The cotton rat (Sigmodon hispidus) is a commonly used model of influenza virus infection in humans because:

  • Cotton rats can be infected by non-adapted human influenza viruses. Both influenza A and B strains replicate in the upper and the lower respiratory tract of cotton rats. Cotton rats can be infected with and replicate avian influenza H3N2 and H9N2 viruses.
  • Virus infection results in histopathological lesions in the lungs that are similar to those seen during natural infection of humans.
  • Virus replication in the lung coincides with the induction of cytokines characteristic of the innate immune response, a potentially important factor in understanding early antiviral mechanisms.
  • Hetero-subtypic (or cross-protective) immunity has been observed in cotton rats as a result of influenza virus infection making the model a valuable tool for the development of broadly active influenza vaccines.

Influenza in Nasal Tissue

Viral titers in nasal tissue homogenates reached more than 105 PFU/g of tissue at Day 1 post infection and then declined to about 103 PFU/g of tissue by Day 4 post infection. See figure above.

Influenza in Lung Tissue

Viral titers in lung homogenates reached more than 106PFU/g of tissue at Day 1 post infection and then declined to about 102 PFU/g of tissue by Day 4 post infection. See figure above.


Cotton rats are infected intranasally under light anesthesia with the influenza virus. The time course of the infection is followed by determining viral titers in nasal or lung tissue homogenates or in bronchoalveolar fluid (BALF).  

The efficacy of test agents in animals challenged with the virus is determined at peak viral titers.

Viral titers are determined via plaque assay or qPCR. H&E stained sections of lung tissue can be prepared for evaluation of tissue histology. 


  • Drug Administration Route: Intranasal, intravenous, intramuscular, continuous infusion

  • Reference Substance & Control: Anti-influenza agents or other reference vehicle

  • Length/Endpoint: Five to seven days post infection

  • Assays & Measurements:  Viral load in nasal tissue, viral load in BALF, viral load in lung homogenate, immunohistochemistry, tissue pathology, cytokine levels


  • Vaccine & antiviral drug development
  • Test adenoviral vector-based gene therapies
  • Study infectious disease pathogenesis

Proven Expertise

We have experience with a variety of mammalian species used for vaccine and drug development. Our studies range from single digit to hundreds of animals.

Our scientists, with over 15 years of GLP experience, provide all aspects of the GLP process from design to regulatory support of your IND, IDE or PMA FDA submission.