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. 2007 Oct;171(4):1215-23.
doi: 10.2353/ajpath.2007.070248. Epub 2007 Aug 23.

Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals

Debby van Riel  1 , Vincent J Munster, Emmie de Wit, Guus F Rimmelzwaan, Ron A M Fouchier, Albert D M E Osterhaus, Thijs Kuiken
Affiliations

Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals

Debby van Riel et al. Am J Pathol. 2007 Oct.

Abstract

Viral attachment to the host cell is critical for tissue and species specificity of virus infections. Recently, pattern of viral attachment (PVA) in human respiratory tract was determined for highly pathogenic avian influenza virus of subtype H5N1. However, PVA of human influenza viruses and other avian influenza viruses in either humans or experimental animals is unknown. Therefore, we compared PVA of two human influenza viruses (H1N1 and H3N2) and two low pathogenic avian influenza viruses (H5N9 and H6N1) with that of H5N1 virus in respiratory tract tissues of humans, mice, ferrets, cynomolgus macaques, cats, and pigs by virus histochemistry. We found that human influenza viruses attached more strongly to human trachea and bronchi than H5N1 virus and attached to different cell types than H5N1 virus. These differences correspond to primary diagnoses of tracheobronchitis for human influenza viruses and diffuse alveolar damage for H5N1 virus. The PVA of low pathogenic avian influenza viruses in human respiratory tract resembled that of H5N1 virus, demonstrating that other properties determine its pathogenicity for humans. The PVA in human respiratory tract most closely mirrored that in ferrets and pigs for human influenza viruses and that in ferrets, pigs, and cats for avian influenza viruses.

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Figures

Figure 1
Figure 1
Attachment of human (H3N2 and H1N1) and avian (highly pathogenic H5N1 and low pathogenic H5N9 and H6N1) influenza viruses in human trachea, lower respiratory tract (bronchus, bronchiole, and alveoli), and alveolar macrophages.
Figure 2
Figure 2
Attachment of H3N2 virus and H5N1 virus to the submucosal glands in human, mouse, and ferret trachea.
Figure 3
Figure 3
Confirmation of H5N1 virus attachment to type II pneumocytes in human alveoli by staining for human surfactant apoprotein A (PSP-A). H5N1 virus attachment is visible as red staining on the apical cell surface, whereas PSP-A expression, characteristic for type II pneumocytes, is visible as diffuse dark blue staining in the cytoplasm.
Figure 4
Figure 4
Attachment of H3N2 virus to the trachea and alveoli of human, mouse, ferret, macaque, and cat.
Figure 5
Figure 5
Attachment of H3N2 virus and H5N1 virus to pig trachea and alveoli.
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