1887

Abstract

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 () that does not require viral ‘adaptation’. It was previously demonstrated that animals infected intranasally with 10 TCID 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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81145-0
2005-10-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/10/2823.html?itemId=/content/journal/jgv/10.1099/vir.0.81145-0&mimeType=html&fmt=ahah

References

  1. Berendt R. F., Scott G. H. 1977; Evaluation of commercially prepared vaccines for experimentally induced type A/New Jersey/8/76 influenza virus infections in mice and squirrel monkeys. J Infect Dis 136:S712–S717 [CrossRef]
    [Google Scholar]
  2. Blanco J. C. G., Richardson J. Y., Darnell M. E. R., Rowzee A., Pletneva L., Porter D. D., Prince G. A. 2002; Cytokine and chemokine gene expression after primary and secondary respiratory syncytial virus infection in cotton rats. J Infect Dis 185:1780–1785 [CrossRef]
    [Google Scholar]
  3. Blanco J. C. G., Pletneva L., Boukhvalova M., Richardson J. Y., Harris K. A., Prince G. A. 2004; The cotton rat: an underutilized animal model for human infectious diseases can now be exploited using specific reagents to cytokines, chemokines, and interferons. J Interferon Cytokine Res 24:21–28 [CrossRef]
    [Google Scholar]
  4. Blatteis C. M., Li S., Li Z., Feleder C., Perlik V. 2005; Cytokines, PGE2 and endotoxic fever: a re-assessment. Prostaglandins Other Lipid Mediat 76:1–18 [CrossRef]
    [Google Scholar]
  5. Conn C. A., McClellan J. L., Maassab H. F., Smitka C. W., Majde J. A., Kluger M. J. 1995; Cytokines and the acute phase response to influenza virus in mice. Am J Physiol 268:R78–R84
    [Google Scholar]
  6. Eichelberger M. C., Prince G. A., Ottolini M. G. 2004; Influenza-induced tachypnea is prevented in immune cotton rats, but cannot be treated with an anti-inflammatory steroid or a neuraminidase inhibitor. Virology 322:300–307 [CrossRef]
    [Google Scholar]
  7. Haller O., Arnheiter H., Gresser I., Lindenmann J. 1979; Genetically determined, interferon-dependent resistance to influenza virus in mice. J Exp Med 149:601–612 [CrossRef]
    [Google Scholar]
  8. Hayden F. G., Fritz R. S., Lobo M. C., Alvord W. G., Strober W., Straus S. E. 1998; Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense. J Clin Invest 101:643–649 [CrossRef]
    [Google Scholar]
  9. Hennet T., Ziltener H. J., Frei K., Peterhans E. 1992; A kinetic study of immune mediators in the lungs of mice infected with influenza A virus. J Immunol 149:932–939
    [Google Scholar]
  10. Herlocher M. L., Elias S., Truscon R., Harrison S., Mindell D., Simon C., Monto A. S. 2001; Ferrets as a transmission model for influenza: sequence changes in HA1 of type A (H3N2) virus. J Infect Dis 184:542–546 [CrossRef]
    [Google Scholar]
  11. Herlocher M. L., Truscon R., Fenton R., Klimov A., Elias S., Ohmit S. E., Monto A. S. 2003; Assessment of development of resistance to antivirals in the ferret model of influenza virus infection. J Infect Dis 188:1355–1361 [CrossRef]
    [Google Scholar]
  12. Klein J. O. 2001; Bacterial sepsis and meningitis. In Infectious Diseases of the Fetus and Newborn Infant . , 5th edn. pp  964–967 Edited by Remington J., Klein J. O. Philadelphia, PA: Saunders;
  13. Krug R. M., Shaw M., Broni B., Shapiro G., Haller O. 1985; Inhibition of influenza viral mRNA synthesis in cells expressing the interferon-induced Mx gene product. J Virol 56:201–206
    [Google Scholar]
  14. Lindenmann J., Lane C. A., Hobson D. 1963; The resistance of A2G mice to myxoviruses. J Immunol 90:942–951
    [Google Scholar]
  15. Murphy B. R., Baron S., Chalhub E. G., Uhlendorf C. P., Chanock R. M. 1973; Temperature-sensitive mutants of influenza virus. IV. Induction of interferon in the nasopharynx by wild-type and a temperature-sensitive recombinant virus. J Infect Dis 128:488–493 [CrossRef]
    [Google Scholar]
  16. Murphy B. R., Sly D. L., Hosier N. T., London W. T., Chanock R. M. 1980; Evaluation of three strains of influenza A virus in humans and in owl, cebus, and squirrel monkeys. Infect Immun 28:688–691
    [Google Scholar]
  17. Olshaker J. S. 2003; Influenza. Emerg Med Clin North Am 21:353–361 [CrossRef]
    [Google Scholar]
  18. Ottolini M., Blanco J., Porter D., Peterson L., Curtis S., Prince G. A. 2003; Combination anti-inflammatory and antiviral therapy of influenza in a cotton rat model. Pediatr Pulmonol 36:290–294 [CrossRef]
    [Google Scholar]
  19. Prince G. A., Curtis S. J., Yim K. C., Porter D. D. 2001; Vaccine-enhanced respiratory syncytial virus disease in cotton rats following immunization with Lot 100 or a newly prepared reference vaccine. J Gen Virol 82:2881–2888
    [Google Scholar]
  20. Renegar K. B. 1992; Influenza virus infections and immunity: a review of human and animal models. Lab Anim Sci 42:222–232
    [Google Scholar]
  21. Romanovsky A. A. 2000; Thermoregulatory manifestations of systemic inflammation: lessons from vagotomy. Auton Neurosci 85:39–48 [CrossRef]
    [Google Scholar]
  22. Romanovsky A. A., Ivanov A. I., Shimansky Y. P. 2002; Molecular biology of thermoregulation. Selected contribution: ambient temperature for experiments in rats: a new method for determining the zone of thermal neutrality. J Appl Physiol 92:2667–2679 [CrossRef]
    [Google Scholar]
  23. Sadowski W., Wilczynski J., Semkow R., Tulimowska M., Krus S., Kantoch M. 1987; Cotton rat ( Sigmodon hispidus ) as an experimental model for study of respiratory tract viral infections in man. II. Influenza virus A and B. Med Dosw Mikrobiol 39:43–55
    [Google Scholar]
  24. Scott G. H., Stephen E. L., Berendt R. F. 1978; Activity of amantadine, rimantadine, and ribavirin against swine influenza in mice and squirrel monkeys. Antimicrob Agents Chemother 13:284–288 [CrossRef]
    [Google Scholar]
  25. Seo S. H., Hoffmann E., Webster R. G. 2002; Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nat Med 8:950–954 [CrossRef]
    [Google Scholar]
  26. Smith H., Sweet C. 1988; Lessons for human influenza from pathogenicity studies with ferrets. Rev Infect Dis 10:56–75 [CrossRef]
    [Google Scholar]
  27. Smith W., Andrewes C. H., Laidlaw P. P. 1933; A virus obtained from influenza patients. Lancet 222:66–68 [CrossRef]
    [Google Scholar]
  28. Van Reeth K., Van Gucht S., Pensaert M. 2002; Correlations between lung proinflammatory cytokine levels, virus replication, and disease after swine influenza virus challenge of vaccination-immune pigs. Viral Immunol 15:583–594 [CrossRef]
    [Google Scholar]
  29. World Health Organization 2004; WHO Manual on Animal Influenza Diagnosis and Surveillance ; WHO/CDS/CSR/NCS/2002·5Rev.1 http://www.who.int/entity/csr/resources/publications/influenza/WHO_CDS_CSR_NCS_2002_5/en
  30. Zitzow L. A., Rowe T., Morken T., Shieh W. J., Zaki S., Katz J. M. 2002; Pathogenesis of avian influenza A (H5N1) viruses in ferrets. J Virol 76:4420–4429 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81145-0
Loading
/content/journal/jgv/10.1099/vir.0.81145-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error