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The cotton rat provides a useful small-animal model for the study of influenza virus pathogenesis
Ist Teil von
Journal of general virology, 2005-10, Vol.86 (10), p.2823-2830
Ort / Verlag
Reading: Soc General Microbiol
Erscheinungsjahr
2005
Quelle
MEDLINE
Beschreibungen/Notizen
1 Department of Pediatrics, F. Edward Hébert School of Medicine, The Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA
2 Virion Systems, Inc., Rockville, MD, USA
Correspondence Martin G. Ottolini mottolini{at}usuhs.mil
Influenza A virus continues to cause annual epidemics. The emergence of avian viruses in the human population poses a pandemic threat, and has highlighted the need for more effective influenza vaccines and antivirals. Development of such therapeutics would be enhanced by the use of a small-animal model that is permissive for replication of human influenza virus, and for which reagents are available to dissect the host response. A model is presented of nasal and pulmonary infection in adult inbred cotton rats ( Sigmodon hispidus ) that does not require viral adaptation. It was previously demonstrated that animals infected intranasally with 10 7 TCID 50 of a recent H3N2 influenza, A/Wuhan/359/95, have increased breathing rates. In this report it is shown that this is accompanied by weight loss and decreased temperature. Virus replication peaked within 24 h in the lung, with peak titres proportional to the infecting dose, clearing by day 3. Replication was more permissive in nasal tissues, and persisted for 6 days. Pulmonary pathology included early bronchiolar epithelial cell damage, followed by extensive alveolar and interstitial pneumonia, which persisted for nearly 3 weeks. Interleukin 1 alpha (IL1 ), alpha interferon (IFN- ), IL6, tumour necrosis factor alpha (TNF- ), GRO and MIP-1 mRNA were elevated soon after infection, and expression coincided with virus replication. A biphasic response was observed for RANTES, IFN- , IL4, IL10 and IL12-p40, with increased mRNA levels early during virus replication followed by a later increase that coincided with pulmonary inflammation. These results indicate that cotton rats will be useful for further studies of influenza pathogenesis and immunity.