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Postgraduate Thesis: Role of indirubin-3'-oxime as antiviral and immunomodulatory agent in influenza H5N1 virus infected human alveolar epithelial cells
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TitleRole of indirubin-3'-oxime as antiviral and immunomodulatory agent in influenza H5N1 virus infected human alveolar epithelial cells
 
AuthorsKang, Sa-rang.
 
Issue Date2012
 
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
 
AbstractContinually reported human cases of highly pathogenic avian influenza (HPAI) H5N1 virus infection create heightened threat to public health, due to the disease severity and high lethality. Acute respiratory syndrome (ARDS) has been found to be the most severe form of acute lung injury caused by H5N1 virus infection. Studies have highlighted that the unusually high virulence of H5N1 virus infection is associated with the cytokine dysregulation and enhanced viral replication in the host. In reference to the past experience during Spanish 1918 influenza pandemic and SARS, it is crucial that a novel therapeutic target is explored and employed in time for the effective control of emerging diseases. The pandemic potential of H5N1 influenza virus urges well preparedness not only in terms of containment measures, but also in the treatment aspect of the severe human H5N1 disease. To date, therapeutic approaches are limited to the use of vaccine, antiviral drugs and corticosteroids. It has been suggested that commercially available antiviral drugs are prone to induce resistance mutations; and are effective in the protection against influenza virus infection only if administered during the early course of disease development. Moreover, vaccine development does not grant a promising therapeutic strategy at the time of a pandemic as it takes time for the development and distribution of safe and reliable vaccine. In attempts to search for a novel adjunctive therapy in addition to currently available agents, indirubin-3’-oxime (IDO) and indirubin derivative, E804 have been tested to show the effect in cytokine suppression and antiviral activity against H5N1 influenza virus infection in vitro. These compounds have been extracted and purified from a natural herb called Isatis tinctoria which is frequently used for herbal remedy in treating respiratory symptoms in traditional Chinese medicine. In this study, it was demonstrated that IDO and E804 treatment in H5N1 influenza virus infected human alveolar epithelial cells effectively inhibit the proinflammatory cytokine induction and viral replication. This physiologically relevant in vitro alveolar epithelial cell model and the efficacy of IDO and E804 provide new insights to the development of new treatment option for severe human H5N1 disease.
 
DegreeMaster of Medical Sciences
 
SubjectAvian influenza A virus.
Epithelial cells.
Antiviral agents.
Indirubin.
 
Dept/ProgramMicrobiology
 
DC FieldValue
dc.contributor.authorKang, Sa-rang.
 
dc.date.hkucongregation2012
 
dc.date.issued2012
 
dc.description.abstractContinually reported human cases of highly pathogenic avian influenza (HPAI) H5N1 virus infection create heightened threat to public health, due to the disease severity and high lethality. Acute respiratory syndrome (ARDS) has been found to be the most severe form of acute lung injury caused by H5N1 virus infection. Studies have highlighted that the unusually high virulence of H5N1 virus infection is associated with the cytokine dysregulation and enhanced viral replication in the host. In reference to the past experience during Spanish 1918 influenza pandemic and SARS, it is crucial that a novel therapeutic target is explored and employed in time for the effective control of emerging diseases. The pandemic potential of H5N1 influenza virus urges well preparedness not only in terms of containment measures, but also in the treatment aspect of the severe human H5N1 disease. To date, therapeutic approaches are limited to the use of vaccine, antiviral drugs and corticosteroids. It has been suggested that commercially available antiviral drugs are prone to induce resistance mutations; and are effective in the protection against influenza virus infection only if administered during the early course of disease development. Moreover, vaccine development does not grant a promising therapeutic strategy at the time of a pandemic as it takes time for the development and distribution of safe and reliable vaccine. In attempts to search for a novel adjunctive therapy in addition to currently available agents, indirubin-3’-oxime (IDO) and indirubin derivative, E804 have been tested to show the effect in cytokine suppression and antiviral activity against H5N1 influenza virus infection in vitro. These compounds have been extracted and purified from a natural herb called Isatis tinctoria which is frequently used for herbal remedy in treating respiratory symptoms in traditional Chinese medicine. In this study, it was demonstrated that IDO and E804 treatment in H5N1 influenza virus infected human alveolar epithelial cells effectively inhibit the proinflammatory cytokine induction and viral replication. This physiologically relevant in vitro alveolar epithelial cell model and the efficacy of IDO and E804 provide new insights to the development of new treatment option for severe human H5N1 disease.
 
dc.description.naturepublished_or_final_version
 
dc.description.thesisdisciplineMicrobiology
 
dc.description.thesislevelmaster's
 
dc.description.thesisnameMaster of Medical Sciences
 
dc.identifier.hkulb4833394
 
dc.languageeng
 
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)
 
dc.relation.ispartofHKU Theses Online (HKUTO)
 
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.source.urihttp://hub.hku.hk/bib/B48333943
 
dc.subject.lcshAvian influenza A virus.
 
dc.subject.lcshEpithelial cells.
 
dc.subject.lcshAntiviral agents.
 
dc.subject.lcshIndirubin.
 
dc.titleRole of indirubin-3'-oxime as antiviral and immunomodulatory agent in influenza H5N1 virus infected human alveolar epithelial cells
 
dc.typePG_Thesis
 
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<item><contributor.author>Kang, Sa-rang.</contributor.author>
<date.issued>2012</date.issued>
<description.abstract>&#65279;Continually reported human cases of highly pathogenic avian influenza (HPAI) H5N1 virus infection create heightened threat to public health, due to the disease severity and high lethality. Acute respiratory syndrome (ARDS) has been found to be the most severe form of acute lung injury caused by H5N1 virus infection. Studies have highlighted that the unusually high virulence of H5N1 virus infection is associated with the cytokine dysregulation and enhanced viral replication in the host. 

In reference to the past experience during Spanish 1918 influenza pandemic and SARS, it is crucial that a novel therapeutic target is explored and employed in time for the effective control of emerging diseases. The pandemic potential of H5N1 influenza virus urges well preparedness not only in terms of containment measures, but also in the treatment aspect of the severe human H5N1 disease. To date, therapeutic approaches are limited to the use of vaccine, antiviral drugs and corticosteroids. It has been suggested that commercially available antiviral drugs are prone to induce resistance mutations; and are effective in the protection against influenza virus infection only if administered during the early course of disease development. Moreover, vaccine development does not grant a promising therapeutic strategy at the time of a pandemic as it takes time for the development and distribution of safe and reliable vaccine. 

In attempts to search for a novel adjunctive therapy in addition to currently available agents, indirubin-3&#8217;-oxime (IDO) and indirubin derivative, E804 have been tested to show the effect in cytokine suppression and antiviral activity against H5N1 influenza virus infection in vitro. These compounds have been extracted and purified from a natural herb called Isatis tinctoria which is frequently used for herbal remedy in treating respiratory symptoms in traditional Chinese medicine. 

In this study, it was demonstrated that IDO and E804 treatment in H5N1 influenza virus infected human alveolar epithelial cells effectively inhibit the proinflammatory cytokine induction and viral replication. This physiologically relevant in vitro alveolar epithelial cell model and the efficacy of IDO and E804 provide new insights to the development of new treatment option for severe human H5N1 disease.</description.abstract>
<language>eng</language>
<publisher>The University of Hong Kong (Pokfulam, Hong Kong)</publisher>
<relation.ispartof>HKU Theses Online (HKUTO)</relation.ispartof>
<rights>The author retains all proprietary rights, (such as patent rights) and the right to use in future works.</rights>
<rights>Creative Commons: Attribution 3.0 Hong Kong License</rights>
<source.uri>http://hub.hku.hk/bib/B48333943</source.uri>
<subject.lcsh>Avian influenza A virus.</subject.lcsh>
<subject.lcsh>Epithelial cells.</subject.lcsh>
<subject.lcsh>Antiviral agents.</subject.lcsh>
<subject.lcsh>Indirubin.</subject.lcsh>
<title>Role of indirubin-3&apos;-oxime as antiviral and immunomodulatory agent in influenza H5N1 virus infected human alveolar epithelial cells</title>
<type>PG_Thesis</type>
<identifier.hkul>b4833394</identifier.hkul>
<description.thesisname>Master of Medical Sciences</description.thesisname>
<description.thesislevel>master&apos;s</description.thesislevel>
<description.thesisdiscipline>Microbiology</description.thesisdiscipline>
<description.nature>published_or_final_version</description.nature>
<date.hkucongregation>2012</date.hkucongregation>
<bitstream.url>http://hub.hku.hk/bitstream/10722/173845/1/FullText.pdf</bitstream.url>
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