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. 2021 Aug 18;13(8):1641. doi: 10.3390/v13081641

Table 1.

Human viral infections in the tree shrew model.

Virus Species Serotype/Subtype/Genotypes/Strain Inoculum Dose Inoculation Route Age of Animal Viral Load or Titer (Plasma/Serum/Nasal Wash/Tissue) Cytokine and Antibody Response Clinical Signs/Strengths Limitations References
HBV HBV genotype A2, C 1 × 106–1 × 107
GEs/animal		 SC, IP Newborn or adults (1 Y) 10–>103 copies/mL serum IFN-β response impaired in chronic infection, and variable in acute infection; TNF-α expression changes Immunocompetent animal model; viremia develops;
development of both acute and chronic infection; occurrence of histopathological changes in the liver; detection of intrahepatic HBV DNA 		Individual variations of viral replication; intermittent viremia; low viral titer [17,18,19,20]
HCV HCV (genotypes 1a, 1b, 4a, 2a, 2c, 3b, 6) 0.03× 106–12.32×106;
6 × 105
–1 × 107
GEs/animal		 IP, IV Adults (6 M; 1 Y) 4–~104 or 105 copies/mL serum Intrahepatic IFN- β and IL-6 expression changes; anti-NS3 and anti-core Abs produced Viremia develops;
chronic hepatitis; progression of fibrosis; detection of intrahepatic HCV RNA 		Individual variations of viral replication; intermittent viremia; low viral titer [21,22,23]
Influenza A virus H1N1 105 TCID50 IN 3-M-old 102.94–104.24 TCID50/mL Seroconversion Infects tree shrews without prior adaptation; replicates in respiratory tracts; develops acute bronchopneumonia and interstitial pneumonia No loss of appetite, congested eyes and otologic manifestations [24]
Avian influenza A H9N2 106 TCID50 IN Adults 101.5–>105 TCID50/mL Cytokines induced in respiratory tissues; Ab induction Virus replication in respiratory tissues as observed on histology Asymptomatic infection; no virus shedding [25]
Avian influenza A H5N1 1.0 × 106 PFU Multisite inoculation Adult (6M to 4Y-old) 2.8 × 103–5.2 × 107 vRNA copies/mg of lung tissue IFN-γ, IL-6, TNF-α induced; Ab (IgG) induced at 7 dpi Replicates in lung tissues; develops
severe diffuse pneumonia with fever and weight loss		 No sneezing; effect of multisite inoculation on infectivity and pathogenesis yet to be confirmed [26]
Avian influenza A H7N9 (A/Anhui/1/2013) 1.0 × 106 PFU Multisite inoculation Adult (6M to 4Y-old) 6.5 × 101–3.4 × 104 vRNA copies/mg of lung tissue IFN-γ induced; Ab (IgG) induced at 7 dpi Focal pneumonia No sneezing [26]
Avian influenza A H5N1,
H7N9,
H1N1, 		1.0 × 106 EID50 IN 1 to 4 M-old - Neutralizing Ab induced Vaccine efficacy testing [27]
Influenza B virus Strains of Yamagata or Victoria lineage 1.0 × 106 TCID50 IN Adult - Induction of IL-6, IL-10, IP-10, TNF-α and TGF-β mRNA; seroconversion Weight loss, milder nasal secretions No significant respiratory symptoms [28]
SARS-CoV-2 - 106 PFU IN Young (6 M to 12 M), adults (2Y to 4 Y) and old (5 Y to 7 Y) 105.92 vRNA copies/mL (nasal wash) - Increased body temperature; mild pulmonary abnormalities found in histopathology No clinical signs develop [29]
SARS-CoV-2 SARS-CoV-2 strain 107 1 × 107 TCID50 Oral, intranasal, ocular Old (5–6 Y); Adult (1 Y) 1.36 × 103 to
9.32 × 105
copies/g lung tissue		 - vRNA detected in lung tissues and hemorrhage in lung tissues No viremia;
no data on induction of fever		 [30]
Human adenovirus- B (HAdV-B) HAdV-3, HAdV-7, HAdV-14, HAdV-55 5 × 105 TCID50 IN 6–8 M old - Increased expression of IL-8, IL-10, IL-17A, and IFN-γ; Ab produced HAdV efficiently replicates and produced high viral load with severe interstitial pneumonia Presence of pre-existing nAbs against HAdV-3 and HAdV-14 [31]
Dengue virus (DENV) DENV-2DENV-3 1.5 × 103 PFU SC, IV Adult <2 × 104copies/mL serum nAb produced Increased body temperature Very low viremia, lack of severe dengue manifestations [16]
Zika virus (ZIKV) ZIKV strain GZ01 106 PFU SC 5M 104.40–106.02 RNA copies/mL (1 dpi) Strong cytokine response induced; nAb produced Skin rash; suitable for antivirals and vaccine testing No fever or other
neurological and behavioral abnormalities; transient viremia 		[32]
Herpes simplex virus type 1 (HSV-1) HSV-1 strain 17+ 1 × 106 PFU Ocular 6M - - Spontaneous reactivation occurs All HSV-1 genes are not expressed [33]
HSV-1 HSV-1 McKrae virus 1 × 106 PFU Ocular 6M - - Herpes simplex virus keratitis develops; HSV-1 transcripts, ICP0, ICP4, and LAT detected - [34,35]
HSV-1, HSV-2 - 25 –105 PFU SC, IV, IP Juvenile (1–1.5 M) and adult (5M) - - Higher pathogenicity in juveniles and caused death; herpetic hepatitis; encephalitis and fibrosis in the spleen - [36]

TCID50, tissue culture dose 50; PFU, plaque-forming units; EID50, embryo infectious dose 50; GE, genome equivalents; M, month; Y, year; IN, intranasally; vRNA, viral RNA; dpi, days post-infection; nAb, neutralizing antibody.