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- Genre: Masters Thesis
Description
ABSTRACT In terms of prevalence, human suffering and costs dengue infections are the most important arthropod-borne viral disease worldwide. Dengue virus (DENV) is a mosquito-borne flavivirus and the etiological agent of dengue fever and dengue hemorrhagic fever. Thus, development of a safe and efficient vaccine constitutes an urgent necessity. Besides the traditional strategies aim at generating immunization options, the usage of viral vectors to deliver antigenic stimulus in order to elicit protection are particularly attractive for the endeavor of a dengue vaccine. The viral vector (MVvac2) is genetically equivalent to the currently used measles vaccine strain Moraten, which adds practicality to my approach. The goal of the present study was to generate a recombinant measles virus expressing structural antigens from two strains of DENV (DENV2 and DENV4) The recombinant vectors replication profile was comparable to that of the parental strain and expresses either membrane bound or soluble forms of DENV2 and DENV4 E glycoproteins. I discuss future experiments in order to demonstrate its immunogenicity in our measles-susceptible mouse model.
ContributorsAbdelgalel, Rowida (Author) / Reyes del Valle, Jorge (Thesis advisor) / Hogue, Brenda (Committee member) / Frasch, Wayne D (Committee member) / Arizona State University (Publisher)
Created2013
Description
Human Papillomavirus (HPV) is the most commonly transmitted STI and isresponsible for an estimated 5% of cancer cases worldwide. HPV infection is implicated
in 70% of cervical cancer incidence and is also responsible for a variety of oropharyngeal
and anogenital cancers. While vaccination has greatly reduced the cervical cancer
burden in developed countries, HPV infection remains high in developing countries due
to high cost and poor access to healthcare. Several studies have highlighted the
presence of anti-HPV antibodies following infection and their potential use as
biomarkers for developing novel screening methods. Progression from initial infection to
cancer is slow, thus presenting an opportunity for effective screening programs.
Biomarker screening is an important area of cancer detection and Lateral Flow Assays
(LFA) are a low cost, easy to use alternative to other screening methods that require
extensive training and laboratory space. Therefore, this project proposes as a hypothesis
that the development of an LFA screening for HPV specific IgG can provide clinically
relevant data for the early detection of cervical dysplasia. This project adapts an LFA in a
multiplexed format for fluorescence-based serologic detection of HPV specific IgG in
patient plasma.
ContributorsJohns, William (Author) / Anderson, Karen (Thesis advisor) / Lake, Douglas (Committee member) / Hogue, Brenda (Committee member) / Arizona State University (Publisher)
Created2023
Description
Z-DNA binding protein 1 (ZBP1) is an interferon-inducible protein that plays a crucial role in antiviral defense by recognizing Z-form nucleic acid (Z-NA), a left-handed conformer of double-stranded DNA/RNA. When ZBP1 binds to Z-NA, it can trigger programmed cell death pathways, including apoptosis and necroptosis, in collaboration with receptor interacting protein kinases 1 and 3 (RIPK1 and RIPK3). Z-NA positive viruses including poxviruses and influenza A virus (IAV) activate ZBP1-dependent cell death during replication. Little is known whether ZBP1 plays any role during Z-NA negative virus infection. Doxycycline-inducible A549 ACE2 Tet-On cells were constructed to express ZBP1 and were infected with Z-NA negative viruses. ZBP1-expressing cells infected with Sindbis virus (SINV), La Crosse virus (LACV), Vesicular stomatitis virus (VSV) and human coronavirus OC43 (hCoV-OC43) underwent extensive cell death, which could be rescued by a caspase inhibitor but not by JAK1/2 or RIPK1 kinase inhibitors. However, cell death was not observed upon Zika virus (ZIKV), Encephalomyocarditis virus (EMCV), Chikungunya virus (CHKV) or human coronavirus 229E (hCoV-229E) infection. ZBP1 expression did not impact the replication of all tested viruses. In addition, ZBP1-mediated cell death during infection depends on the Zα2 and RHIM1 domains and partially on the C-terminal domain. These findings suggest that Z-NA can be detected by the Zα2 domain to initiate cell death pathways during infection with some Z-NA negative viruses and that the RHIM1/C-terminal domains are necessary for ZBP1-induced cell death. Further research is needed to determine the Z-NA ligand and the precise mechanism of ZBP1-mediated antiviral responses and how they can be exploited for the development of novel antiviral therapies.
ContributorsLa Rosa, Bruno Andres (Author) / Li, Yize (Thesis advisor) / Jacobs, Bertram (Committee member) / Hogue, Brenda (Committee member) / Arizona State University (Publisher)
Created2023