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Journal of Virology, September 2005, p. 10944-10951, Vol. 79, No. 17
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.17.10944-10951.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Cotton Rat (Sigmodon hispidus) Is a Permissive Small Animal Model of Human Metapneumovirus Infection, Pathogenesis, and Protective Immunity

John V. Williams,1* Sharon J. Tollefson,1 Joyce E. Johnson,2 and James E. Crowe Jr.1,3

Departments of Pediatrics,1 Pathology,2 Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee3

Received 10 February 2005/ Accepted 25 May 2005

Human metapneumovirus (hMPV) is a newly described paramyxovirus that is an important cause of acute respiratory tract disease. We undertook to develop a small animal model of hMPV infection, pathogenesis, and protection. Hamsters, guinea pigs, cotton rats, and nine inbred strains of mice were inoculated intranasally with hMPV. The animals were sacrificed, and nasal and lung tissue virus yields were determined by plaque titration. None of the animals exhibited respiratory symptoms. The quantity of virus present in the nasal tissue ranged from 4.6 x 102 PFU/gram tissue (C3H mice) to greater than 105 PFU/gram (hamster). The amount of virus in the lungs was considerably less than in nasal tissue in each species tested, ranging from undetectable (<5 PFU/g; guinea pigs) to 1.8 x 105 PFU/gram (cotton rat). The peak virus titer in cotton rat lungs occurred on day 4 postinfection. hMPV-infected cotton rat lungs examined on day 4 postinfection exhibited histopathological changes consisting of peribronchial inflammatory infiltrates. Immunohistochemical staining detected virus only at the luminal surfaces of respiratory epithelial cells throughout the respiratory tract. hMPV-infected cotton rats mounted virus-neutralizing antibody responses and were partially protected against virus shedding and lung pathology on subsequent rechallenge with hMPV. Viral antigen was undetectable in the lungs on challenge of previously infected animals. This study demonstrates that the cotton rat is a permissive small animal model of hMPV infection that exhibits lung histopathology associated with infection and that primary infection protected animals against subsequent infection. This model will allow further in vivo studies of hMPV pathogenesis and evaluation of vaccine candidates.

* Corresponding author. Mailing address: Pediatric Infectious Diseases, Vanderbilt University Medical Center, D-7235 Medical Center North, 1161 21st Avenue South, Nashville, TN 37232-2581. Phone: (615) 936-2186. Fax: (615) 343-9723. E-mail: john.williams{at}vanderbilt.edu.

Journal of Virology, September 2005, p. 10944-10951, Vol. 79, No. 17
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.17.10944-10951.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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