Table 2.
Animal models of SARS-CoV.
| Sr. No | Animal model | Disease induction (strain & route) | Clinical signs | Advantages | Disadvantages | References |
|---|---|---|---|---|---|---|
| 1 | Rhesus macaques | SARS-CoV, Tor2, 107 PFU, IV/IT | Significant viral titer in the lungs | Useful for therapeutic evaluation and vaccines immunogenicity | In SARS study limited use | Rowe et al. (2004) |
| 2 | Rhesus macaques | SARS-CoV, Urbani, 106 PFU, IT/ IN | Could not show any clinical sign | Used for Therapeutic evaluation and vaccines immunogenicity | Clinical illness was not present | McAuliffea et al. (2004) |
| 3 | Rhesus macaques | SARS-CoV, PUMC01, 105 PFU, IN | Pulmonary changes were observed on 5–60 dpi; All macaques reported fever 2–3 dpi | Immunological and pathological similarity with clinical condition | The symptoms are less severe as comparison of clinical scenario | Qin et al. (2005) |
| 4 | Cynomolgus monkeys | SARS-CoV, 103 and 106 TCID50, IN/IT | Interstitial pneumonia, alveolar macrophages and neutrophils, diffuse alveolar damage | Helpful for the study of SARS pathogenesis and can be used for therapeutic and vaccine studies | Availability and cost | Fouchier et al. (2003) |
| 5 | Cynomolgus monkeys | SARS-CoV, 1 × 106 TCID50, IT/ IN, | Symptoms appeared as difficulty in respiration; more diffuse alveolar damage, type 2 pneumocyte hyperplasia and alveolar macrophages are present in alveolar lumina | Useful for vaccine and therapeutic drug evaluation | There is issue with availability, housing cost; early clearance of virus and pneumonitis occurred | Kuiken et al. (2003) |
| 6 | Cynomolgus monkeys | SARS-CoV, Tor2, 107 PFU, IT | Mild cough; a few scattered pleural adhesions | Presentation of critical disease | Symptoms cleared quickly and animals becomes asymptomatic from 8 to 10 days | Rowe et al. (2004) |
| 7 | Cynomolgus monkeys | SARS-CoV, Urbani, 3 × 106.3 PFU, IB/ IN, | Reported nasal congestion, mild respiration distress; animals become lethargic; pulmonary related disease | Helpful in immunogenicity of vaccines and therapeutics studies | Lack of apparent clinical illness | McAuliffe et al. (2004) |
| 8 | African green monkey | SARS-CoV, Urbani, 106.3 TCID50, IB /IN, | Virologic data and histopathologic findings, focal interstitial pneumonitis was noticed in some African green monkey | Useful for evaluation of vaccine efficacy against infection | Rapid clearance of virus and pneumonitis in African green monkey | McAuliffe et al. (2004) |
| 9 | Marmoset | SARS-CoV, Urbani, 106 PFU, IT | Marmoset reported there is elevation of temperature, interstitial pneumonitis, multifocal lymphocytic hepatitis and diffuse interstitial colitis | Can be used in Pathogenesis, therapeutics and vaccine efficacy studies | This model is not able to explain the viral antigen/viral RNA within hepatic tissues | Greenough et al. (2005) |
| 10 | BALB/c mice |
4–6 week aged SARS-CoV, Urbani, 105 TCID50, IN |
High viral load in respiratory tract | Useful for immunological studies | No overt clinical sign was present | Subbarao et al. (2004) |
| 11 | BALB/c mice | 12–14 month aged SARS-CoV, Urbani, 105 TCID50, IN | Old aged mice observed significant loss of weight, mild dehydration and alveolar damage; Also reported intra-alveolar edema, perivascular infiltrates | Useful for vaccine evaluation | There is need of further characterization and immune senescence | Vogel et al. (2007) |
| 12 | 129SvEv /STAT 1-/- mice | SARS-CoV, Tor2, 6 × 106 PFU/30 µL, IN | Viral replication, morbidity, mortality and pneumonitis | STAT 1-/- exhibited innate immunity | Defect in innate immunity | Hogan et al. (2004) |
| 13 | 129SvEv /STAT 1-/- mice | SARS-CoV, Urbani, 105 PFU, IN | Reported severity of disease in this study, high virus replication and severe pulmonary lesions | Viral replication, histopathology similar to clinical conditions | Lack of a normal innate immune did not enhance virus pathogenesis | Frieman et al. (2010) |
| 14 | C57BL/6 mice | SARS-CoV, Urbani 1 × 104 TCID50, IN | Virus infected the respiratory tract (bronchial and bronchiolar epithelium); failure to thrive and also observed infection reached to the brain | Useful for immunological studies | Fail to show clinical signs of disease | Glass et al. (2004) |
| 15 | Transgenic hACE2 mice | SARS-CoV, PUMC01 105 TCID50, IN | Transgenic mice showed severe lung damage, systemic inflammatory reactions, degeneration, and necrosis in many extra-pulmonary organs | More susceptible to infection as comparison to wild type mice, and more closely resemblance to human pathology of SARS | Tissue distribution was limited, decreased expression of hACE2 and lack of lethality | Yang et al. (2007) |
| 16 | Golden Syrian hamster | 5-week aged, SARS-CoV, Urbani, 103TCID50, IN | Increased viral replication in lungs, related interstitial pneumonitis, diffuse alveolar damage | Reproducibility, increased viral replication in lungs which makes it suitable for immunoprophylaxis and immunotherapy and vaccines studies | As virus is cleared rapidly from 7 to 10 dpi, there was no overt clinical illness | Roberts et al. (2005) |
| 17 | Ferret and domestic cat | SARS-CoV, 106 TCID50, IT | Lethargy and mortality in ferrets; histopathological changes including pulmonary consolidation was reported in both animals | Useful for vaccines, immunotherapy and therapeutic studies | Availability; vulnerability to other respiratory viruses | Martina et al. (2003) |
SARS, Severe acute respiratory syndrome; IN, intranasal inoculation; IT, intratracheal inoculation; IV, intravenous inoculation; IB, intrabronchial inoculation; TCID50, 50% Median Tissue Culture Infectious Dose; PFU, Plaque forming units.