Giuseppe
Emeritus
Tropism and Innate Host Responses of the 2009 Pandemic H1N1 Influenza Virus in ex Vivo and in Vitro Cultures of Human Conjunctiva and Respiratory Tract (American Journal of Pathology, abstract, edited)
Published online before print January 28, 2010
Copyright ? 2010 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2010.091087
Accepted for publication December 15, 2009.
Regular Article
Tropism and Innate Host Responses of the 2009 Pandemic H1N1 Influenza Virus in ex Vivo and in Vitro Cultures of Human Conjunctiva and Respiratory Tract
Michael C.W. Chan*@, Renee W.Y. Chan*, Wendy C.L. Yu*, Carol C.C. Ho*, Kit M. Yuen*, Joanne H.M. Fong*, Lynsia L.S. Tang*, Wico W. Lai, Amy C.Y. Lo, W. H. Chui, Alan D.L. Sihoe, Dora L.W. Kwong?, David S.H. Wong, George S.W. Tsao||, Leo L.M. Poon*, Yi Guan*, John M. Nicholls, and Joseph S.M. Peiris**
@From the Departments of Microbiology* and Pathology, the Eye Institute, and the Departments of Cardiothoracic Surgery, Clinical Oncology,? and Anatomy,|| the University of Hong Kong, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China; and HKU-Pasteur Research Centre,** Hong Kong SAR, China
@ To whom correspondence should be addressed. E-mail: mchan@hkucc.hku.hk.
Abstract
The novel pandemic influenza H1N1 (H1N1pdm) virus of swine origin causes mild disease but occasionally leads to acute respiratory distress syndrome and death. It is important to understand the pathogenesis of this new disease in humans. We compared the virus tropism and host-responses elicited by pandemic H1N1pdm and seasonal H1N1 influenza viruses in ex vivo cultures of human conjunctiva, nasopharynx, bronchus, and lung, as well as in vitro cultures of human nasopharyngeal, bronchial, and alveolar epithelial cells. We found comparable replication and host-responses in seasonal and pandemic H1N1 viruses. However, pandemic H1N1pdm virus differs from seasonal H1N1 influenza virus in its ability to replicate in human conjunctiva, suggesting subtle differences in its receptor-binding profile and highlighting the potential role of the conjunctiva as an additional route of infection with H1N1pdm. A greater viral replication competence in bronchial epithelium at 33?C may also contribute to the slight increase in virulence of the pandemic influenza virus. In contrast with highly pathogenic influenza H5N1 virus, pandemic H1N1pdm does not differ from seasonal influenza virus in its intrinsic capacity for cytokine dysregulation. Collectively, these results suggest that pandemic H1N1pdm virus differs in modest but subtle ways from seasonal H1N1 virus in its intrinsic virulence for humans, which is in accord with the epidemiology of the pandemic to date. These findings are therefore relevant for understanding transmission and therapy.
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<cite cite="http://ajp.amjpathol.org/cgi/content/abstract/ajpath.2010.091087v1">Tropism and Innate Host Responses of the 2009 Pandemic H1N1 Influenza Virus in ex Vivo and in Vitro Cultures of Human Conjunctiva and Respiratory Tract -- Chan et al., 10.2353/ajpath.2010.091087 -- American Journal of Pathology</cite>Copyright ? 2010 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2010.091087
Accepted for publication December 15, 2009.
Regular Article
Tropism and Innate Host Responses of the 2009 Pandemic H1N1 Influenza Virus in ex Vivo and in Vitro Cultures of Human Conjunctiva and Respiratory Tract
Michael C.W. Chan*@, Renee W.Y. Chan*, Wendy C.L. Yu*, Carol C.C. Ho*, Kit M. Yuen*, Joanne H.M. Fong*, Lynsia L.S. Tang*, Wico W. Lai, Amy C.Y. Lo, W. H. Chui, Alan D.L. Sihoe, Dora L.W. Kwong?, David S.H. Wong, George S.W. Tsao||, Leo L.M. Poon*, Yi Guan*, John M. Nicholls, and Joseph S.M. Peiris**
@From the Departments of Microbiology* and Pathology, the Eye Institute, and the Departments of Cardiothoracic Surgery, Clinical Oncology,? and Anatomy,|| the University of Hong Kong, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China; and HKU-Pasteur Research Centre,** Hong Kong SAR, China
@ To whom correspondence should be addressed. E-mail: mchan@hkucc.hku.hk.
Abstract
The novel pandemic influenza H1N1 (H1N1pdm) virus of swine origin causes mild disease but occasionally leads to acute respiratory distress syndrome and death. It is important to understand the pathogenesis of this new disease in humans. We compared the virus tropism and host-responses elicited by pandemic H1N1pdm and seasonal H1N1 influenza viruses in ex vivo cultures of human conjunctiva, nasopharynx, bronchus, and lung, as well as in vitro cultures of human nasopharyngeal, bronchial, and alveolar epithelial cells. We found comparable replication and host-responses in seasonal and pandemic H1N1 viruses. However, pandemic H1N1pdm virus differs from seasonal H1N1 influenza virus in its ability to replicate in human conjunctiva, suggesting subtle differences in its receptor-binding profile and highlighting the potential role of the conjunctiva as an additional route of infection with H1N1pdm. A greater viral replication competence in bronchial epithelium at 33?C may also contribute to the slight increase in virulence of the pandemic influenza virus. In contrast with highly pathogenic influenza H5N1 virus, pandemic H1N1pdm does not differ from seasonal influenza virus in its intrinsic capacity for cytokine dysregulation. Collectively, these results suggest that pandemic H1N1pdm virus differs in modest but subtle ways from seasonal H1N1 virus in its intrinsic virulence for humans, which is in accord with the epidemiology of the pandemic to date. These findings are therefore relevant for understanding transmission and therapy.
-