The Antiviral Potential of Host Histone Deacetylase 11 during Influenza Virus Infection
|dc.identifier.citation||Nutsford, A. (2017). The Antiviral Potential of Host Histone Deacetylase 11 during Influenza Virus Infection (Thesis, Master of Science). University of Otago. Retrieved from http://hdl.handle.net/10523/7494||en|
|dc.description.abstract||Influenza A virus (IAV) continues to have a major impact on global public health by causing regular seasonal epidemics, unpredictable pandemics and zoonotic outbreaks. These events also have significant implications for global economy and productivity. The ability of IAV to undergo constant evolution has impeded the development of a universal influenza vaccine. Furthermore, of the two approved classes of anti-influenza drugs, one (adamantanes) has become obsolete; whereas the other (neuraminidase inhibitors) is inclined to become ineffective overtime, due to the acquisition of drug-resistance by IAV. This means alternative anti-influenza virus strategies are urgently needed. Strengthening the host antiviral response against IAV could be one such strategy. However, to accomplish this, the complete repertoire of anti-IAV host factors needs to be identified and their antiviral mechanisms elucidated. This MSc research project was planned to identify the potential antiviral role of host enzyme, histone deacetylase 11 (HDAC11), in IAV infection. Histone deacetylases are a multi-class family of host enzymes implicated in cellular functions, disorders and diseases - including viral infection. Previous work done in our laboratory has discovered the anti-IAV functions for class I members HDAC 1 and 2, and class II member HDAC6. HDAC11, the sole member of class IV, exhibits a shared homology to both class I and II members. Based on this, we hypothesised that HDAC11 also plays an antiviral role during IAV infection. Viruses are known to modulate the expression of host factors involved in infection. Therefore, first, we analysed the HDAC11 expression in human lung epithelial cells in response to infection with a lab-adapted and a clinical IAV strain. We found that IAV downregulates HDAC11 expression both at mRNA and polypeptide level in a dose-dependent and time-dependent manner. These data indicated that HDAC11 is potentially an anti-IAV factor. To further assess this, IAV infection was analysed in HDAC11-depleted or HDAC11-overexpressing cells. Here we observed an almost 10-fold increase in IAV release in HDAC11-depleted cells. Conversely, the ectopic expression of HDAC11 caused a 45% decrease in IAV release. Taken together, these data indicate a novel finding - that host HDAC11 is an anti-IAV host factor. Future research will determine the antiviral mechanism of HDAC11 during IAV infection. Furthermore, the identification of a similar role for other HDACs and characterisation of their potentially co-operative antiviral function in IAV infection may provide new targets for enhancing the host antiviral response to combat IAV infection.|
|dc.publisher||University of Otago|
|dc.rights||All items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.|
|dc.subject||Histone Deacetylase 11|
|dc.title||The Antiviral Potential of Host Histone Deacetylase 11 during Influenza Virus Infection|
|thesis.degree.discipline||Microbiology and Immunology|
|thesis.degree.name||Master of Science|
|thesis.degree.grantor||University of Otago|
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