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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

Identifieur interne : 005B38 ( Main/Exploration ); précédent : 005B37; suivant : 005B39

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

Auteurs : Thijs Kuiken [Pays-Bas] ; Bernadette G. Van Den Hoogen [Pays-Bas] ; Debby A. J. Van Riel [Pays-Bas] ; Jon D. Laman [Pays-Bas] ; Geert Van Amerongen [Pays-Bas] ; Leo Sprong [Pays-Bas] ; Ron A. M. Fouchier [Pays-Bas] ; Albert D. M. E. Osterhaus [Pays-Bas]

Source :

RBID : Pascal:04-0317025

Descripteurs français

English descriptors

Abstract

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.

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<term>Animals</term>
<term>Association</term>
<term>Bronchi (pathology)</term>
<term>Bronchi (virology)</term>
<term>Cilia (virology)</term>
<term>Ciliated cell</term>
<term>Disease Models, Animal</term>
<term>Epithelial Cells (ultrastructure)</term>
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<term>Disease Models, Animal</term>
<term>Humans</term>
<term>Macaca fascicularis</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Infection</term>
<term>Etude expérimentale</term>
<term>Homme</term>
<term>Singe</term>
<term>Macaca fascicularis</term>
<term>Virus</term>
<term>Réplication</term>
<term>Cellule ciliée</term>
<term>Cellule épithéliale</term>
<term>Pneumocyte</term>
<term>Association</term>
<term>Lésion</term>
<term>Voie respiratoire</term>
<term>Médecine</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr">
<term>Homme</term>
<term>Singe</term>
<term>Association</term>
<term>Médecine</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">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.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Pays-Bas</li>
</country>
<region>
<li>Hollande-Méridionale</li>
</region>
<settlement>
<li>Rotterdam</li>
</settlement>
</list>
<tree>
<country name="Pays-Bas">
<region name="Hollande-Méridionale">
<name sortKey="Kuiken, Thijs" sort="Kuiken, Thijs" uniqKey="Kuiken T" first="Thijs" last="Kuiken">Thijs Kuiken</name>
</region>
<name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A. M." last="Fouchier">Ron A. M. Fouchier</name>
<name sortKey="Laman, Jon D" sort="Laman, Jon D" uniqKey="Laman J" first="Jon D." last="Laman">Jon D. Laman</name>
<name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D. M. E." last="Osterhaus">Albert D. M. E. Osterhaus</name>
<name sortKey="Sprong, Leo" sort="Sprong, Leo" uniqKey="Sprong L" first="Leo" last="Sprong">Leo Sprong</name>
<name sortKey="Van Amerongen, Geert" sort="Van Amerongen, Geert" uniqKey="Van Amerongen G" first="Geert" last="Van Amerongen">Geert Van Amerongen</name>
<name sortKey="Van Den Hoogen, Bernadette G" sort="Van Den Hoogen, Bernadette G" uniqKey="Van Den Hoogen B" first="Bernadette G." last="Van Den Hoogen">Bernadette G. Van Den Hoogen</name>
<name sortKey="Van Riel, Debby A J" sort="Van Riel, Debby A J" uniqKey="Van Riel D" first="Debby A. J." last="Van Riel">Debby A. J. Van Riel</name>
</country>
</tree>
</affiliations>
</record>

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