Abstract
Infection with human respiratory syncytial virus (hRSV) causes a wide spectrum of respiratory disease in infants, young children, and elderly persons. No vaccine is available today and hRSV treatment options are limited. As a consequence, the treatment of hRSV infection remains largely supportive and new therapeutic options are needed to treat severe lower respiratory tract hRSV disease. Several animal models have been developed to study hRSV disease and evaluate novel therapies or preventive measures such as vaccines. However, each of these models reproduces different aspects of hRSV disease, and therefore, an appropriate model should be selected on the basis of the scientific question under investigation. In this chapter, we describe how cotton rats and Balb/c mice are used in our laboratory to test the in vivo efficacy of small-molecule inhibitors against hRSV.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Chanock R, Roizman B, Myers R (1957) Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). I. Isolation, properties and characterization. Am J Hyg 66:281–290
Chanock R, Finberg L (1957) Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). II. Epidemiologic aspects of infection in infants and young children. Am J Hyg 66:291–300
Ruuskanen O, Lahti E, Jennings LC et al (2011) Viral pneumonia. Lancet 377:1264–1275
Nair H, Nokes JD, Gessner BD et al (2010) Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-Âanalysis. Lancet 375:1545–1555
Collins PL, Crowe JE Jr (2007) Respiratory syncytial virus and metapneumovirus. In: Knipe DM, Howley PM (eds) Fields virology, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1601–1646
Hall CB, Weinberg GA, Iwane MK et al (2009) The burden of respiratory syncytial virus in young children. New Engl J Med 360:588–598
Couch RB, Englund JA, Whimbey E (1997) Respiratory viral infections in immunocompetent and immunocompromised persons. Am J Med 102:2–9
Falsey AR, Hennessey PA, Formica MA et al (2005) Respiratory syncytial virus infection in the elderly and high-risk adults. New Engl J Med 352:1749–1759
Rudan I, Boschi-Pinto C, Biloglav Z et al (2008) Epidemiology and etiology of childhood pneumonia. Bull World Health Organ 86:408–416
Simoes EAF (1999) Respiratory syncytial virus infection. Lancet 354:847–852
Thompson WW, Shay DK, Weintraub E et al (2003) Mortality associated with influenza and respiratory syncytial virus in the United States. J Am Med Assoc 289:179–186
Falsey AR, Walsh EE (2000) Respiratory syncytial virus infection in adults. Clin Microbiol Rev 13:371–384
Roymans D, Koul A (2011) Treatment of respiratory syncytial virus infection: past, present and future. In: Resch B (ed) Human respiratory syncytial virus infection. InTech Europe, Rijeka, pp 197–234
Roymans D, Koul A (2010) Respiratory syncytial virus: a prioritized or neglected target? Future Med Chem 2:1523–1527
Byrd LG, Prince GA (1997) Animal models of respiratory syncytial virus infection. Clin Infect Dis 25:1363–1368
Bem RA, Domachowske JB, Rosenberg HF (2011) Animal models of human respiratory syncytial virus disease. Am J Physiol Lung Cell Mol Physiol 301:L148–L156
Boukhvalova MS, Prince GA, Blanco JCG (2009) The cotton rat model of respiratory viral infections. Biologicals 37:152–159
Rouan M-C, Gevers T, Roymans D et al (2010) Pharmacokinetics-pharmacodynamics of a respiratory syncytial virus fusion inhibitor in the cotton rat model. Antimicrob Agents Chemother 54:4534–4539
Olszewska W, Ispas G, Schnoeller C et al (2011) Antiviral and lung protective activity of a novel respiratory syncytial virus fusion inhibitor in a mouse model. Eur Respir J 38:401–408
Wyde PR, Chetty SN, Timmerman P et al (2003) Short duration aerosols of JNJ 2408068 (R170591) administered prophylactically or therapeutically protect cotton rats from experimental respiratory syncytial virus infection. Antiviral Res 60:221–231
Bonfanti JF, Roymans D (2009) Prospects for the development of fusion inhibitors to treat human respiratory syncytial virus infection. Curr Opin Drug Discov Devel 12:479–487
Cianci C, Genovesi EV, Lamb L et al (2004) Oral efficacy of a respiratory syncytial virus inhibitor in rodent models of infection. Antimicrob Agents Chemother 48:2448–2454
Bonfanti JF, Meyer C, Doublet F et al (2008) Selection of a respiratory syncytial virus fusion inhibitor clinical candidate. 2. Discovery of a morpholinopropylaminobenzimidazole derivative (TMC353121). J Med Chem 51:875–896
Ventre K, Randolph AG (2007) Ribavirin for respiratory syncytial virus infection of the lower respiratory tract in infants and young children. Cochrane Database Syst Rev CD000181
Gupta CK, Leszczynski J, Gupta RK, Siber GR (1996) Stabilization of respiratory syncytial virus (RSV) against thermal inactivation and freeze-thaw cycles for development and control of RSV vaccines and immune globulin. Vaccine 14:1417–1420
Acknowledgments
The authors wish to thank Koen Andries and Tom Gevers for the design of some of the cotton rat protocols described here.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Van den Berg, J., Kwanten, L., Roymans, D. (2013). Evaluation of Antiviral Efficacy Against Human Respiratory Syncytial Virus Using Cotton Rat and Mouse Models. In: Gong, E. (eds) Antiviral Methods and Protocols. Methods in Molecular Biology, vol 1030. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-484-5_28
Download citation
DOI: https://doi.org/10.1007/978-1-62703-484-5_28
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-483-8
Online ISBN: 978-1-62703-484-5
eBook Packages: Springer Protocols