The study of highly pathogenic emerging zoonotic virus envelope proteins through pseudotyped virus generation
Emerging zoonotic viruses pose an increasing threat, causing outbreaks with high rates of morbidity and mortality and frequently significant economic implications. Often, there is a lack or shortfall of effective prophylaxis and diagnostic capabilities. Research towards their development, together w...
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| Format: | Doctoral or Postdoctoral Thesis |
| Language: | unknown |
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University of Westminster
2017
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| Online Access: | https://westminsterresearch.westminster.ac.uk/item/q4yzx/the-study-of-highly-pathogenic-emerging-zoonotic-virus-envelope-proteins-through-pseudotyped-virus-generation https://westminsterresearch.westminster.ac.uk/download/e9bd989d7ac8fa1e4c82df0b7597a78d4eac173797d27a5b5cc42228c1afbfaa/7252413/Bentley_Emma_thesis.pdf https://doi.org/10.34737/q4yzx |
| Summary: | Emerging zoonotic viruses pose an increasing threat, causing outbreaks with high rates of morbidity and mortality and frequently significant economic implications. Often, there is a lack or shortfall of effective prophylaxis and diagnostic capabilities. Research towards their development, together with improved surveillance activities are high priority activities to prepare and respond to outbreak threats. Yet handling these viruses commonly requires high containment levels. This can be circumvented by the use of replication defective pseudotyped viruses (PVs), incorporating the viral envelope protein of interest which constitutes the primary surface antigen. This permits the serological detection of neutralising antibodies without the need to handle live virus, as well as other viral entry studies. Hence, PVs are increasingly proving to be a valuable tool for emerging virus research. The aim of this study was to exploit novelties in the unique flexibility of the PV platform to allow the serological assessment of emerging viruses and evaluate technical aspects towards standardisation. Current prophylaxis provides robust protection against rabies virus, yet only confers limited protection against other lyssavirus species, which have a near 100% fatality rate. It is thought protection is afforded against isolates of phylogroup I rabies virus, yet there is limited biological data for the Arctic-like rabies virus (AL RABV) lineage which is endemic across the Middle East and Asia. Although other lyssaviruses pseudotype efficiently, titres of AL RABV PV were low. Within this study, high titre PV was produced by constructing chimeric envelope proteins, splicing the AL RABV ecto-transmembrane domain with the cytoplasmic domain of vesicular stomatitis virus. Comparisons showed this did not alter the serological profile of the AL RABV and they were effectively neutralised by vaccines and antivirals. It could therefore be concluded that they do not pose a significant public health risk. However it is recognised broadly ... |
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