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      Severity of Pneumonia Due to New H1N1 Influenza Virus in Ferrets Is Intermediate between That Due to Seasonal H1N1 Virus and Highly Pathogenic Avian Influenza H5N1 Virus

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          Abstract

          Background. The newly emerged influenza A(H1N1) virus (new H1N1 virus) is causing the first influenza pandemic of this century. Three influenza pandemics of the previous century caused variable mortality, which largely depended on the development of severe pneumonia. However, the ability of the new H1N1 virus to cause pneumonia is poorly understood.

          Methods. The new H1N1 virus was inoculated intratracheally into ferrets. Its ability to cause pneumonia was compared with that of seasonal influenza H1N1 virus and highly pathogenic avian influenza (HPAI) H5N1 virus by using clinical, virological, and pathological analyses.

          Results. Our results showed that the new H1N1 virus causes pneumonia in ferrets intermediate in severity between that caused by seasonal H1N1 virus and by HPAI H5N1 virus. The new H1N1 virus replicated well throughout the lower respiratory tract and more extensively than did both seasonal H1N1 virus (which replicated mainly in the bronchi) and HPAI H5N1 virus (which replicated mainly in the alveoli). High loads of new H1N1 virus in lung tissue were associated with diffuse alveolar damage and mortality.

          Conclusions. The new H1N1 virus may be intrinsically more pathogenic for humans than is seasonal H1N1 virus.

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          Most cited references9

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

          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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            Geographic dependence, surveillance, and origins of the 2009 influenza A (H1N1) virus.

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              The ferret: an animal model to study influenza virus.

              There has been much critical influenza research conducted in a little-known laboratory animal--the ferret. The authors review some of these findings, discuss the reasons the ferret often becomes a model for influenza infection, and compare the ferret with other animal models.
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                Author and article information

                Journal
                J Infect Dis
                J. Infect. Dis
                jinfdis
                jid
                The Journal of Infectious Diseases
                The University of Chicago Press
                0022-1899
                1537-6613
                1 April 2010
                1 April 2010
                1 April 2010
                : 201
                : 7
                : 993-999
                Affiliations
                [1 ] Department of Virology, Erasmus Medical Centre , Rotterdam, The Netherlands
                [2 ] ViroClinics Biosciences BV , Rotterdam, The Netherlands
                Author notes
                Reprints or correspondence: Dr A. D. M. E. Osterhaus, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands ( a.osterhaus@ 123456erasmusmc.nl ).
                Article
                10.1086/651132
                7110095
                20187747
                2d77b6af-1308-4af9-9016-8a78668865e6
                © 2010 by the Infectious Diseases Society of America

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                : 4 August 2009
                : 19 October 2009
                Categories
                Major Articles and Brief Reports
                Viruses
                Major Articles

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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