This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Liu, Y.
Right arrow Articles by Tripp, R. A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, Y.
Right arrow Articles by Tripp, R. A.

 Previous Article  |  Next Article 

Journal of Virology, July 2009, p. 6837-6848, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.00379-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Human Metapneumovirus Establishes Persistent Infection in the Lungs of Mice and Is Reactivated by Glucocorticoid Treatment {triangledown}

Yuru Liu,1,{dagger} Debra L. Haas,2,{dagger} Spencer Poore,2 Sanjin Isakovic,2 Michelle Gahan,3 Suresh Mahalingam,3 Zhen F. Fu,1 and Ralph A. Tripp2*

Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602,1 Department of Infectious Diseases, Center for Disease Intervention, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602,2 Centre for Biomedical, Molecular and Chemical Sciences, University of Canberra, Canberra, ACT 2601, Australia3

Received 20 February 2009/ Accepted 30 March 2009

Human metapneumovirus (HMPV) has been identified as a worldwide agent of serious upper and lower respiratory tract infections in infants and young children. HMPV is second only to respiratory syncytial virus (RSV) as a leading cause of bronchiolitis, and, like RSV, consists of two major genotypes that cocirculate and vary among communities year to year. Children who have experienced acute HMPV infection may develop sequelae of wheezing and asthma; however, the features contributing to this pathology remain unknown. A possible mechanism for postbronchiolitis disease is that HMPV might persist in the lung providing a stimulus that could contribute to wheezing and asthma. Using immunohistochemistry to identify HMPV-infected cells in the lungs of mice, we show that HMPV mediates biphasic replication in respiratory epithelial cells then infection migrates to neuronal processes that innervate the lungs where the virus persists with no detectable infection in epithelial cells. After glucocorticoid treatment, the virus is reactivated from neural fibers and reinfects epithelial cells. The findings show that HMPV persists in neural fibers and suggest a mechanism for disease chronicity that has important implications for HMPV disease intervention strategies.

* Corresponding author. Mailing address: Animal Health Research Center, University of Georgia, 111 Carlton Street, Athens, GA 30602. Phone: (706) 542-4312. Fax: (706) 583-0176. E-mail: ratripp{at}uga.edu

{triangledown} Published ahead of print on 8 April 2009.

{dagger} Y.L. and D.H. contributed equally to this study.

Journal of Virology, July 2009, p. 6837-6848, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.00379-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»