Banca de QUALIFICAÇÃO: KEYLA SILVA NOBRE PIRES

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : KEYLA SILVA NOBRE PIRES
DATE: 11/06/2021
TIME: 09:00
LOCAL: Videoconferência - Google meet
TITLE:

ZIKA VIRUS PLACENTAL INFECTION: SIGNALING PATHWAY INVESTIGATION AND AFFECTED CELL FUNCTIONS

KEY WORDS:

Zika virus; Congenital Infection; Interferon; Placenta.

PAGES: 82
BIG AREA: Ciências Biológicas
AREA: Imunologia
SUMMARY:

Introduction: The Zika Virus (ZIKV) is considered a major public health problem, due to its ability to cross the placental barrier and infect the fetus, causing the Congenital Zika Virus Syndrome. Although, despite the ZIKV epidemics have ceased, the infection still deserves great attention, as it generates a disease that involves public spending in the short, medium and long term and that despite the scientific efforts made in recent years, it still does not have biomarkers, or known prophylaxis, research on viral pathogenesis during pregnancy is of great relevance, which can provide important information and targets that can be targeted therapeutically, preventing the passage of ZIKV through the placenta. Objective: To investigate the immunological and molecular aspects associated with the pathophysiology of gestational infection by ZIKV in different experimental models. Methods: HTR-8/SVneo cells derived from the first trimester of gestation, primary culture of extravillous cytotrophoblast (EVT) cells  and placental explants from term pregnancies were infected with an African strain (MR766) and an Asian strain (PE243) of the ZIKV and the immune response was analyzed, through the analysis of the production of genes and cytokines, as well as activation of specific molecular pathways. Results: Placental explants were infected only with the PE243 strain and showed increased IFN-α gene expression (p < 0.05), as well as IL-6 (p < 0.05) and IL-8 (p < 0.05), although no change in IFN secretion has been found. HTR-8/SVneo cells were infected by both strains (72.2% for MR766 and 80.2% for PE243), but showed no changes in gene expression or IFN secretion. While EVT cells were also infected with both strains (63.8% for MR766 and 66.5% for PE243), but showed increased secretion of IFN-α2 (p < 0.0005), IFN-λ1 (p < 0.01) and IL-6 (p < 0.01) after infection by PE243, and only an increase in IFN-λ1 (p < 0.05) after infection by MR766. Signaling by the analyzed molecules differed only in infection by PE243, which increased the expression of p-IRF3 (p < 0.05) and IRF9 (p < 0.05), while p-STAT-2 remained unchanged after infection with both strains. Conclusions: The response to ZIKV is different at different gestational ages and depending on the viral strain. At the end of pregnancy, EVT cells differ from other models, producing some IFN and maintaining active antiviral response pathways, which can make it difficult for the virus to surpass the placenta and infect the fetus.

BANKING MEMBERS:
Presidente - 2151027 - ALEXANDRE URBAN BORBELY
Interna - 2022362 - ANA CATARINA REZENDE LEITE
Externo à Instituição - RAFAEL BRITO DA SILVA - UFF