: PFU
Host type: A/J mice
Μodel: exponential
Optimized parameters:
k = 2.14E-03
LD50/ID50 = 3.24E+02
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Parameter histogram for exponential model (uncertainty of the parameter)
Exponential model plot, with confidence bounds around optimized model
Recommended Model
It is recommended that the pooled experiments 260 and 261 should be used as the best dose-response model. Both strains are common in outbreaks. The pooling narrows the range of the confidence region of the parameter estimates and enhances the statistical precision.
References
- Development of a Dose-Response Model for SARS Coronavirus, , Risk Analysis: An International Journal, 07/2010, Volume 30, Issue 7, p.1129–1138, (2010)
- Pathogenicity of severe acute respiratory coronavirus deletion mutants in hACE-2 transgenic mice, , Virology., Volume 376, p.2, (2008)
- Murine Hepatitis Virus Strain 1 Produces a Clinically Relevant Model of Severe Acute Respiratory Syndrome in A/J Mice, , Journal of Virology, Volume 80, p.21, (2006)
ID | # of Doses | Agent Strain | Dose Units | Host type | Μodel | Optimized parameters | Response type | Reference |
---|---|---|---|---|---|---|---|---|
260 | 4 | rSARS-CoV | PFU | mice hACE-2 | exponential |
k = 2.97E-03 LD50/ID50 = 2.33E+02 |
death | Murine Hepatitis Virus Strain 1 Produces a Clinically Relevant Model of Severe Acute Respiratory Syndrome in A/J Mice." Journal of Virology. 80 (2006): 21. | "
260, 261 | 0 | rSARS-CoV | PFU | mice hACE-2 and A/J | exponential |
k = 2.46E-03 LD50/ID50 = 2.82E+02 |
death | |
261 | 4 | MHV-1 | PFU | A/J mice | exponential |
k = 2.14E-03 LD50/ID50 = 3.24E+02 |
death | Murine Hepatitis Virus Strain 1 Produces a Clinically Relevant Model of Severe Acute Respiratory Syndrome in A/J Mice." Journal of Virology. 80 (2006): 21. | "
k = 2.97E-03
LD50/ID50 = 2.33E+02
|
|
|
Parameter histogram for exponential model (uncertainty of the parameter)
Exponential model plot, with confidence bounds around optimized model
k = 2.46E-03
LD50/ID50 = 2.82E+02
|
|
|
Parameter histogram for exponential model (uncertainty of the parameter)
Exponential model plot, with confidence bounds around optimized model
k = 2.14E-03
LD50/ID50 = 3.24E+02
|
|
|
Parameter histogram for exponential model (uncertainty of the parameter)
Exponential model plot, with confidence bounds around optimized model