University of Southern Mississippi
Development of an Attenuated Zika Virus by Editing the 5’ Untranslated Region
Abstract
dc:description.abstract<p>Zika Virus (ZIKV) is a mosquito-transmitted flavivirus that usually causes no symptoms to mild febrile in humans, and it has been regarded as an insignificant pathogen to public health. However, recent outbreaks of ZIKV infection have revealed that ZIKV can cause severe neurological effects in adults, such as Guillain-Barre Syndrome (GBS), and in infants whose mothers acquired the virus during pregnancy, causing Congenital Zika Syndrome (CZS). Currently, no approved vaccine is available and there is a critical need to develop an effective and safe vaccine. While most vaccine developmental strategies target the viral prM-E protein of ZIKV, we aimed to create an attenuated ZIKV by inserting several different nucleotide lengths into the 5’ untranslated region (UTR) of the viral genome. We generated a viable mutated ZIKV virus (Z7) was after inserting a 50-nt sequence into the 5’UTR. We then characterized Z7 by comparing growth kinetics <em>in vivo</em> replication by using qPCR and immunostaining assays in cell cultures. We also measured the infectivity and immunogenicity of Z7 in <em>Ifnar1<sup>-/-</sup></em>mice. We found that this mutated virus developed a lower viremia compared to WT ZIKV control but induced a similar level of antibody response. Importantly, one dose of Z7 inoculation can protect the mice from a secondary high dose of ZIKV infection in <em>Ifnar1<sup>-/-</sup></em>mice. Together, these results suggest that we have successfully developed an attenuated ZIKV strain, which induces protective immune responses against ZIKV infection in mice.</p>
Degree
thesis:*- Name thesis:degree_name
- Master of Science (MS)
- Level thesis:degree_level
- Masters Thesis
- Year dc:date.available
- 2020
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Thompson, E. Ashley
- Contributors dc:contributor
-
- Dr. Fengwei Bai
- Dr. Shahid Karim
- Dr. Alex Flynt
Subjects
dc:subject × 8Identifiers
dc:identifier.*- Repository record dc:identifier
- https://aquila.usm.edu/masters_theses/739
- OAI identifier oai:identifier
- oai:aquila.usm.edu:masters_theses-1766