help button home button Am J Pathol R & D Systems
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kuiken, T.
Right arrow Articles by Osterhaus, A. D.M.E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kuiken, T.
Right arrow Articles by Osterhaus, A. D.M.E.
(American Journal of Pathology. 2004;164:1893-1900.)
© 2004 American Society for Investigative Pathology


Short Communication

Experimental Human Metapneumovirus Infection of Cynomolgus Macaques (Macaca fascicularis) Results in Virus Replication in Ciliated Epithelial Cells and Pneumocytes with Associated Lesions throughout the Respiratory Tract

Thijs Kuiken*, Bernadette G. van den Hoogen*, Debby A.J. van Riel{dagger}, Jon D. Laman{dagger}, Geert van Amerongen*, Leo Sprong*, Ron A.M. Fouchier* and Albert D.M.E. Osterhaus*

From the Departments of Virology*and Immunology{dagger}, Erasmus Medical Center, Rotterdam, the Netherlands

A substantial proportion of hitherto unexplained respiratory tract illnesses is associated with human metapneumovirus (hMPV) infection. This virus also was found in patients with severe acute respiratory syndrome (SARS). To determine the dynamics and associated lesions of hMPV infection, six cynomolgus macaques (Macaca fascicularis) were inoculated with hMPV and examined by pathological and virological assays. They were euthanized at 5 (n = 2) or 9 (n = 2) days post-infection (dpi), or monitored until 14 dpi (n = 2). Viral excretion peaked at 4 dpi and decreased to zero by 10 dpi. Viral replication was restricted to the respiratory tract and associated with minimal to mild, multi-focal erosive and inflammatory changes in conducting airways, and increased numbers of macrophages in alveoli. Viral expression was seen mainly at the apical surface of ciliated epithelial cells throughout the respiratory tract, and less frequently in type 1 pneumocytes and alveolar macrophages. Both cell tropism and respiratory lesions were distinct from those of SARS-associated coronavirus infection, excluding hMPV as the primary cause of SARS. This study demonstrates that hMPV is a respiratory pathogen and indicates that viral replication is short-lived, polarized to the apical surface, and occurs primarily in ciliated respiratory epithelial cells.





This article has been cited by other articles:


Home page
J. Virol.Home page
Y. Liu, D. L. Haas, S. Poore, S. Isakovic, M. Gahan, S. Mahalingam, Z. F. Fu, and R. A. Tripp
Human Metapneumovirus Establishes Persistent Infection in the Lungs of Mice and Is Reactivated by Glucocorticoid Treatment
J. Virol., July 1, 2009; 83(13): 6837 - 6848.
[Abstract] [Full Text] [PDF]


Home page
J. Gen. Virol.Home page
M. de Graaf, E. J. A. Schrauwen, S. Herfst, G. van Amerongen, A. D. M. E. Osterhaus, and R. A. M. Fouchier
Fusion protein is the main determinant of metapneumovirus host tropism
J. Gen. Virol., June 1, 2009; 90(6): 1408 - 1416.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
R. M. Schowalter, A. Chang, J. G. Robach, U. J. Buchholz, and R. E. Dutch
Low-pH Triggering of Human Metapneumovirus Fusion: Essential Residues and Importance in Entry
J. Virol., February 1, 2009; 83(3): 1511 - 1522.
[Abstract] [Full Text] [PDF]


Home page
J. Gen. Virol.Home page
S. Herfst, M. de Graaf, E. J. A. Schrauwen, L. Sprong, K. Hussain, B. G. van den Hoogen, A. D. M. E. Osterhaus, and R. A. M. Fouchier
Generation of temperature-sensitive human metapneumovirus strains that provide protective immunity in hamsters
J. Gen. Virol., July 1, 2008; 89(7): 1553 - 1562.
[Abstract] [Full Text] [PDF]


Home page
J. Gen. Virol.Home page
M. de Graaf, S. Herfst, E. J. A. Schrauwen, Y. Choi, B. G. van den Hoogen, A. D. M. E. Osterhaus, and R. A. M. Fouchier
Specificity and functional interaction of the polymerase complex proteins of human and avian metapneumoviruses
J. Gen. Virol., April 1, 2008; 89(4): 975 - 983.
[Abstract] [Full Text] [PDF]


Home page
J. Gen. Virol.Home page
S. Herfst, M. de Graaf, E. J. A. Schrauwen, N. D. Ulbrandt, A. S. Barnes, K. Senthil, A. D. M. E. Osterhaus, R. A. M. Fouchier, and B. G. van den Hoogen
Immunization of Syrian golden hamsters with F subunit vaccine of human metapneumovirus induces protection against challenge with homologous or heterologous strains
J. Gen. Virol., October 1, 2007; 88(10): 2702 - 2709.
[Abstract] [Full Text] [PDF]


Home page
J. Gen. Virol.Home page
B. G. van den Hoogen, S. Herfst, M. de Graaf, L. Sprong, R. van Lavieren, G. van Amerongen, S. Yuksel, R. A. M. Fouchier, A. D. M. E. Osterhaus, and R. L. de Swart
Experimental infection of macaques with human metapneumovirus induces transient protective immunity
J. Gen. Virol., April 1, 2007; 88(4): 1251 - 1259.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
T. Baas, C. R. Baskin, D. L. Diamond, A. Garcia-Sastre, H. Bielefeldt-Ohmann, T. M. Tumpey, M. J. Thomas, V. S. Carter, T. H. Teal, N. Van Hoeven, et al.
Integrated Molecular Signature of Disease: Analysis of Influenza Virus-Infected Macaques through Functional Genomics and Proteomics
J. Virol., November 1, 2006; 80(21): 10813 - 10828.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
R. N. Douville, N. Bastien, Y. Li, P. Pochard, F. E. R. Simons, and K. T. HayGlass
Human Metapneumovirus Elicits Weak IFN-{gamma} Memory Responses Compared with Respiratory Syncytial Virus
J. Immunol., May 15, 2006; 176(10): 5848 - 5855.
[Abstract] [Full Text] [PDF]


Home page
ANN INTERN MEDHome page
J. A. Englund, M. Boeckh, J. Kuypers, W. G. Nichols, R. C. Hackman, R. A. Morrow, D. N. Fredricks, and L. Corey
Brief communication: fatal human metapneumovirus infection in stem-cell transplant recipients.
Ann Intern Med, March 7, 2006; 144(5): 344 - 349.
[Abstract] [Full Text] [PDF]


Home page
ANN INTERN MEDHome page
J.-A. H. van Burik
Human metapneumovirus: important but not currently diagnosable.
Ann Intern Med, March 7, 2006; 144(5): 374 - 375.
[Full Text] [PDF]


Home page
J. Virol.Home page
J. V. Williams, S. J. Tollefson, J. E. Johnson, and J. E. Crowe Jr.
The Cotton Rat (Sigmodon hispidus) Is a Permissive Small Animal Model of Human Metapneumovirus Infection, Pathogenesis, and Protective Immunity
J. Virol., September 1, 2005; 79(17): 10944 - 10951.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
M.-E. Hamelin, K. Yim, K. H. Kuhn, R. P. Cragin, M. Boukhvalova, J. C. G. Blanco, G. A. Prince, and G. Boivin
Pathogenesis of Human Metapneumovirus Lung Infection in BALB/c Mice and Cotton Rats
J. Virol., July 15, 2005; 79(14): 8894 - 8903.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Microbiol.Home page
T. Ebihara, R. Endo, X. Ma, N. Ishiguro, and H. Kikuta
Detection of Human Metapneumovirus Antigens in Nasopharyngeal Secretions by an Immunofluorescent-Antibody Test
J. Clin. Microbiol., March 1, 2005; 43(3): 1138 - 1141.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2004 by the American Society for Investigative Pathology.