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| Author(s): |
Victória Thomazelli Garcia
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2023-04-13 |
| Examining board members: |
Luiz Tadeu Moraes Figueiredo;
Gustavo Olszanski Acrani;
Edison Luiz Durigon
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| Advisor: | Luiz Tadeu Moraes Figueiredo |
| Abstract | |
Among the Flavivirus in Brazil are included the arboviruses Cacipacoré (CPCV), Saint Louis Encephalitis (SLEV), 17DD Yellow Fever vaccine (YFV17DD), Ilhéus (ILHV) and Zika (ZIKV). These viruses cause human infections and some cause serious illness. In the first part of this Dissertation, we studied the cellular tropism of some Flavivirus from Brazil. We characterized the tropism of CPCV, ILHV, SLEV, YFV17DD and ZIKV by infection of cell tissues from different organs, identifying new susceptible cell lineages. Thus, we evaluated the susceptibility of human colorectal adenocarcinoma cells (Caco-2), human lung adenocarcinoma cells (Calu-3), Aedes albopictus larval cells (C6/36), human embryonic kidney cells (HEK293T) , human cervical adenocarcinoma cell (HeLa), human umbilical vein endothelial cells (HUVEC), human glioblastoma cells (U251-MG) and African green monkey kidney cells (Vero CCL81 and Vero E6), seeking to understand the pathophysiology of human infections related to tropisms by cells of different tissues. We observed that CPCV, ILHV, SLEV, YFV17DD and ZIKV Flavivirus infected in vitro cells of intestinal, epithelial, pulmonary, renal, uterine cervical and neuronal origin, except for YFV17DD in renal cells. CPCV, ILHV and ZIKV showed tropism for nervous tissue cells, which may be relevant in the pathogenesis of their human infections. Vero CCL81, HUVEC and Caco-2 cells were more susceptible to the viruses studied and can be routinely used for their amplification. In the second part of the Dissertation, considering the absence of treatment and vaccines against the Zika virus, which causes epidemics and infection related to the development of Guillain-Barré Syndrome and Congenital Zika Syndrome, we decided to construct a 17D Yellow Fever vaccine virus and a recombinant of this virus including ZIKV proteins. Thus, using the CPER technique, we constructed infectious clones of YFV17D and a chimeric recombinant virus with the YFV17D genome including the ZIKV prM and E proteins. The work was successful because it allowed obtaining the YFV17D virus and a YFV17DZIKV recombinant, the main objective of the work. However, the viruses obtained were not stable, which requires new interventions so that YFV17DZIKV can become a vaccine candidate. (AU) | |
| FAPESP's process: | 19/10565-1 - Development of a recombinant chimeric vaccine against Zika Virus |
| Grantee: | Victória Thomazelli Garcia |
| Support Opportunities: | Scholarships in Brazil - Master |