Investigação das alterações na expressão dos HERVs, expressão de interleucinas e fatores da resposta imune em células de linhagens placentárias associadas à infecção pelo Zika vírus.
Data
2020-12-08
Autores
Costa, Anderson Luís da 
Orientadores
Janini, Luís Mário Ramos
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
O Zika vírus é um vírus de genoma RNA de polaridade positiva, que possui duas variantes principais: Africana e Asiática. Em julho de 2015, o Brasil notificou a associação entre a infecção pelo ZIka vírus e a síndrome de Guillain-Barré. Já em outubro de 2015, o Brasil notificou a associação entre a infecção pelo Zika vírus e a microcefalia. Como a microcefalia é uma sequela permanente que ocorre durante a gestação, alguns estudos têm avaliado o ambiente imune da placenta na presença de infecção viral. O genoma humano é constituído, entre outros componentes, por sequências retrovirais completas ou degeneradas, denominadas retrovírus endógenos (ERVs, do inglês endogenous retroviruses). Os retrovírus endógenos humanos (HERVs) têm características semelhantes às dos retrovírus exógenos, não sendo, contudo, infecciosos. Eles são transmitidos verticalmente como DNA proviral para o genoma de células germinativas. Os HERVs têm sido associados a muitas doenças complexas, podendo incluir a microcefalia e outros distúrbios neurológicos. A placenta possui atividade aumentada de HERVS, incluindo os HERV W e FRD, ambos responsáveis pela produção das proteínas sincitina 1 e 2, respectivamente. Esses dois HERVS apresentam atividades imunoreguladoras, assim como o HERV 3. No entanto, pouco se sabe sobre a relação Placenta-HERVs-ZIKV, assim, investigar as alterações nas expressões dos HERVs e genes da resposta imune em células de linhagens placentárias consiste em uma pergunta bastante relevante. O objetivo do presente trabalho foi analisar a modulação do ambiente imune em linhagens placentárias infectadas in vitro com Zika vírus. Para isso, análises dos dados foram realizadas por medidas estatísticas sobre os valores de expressões dos mRNA dos HERVs e de componentes da resposta imune das células de linhagem placentárias. Os resultados obtidos mostraram que os HERVS W, FRD e 3 apresentaram alterações significativas quando relacionadas entre as células Bewo e HTR8, infectadas e não infectadas com os Zika vírus MR7-66 baixa passagem e com o Zika vírus IEC. Os nossos achados demonstraram que a expressão diferencial dos HERVs nas células de linhagem placentárias parece influenciar na expressão de fatores da resposta imune nessas células, o que indica uma possível alteração na expressão dos HERVs.
Zika vírus is a positive-strand RNA genome virus with two genotypes, African and Asian. In July 2015, a link between the Zika virus infection and Guillain-Barré syndrome (GBS) was recognized in Brazil, 3 months later a link between Zika virus infection and microcephaly was noticed. Since microcephaly is a permanent damage that occurs during pregnancy, some studies have evaluated the immune environment of the placenta in the presence of viral infection. Among other things, the human genome is composed of complete or degenerate retroviral sequences called endogenous retroviruses (ERVs, from endogenous retroviruses). Human endogenous retroviruses (HERVs) carry characteristics similar to those of exogenous retroviruses, however, they are not infectious. They are transmitted vertically as proviral DNA in the germ cell genome. HERVs have been associated with many complex diseases, including microcephaly and other neurological disorders. The placenta has increased activity of HERVs, which include HERV-W and HERV-FRD, both produce Syncytin-1 and Syncytin-2 respectively. These two HERVs have immunoregulatory activities as well as ERV3. Little is known about the connection between the placenta, HERVs and Zika Virus, thus investigating changes in the expressions of HERVs and immune response genes in cells of placental lineages is very important. The research goal was to analyze the modulation of the immune environment in placental lines infected in vitro with Zika vírus. Data analyses were performed using statistical measures on the expression values of the HERVs, mRNAs and components of immune response of placental lineage cells. They were then, compared to the expression of their respective controls - absence of Zika vírus infection. Final outcome: HERV-W, HERV-FRD and ERV3 showed significant changes when compared to BeWo and HTR8 cells, infected and not infected with the Zika vírus MR766 Low passage (African lineage) and the Zika vírus IEC (Asian lineage). The findings reveal that the differential expression of HERVs in cells of placental strains seems to influence the expression of immune response factors in these cells. That is an indication of a possible change in the viral infection profile.
Zika vírus is a positive-strand RNA genome virus with two genotypes, African and Asian. In July 2015, a link between the Zika virus infection and Guillain-Barré syndrome (GBS) was recognized in Brazil, 3 months later a link between Zika virus infection and microcephaly was noticed. Since microcephaly is a permanent damage that occurs during pregnancy, some studies have evaluated the immune environment of the placenta in the presence of viral infection. Among other things, the human genome is composed of complete or degenerate retroviral sequences called endogenous retroviruses (ERVs, from endogenous retroviruses). Human endogenous retroviruses (HERVs) carry characteristics similar to those of exogenous retroviruses, however, they are not infectious. They are transmitted vertically as proviral DNA in the germ cell genome. HERVs have been associated with many complex diseases, including microcephaly and other neurological disorders. The placenta has increased activity of HERVs, which include HERV-W and HERV-FRD, both produce Syncytin-1 and Syncytin-2 respectively. These two HERVs have immunoregulatory activities as well as ERV3. Little is known about the connection between the placenta, HERVs and Zika Virus, thus investigating changes in the expressions of HERVs and immune response genes in cells of placental lineages is very important. The research goal was to analyze the modulation of the immune environment in placental lines infected in vitro with Zika vírus. Data analyses were performed using statistical measures on the expression values of the HERVs, mRNAs and components of immune response of placental lineage cells. They were then, compared to the expression of their respective controls - absence of Zika vírus infection. Final outcome: HERV-W, HERV-FRD and ERV3 showed significant changes when compared to BeWo and HTR8 cells, infected and not infected with the Zika vírus MR766 Low passage (African lineage) and the Zika vírus IEC (Asian lineage). The findings reveal that the differential expression of HERVs in cells of placental strains seems to influence the expression of immune response factors in these cells. That is an indication of a possible change in the viral infection profile.